Difference between revisions of "Editing test page 2"

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m
m
Tag: visualeditor
 
(20 intermediate revisions by 4 users not shown)
Line 1: Line 1:
−
<span id="BackToTop"></span>
+
==Carboplatin & Paclitaxel (CP) {{#subobject:3a6h8q|Regimen=1}}==
−
<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
+
CP: '''<u>C</u>'''arboplatin & '''<u>P</u>'''aclitaxel
−
[[#top|Back to Top]]
+
<div class="toccolours" style="background-color:#eeeeee">
−
</div>
+
===Regimen {{#subobject:1yg1q7|Variant=1}}===
−
{{#lst:Section editor transclusions|breast}}
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Breast_cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Breast cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''
 
−
*'''Note: this page contains regimens which were not tested in biomarker-specific populations. The following links will take you to biomarker-specific subpages:'''  
 
−
*<big>Regimens for [[Breast_cancer,_ER-positive|'''ER/PR positive breast cancer are here''']]</big>.
 
−
*<big>Regimens for [[Breast_cancer,_HER2-positive|'''HER2 positive breast cancer are here''']]</big>.
 
−
*<big>Regimens for [[Breast cancer, ER and HER2 co-expressing|'''ER/HER2 co-expressing ("double positive") breast cancer are here''']]</big>.
 
−
*<big>Regimens for [[Breast_cancer,_triple_negative|'''Triple negative breast cancer (TNBC) are here''']]</big>.
 
−
*<big>Regimens for [[Breast_cancer,_BRCA-mutated|'''BRCA-mutated breast cancer are here''']]</big>.
 
−
*<big>Regimens for [[Breast cancer, PIK3CA-mutated|'''PIK3CA-mutated breast cancer are here''']]</big>.
 
−
*<big>Regimens for [[CNS_carcinoma|'''CNS metastases are here''']]</big>.
 
−
*''Because docetaxel and paclitaxel are both often abbreviated as "T," we try to always make clear in the regimen name which agent is being used. For sequential protocols, we use "T" for paclitaxel and "D" for docetaxel; e.g., [[#AC-T|AC-T]] and [[#AC-D|AC-D]].''
 
−
{| class="wikitable" style="float:right; margin-right: 5px;"
 
−
|-
 
−
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
−
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
−
|}
 
−
{{TOC limit|limit=3}}
 
−
 
 
−
=Guidelines=
 
−
==[https://www.asco.org/ ASCO]==
 
−
*'''2021:''' Burstein et al. [https://doi.org/10.1200/jco.21.01392 Endocrine Treatment and Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: ASCO Guideline Update]
 
−
*'''2021:''' Moy et al. [https://doi.org/10.1200/jco.21.01374 Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor-Negative: ASCO Guideline Update]
 
−
*'''2021:''' Korde et al. [https://doi.org/10.1200/jco.20.03399 Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline]
 
−
*'''2020:''' Denduluri et al. [https://doi.org/10.1200/jco.20.02510 Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update]
 
−
*'''2020:''' Hassett et al. [https://doi.org/10.1200/jco.19.03120 Management of Male Breast Cancer: ASCO Guideline] [https://pubmed.ncbi.nlm.nih.gov/32058842 PubMed]
 
−
*'''2016:''' Burstein et al. [https://doi.org/10.1200/JCO.2015.65.9573 Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline update on ovarian suppression] [https://pubmed.ncbi.nlm.nih.gov/26884586 PubMed]
 
−
===Older===
 
−
*'''2018:''' Denduluri et al. [https://doi.org/10.1200/JCO.2018.78.8604 Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO clinical practice guideline focused update] [https://pubmed.ncbi.nlm.nih.gov/29787356 PubMed]
 
−
*'''2016:''' Harris et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933134/ Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline]
 
−
*'''2015:''' van Poznak et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478102/ Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology Clinical practice guideline]
 
−
*'''2014:''' Partridge et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076042/ Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2-negative (or unknown) advanced breast cancer: American Society of Clinical Oncology Clinical Practice Guideline]
 
−
 
 
−
==ASCO/CCO==
 
−
*'''2022:''' Eisen et al. [https://doi.org/10.1200/jco.21.02647 Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update]
 
−
===Older===
 
−
*'''2017:''' Van Poznak et al. [https://doi.org/10.1200/JCO.2017.75.4614 Role of bone-modifying agents in metastatic breast cancer: an American Society of Clinical Oncology–Cancer Care Ontario focused guideline update]
 
−
 
 
−
==[http://www.esmo.org/ ESMO]==
 
−
*'''2021:''' Gennari et al. [https://www.annalsofoncology.org/article/S0923-7534(21)04498-7 ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer]
 
−
*'''2019:''' Cardoso et al. [https://academic.oup.com/annonc/article/30/8/1194/5499075 Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
===Older===
 
−
*'''2015:''' Senkus et al. [https://www.esmo.org/Guidelines/Breast-Cancer/Primary-Breast-Cancer Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
 
 
−
==ESO/ESMO==
 
−
*'''2020:''' Paluch-Shimon et al. [https://doi.org/10.1016/j.annonc.2020.03.284 ESO–ESMO 4th International Consensus Guidelines for Breast Cancer in Young Women (BCY4)]
 
−
*'''2018:''' Cardoso et al. [https://academic.oup.com/annonc/article/29/8/1634/5055519 4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)]
 
−
===Older===
 
−
*'''2017:''' Cardoso et al. [http://www.thebreastonline.com/article/S0960-9776(16)30183-7 3rd ESO-ESMO International consensus guidelines for advanced breast cancer (ABC3)] [https://pubmed.ncbi.nlm.nih.gov/27927580 PubMed]
 
−
*'''2014:''' Cardoso et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176456/ ESO-ESMO 2nd International consensus guidelines for advanced breast cancer (ABC2)]
 
−
*'''2012:''' Cardoso et al. [https://www.thebreastonline.com/article/S0960-9776(12)00062-8 1st International consensus guidelines for advanced breast cancer (ABC 1)]
 
−
 
 
−
==EUSOMA/SIOG==
 
−
*'''2021:''' Biganzoli et al. [https://doi.org/10.1016/s1470-2045(20)30741-5 Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European Society of Breast Cancer Specialists (EUSOMA) and the International Society of Geriatric Oncology (SIOG)]
 
−
===Older===
 
−
*'''2012:''' Biganzoli et al. [https://doi.org/10.1016/s1470-2045(11)70383-7 Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA)]
 
−
*'''2007:''' Wildiers et al. [https://doi.org/10.1016/s1470-2045(07)70378-9 Management of breast cancer in elderly individuals: recommendations of the International Society of Geriatric Oncology]
 
−
 
 
−
==KSMO/ESMO==
 
−
*'''2020:''' Park et al. [https://doi.org/10.1016/j.annonc.2020.01.008 Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with early breast cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS]
 
−
 
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf NCCN Guidelines - Breast Cancer]
 
−
 
 
−
== St Gallen Breast Guidelines ==
 
−
*'''2021:''' Burstein et al. [https://doi.org/10.1016/j.annonc.2021.06.023 Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021]
 
−
===Older===
 
−
*'''2019:''' Burstein et al. [https://academic.oup.com/annonc/article/30/10/1541/5543097 Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019]
 
−
*'''2017:''' Curigliano et al. [https://pubmed.ncbi.nlm.nih.gov/28838210 St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2017]
 
−
*'''2015:''' Coates et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511219/ Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015]
 
−
 
 
−
=Neoadjuvant chemotherapy, sequential protocols=
 
−
 
 
−
==AC-D {{#subobject:hzzn67|Regimen=1}}==
 
−
 
 
−
AC-D: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide followed by '''<u>D</u>'''ocetaxel
 
−
===Regimen variant #1, 60/600/75 {{#subobject:80y4x4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 20%"|Dates of enrollment
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7251809/ Kim et al. 2020 (NEST)]
+
|[https://doi.org/10.1056/nejmoa2202170 Forde et al. 2022 (CheckMate 816)]
−
|2012-2014
+
|2017-2019
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer,_ER-positive#Goserelin_.26_Tamoxifen|Goserelin & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior clinical response
 
−
|-
 
−
|}
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 4: 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, T portion====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycles 5 to 8: 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===Regimen variant #2, 60/600/100 {{#subobject:80xo14|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.2003.12.005 Bear et al. 2003 (NSABP B-27)]
 
−
|rowspan=2|1995-2000
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29|AC]]
 
−
| style="background-color:#1a9850" |Superior pCR rate
 
−
|-
 
−
|2. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29|AC]], then surgery, then [[#Docetaxel_monotherapy|T]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.05.078 von Minckwitz et al. 2005 (GeparDuo)]
 
−
|1999-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Dose-dense_Docetaxel_.26_Doxorubicin_.28AT.29_88|ddAT]]
 
−
| style="background-color:#1a9850" |Superior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 4: 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, T portion====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycles 5 to 8: 100 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''NSABP B-27:''' Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N; National Surgical Adjuvant Breast and Bowel Project. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003 Nov 15;21(22):4165-74. Epub 2003 Oct 14. [https://doi.org/10.1200/JCO.2003.12.005 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14559892 PubMed] NCT00002707
 
−
## '''Update:''' Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006 May 1;24(13):2019-27. Epub 2006 Apr 10. [https://doi.org/10.1200/JCO.2005.04.1665 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16606972 PubMed]
 
−
## '''Pooled update:''' Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. [https://doi.org/10.1200/JCO.2007.15.0235 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18258986 PubMed]
 
−
# '''GeparDuo:''' von Minckwitz G, Raab G, Caputo A, Schütte M, Hilfrich J, Blohmer JU, Gerber B, Costa SD, Merkle E, Eidtmann H, Lampe D, Jackisch C, du Bois A, Kaufmann M; [[Study_Groups#GBG|GBG]]. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol. 2005 Apr 20;23(12):2676-85. [https://doi.org/10.1200/JCO.2005.05.078 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15837982 PubMed] NCT00793377
 
−
# '''NEST:''' Kim HJ, Noh WC, Lee ES, Jung YS, Kim LS, Han W, Nam SJ, Gong GY, Kim HJ, Ahn SH. Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with oestrogen receptor-positive and HER2-negative, lymph node-positive breast cancer. Breast Cancer Res. 2020 May 27;22(1):54. [https://doi.org/10.1186/s13058-020-01288-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7251809/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32460816/ PubMed] NCT01622361
 
−
 
 
−
==AC-T {{#subobject:633n67|Regimen=1}}==
 
−
 
 
−
AC-T: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide followed by '''<u>T</u>'''axol (Paclitaxel)
 
−
 
 
−
===Regimen variant #1, 5 x 4 {{#subobject:80c6e6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068051/ Ellis et al. 2011 (SWOG 0012)]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#AC-T|AC-T]]; daily cyclophosphamide
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 5: 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 5: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 6 to 9: 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
'''21-day cycle for 9 cycles'''
 
−
 
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''SWOG 0012:''' Ellis GK, Barlow WE, Gralow JR, Hortobagyi GN, Russell CA, Royce ME, Perez EA, Lew D, Livingston RB. Phase III comparison of standard doxorubicin and cyclophosphamide versus weekly doxorubicin and daily oral cyclophosphamide plus granulocyte colony-stimulating factor as neoadjuvant therapy for inflammatory and locally advanced breast cancer: SWOG 0012. J Clin Oncol. 2011 Mar 10;29(8):1014-21. Epub 2011 Jan 10. [https://doi.org/10.1200/JCO.2009.27.6543 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068051/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21220618 PubMed] NCT00016406
 
−
 
 
−
==D-AC {{#subobject:1216fd|Regimen=1}}==
 
−
D-AC: '''<u>D</u>'''ocetaxel followed by '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide
 
−
===Regimen {{#subobject:7377be|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401076/ Bear et al. 2012 (NSABP B-40)]
 
−
|rowspan=2|2007-2010
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#D-AC.2BBev|D-AC+Bev]]<br>2. [[#TG-AC.2BBev_99|TG-AC+Bev]]<br>3. [[#TX-AC.2BBev_99|TX-AC+Bev]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior pCR rate
 
−
|-
 
−
|4. [[#TG-AC_.28Docetaxel.29_99|TG-AC]]<br>5. [[#TX-AC_.28Docetaxel.29_99|TX-AC]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycles 1 to 4: 75 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 5 to 8: 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|surgery]]
 
−
 
 
−
===References===
 
−
# '''NSABP B-40:''' Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. [https://doi.org/10.1056/NEJMoa1111097 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401076/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22276821 PubMed] NCT00408408
 
−
## '''Update:''' Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. [https://doi.org/10.1016/S1470-2045(15)00041-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624323/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26272770 PubMed]
 
−
 
 
−
==D-AC+Bev {{#subobject:23b667|Regimen=1}}==
 
−
D-AC+Bev: '''<u>D</u>'''ocetaxel followed by '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide, with '''<u>Bev</u>'''acizumab
 
−
===Regimen {{#subobject:d65a23|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401076/ Bear et al. 2012 (NSABP B-40)]
 
−
|rowspan=2|2007-2010
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#D-AC|D-AC]]<br>2. [[#TG-AC_.28Docetaxel.29_99|TG-AC]]<br>3. [[#TX-AC_.28Docetaxel.29_99|TX-AC]]
 
−
|style="background-color:#91cf60"|Seems to have superior pCR rate
 
−
|-
 
−
|4. [[#TG-AC.2BBev_99|TG-AC+Bev]]<br>5. [[#TX-AC.2BBev_99|TX-AC+Bev]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycles 1 to 4: 75 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 5 to 8: 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] as follows:
 
−
**Cycles 1 to 6: 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|surgery]]
 
−
 
 
−
===References===
 
−
# '''NSABP B-40:''' Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. [https://doi.org/10.1056/NEJMoa1111097 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401076/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22276821 PubMed] NCT00408408
 
−
## '''Update:''' Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. [https://doi.org/10.1016/S1470-2045(15)00041-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624323/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26272770 PubMed]
 
−
 
 
−
==D-FEC {{#subobject:7ygn67|Regimen=1}}==
 
−
 
 
−
D-FEC: '''<u>D</u>'''ocetaxel followed by '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide
 
−
===Regimen {{#subobject:5b038d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)70137-3 Earl et al. 2015 (ARTemis)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#D-FEC.2BBev|D-FEC+Bev]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycles 1 to 3: 100 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, FEC portion====
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 4 to 6: 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 4 to 6: 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 4 to 6: 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''ARTemis:''' Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Abraham J, Thomas J, Provenzano E, Hughes-Davies L, Gounaris I, McAdam K, Chan S, Ahmad R, Hickish T, Houston S, Rea D, Bartlett J, Caldas C, Cameron DA, Hayward L; ARTemis Investigators. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):656-66. Epub 2015 May 11. [https://doi.org/10.1016/S1470-2045(15)70137-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25975632 PubMed] NCT01093235
 
−
 
 
−
==D-FEC+Bev {{#subobject:7ygn67|Regimen=1}}==
 
−
 
 
−
D-FEC+Bev: '''<u>D</u>'''ocetaxel followed by '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, with '''<u>Bev</u>'''acizumab
 
−
===Regimen {{#subobject:a2a6a4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)70137-3 Earl et al. 2015 (ARTemis)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#D-FEC|D-FEC]]
 
−
| style="background-color:#91cf60" |Seems to have superior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycles 1 to 3: 100 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, FEC portion====
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 4 to 6: 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 4 to 6: 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 4 to 6: 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] as follows:
 
−
**Cycles 1 to 4: 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''ARTemis:''' Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Abraham J, Thomas J, Provenzano E, Hughes-Davies L, Gounaris I, McAdam K, Chan S, Ahmad R, Hickish T, Houston S, Rea D, Bartlett J, Caldas C, Cameron DA, Hayward L; ARTemis Investigators. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):656-66. Epub 2015 May 11. [https://doi.org/10.1016/S1470-2045(15)70137-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25975632 PubMed] NCT01093235
 
−
 
 
−
==EC-D {{#subobject:8umauq|Regimen=1}}==
 
−
EC-D: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide followed by '''<u>D</u>'''ocetaxel
 
−
===Regimen {{#subobject:dat17g|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2009.23.8303 von Minckwitz et al. 2010 (GeparQuattro)]
 
−
|2005-NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#EC-TX_99|EC-TX]]<br>2. [[#EC-T-X_99|EC-T-X]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1111065 von Minckwitz et al. 2012 (GeparQuinto)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#EC-D.2BBev_88|EC-D+Bev]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 4: 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycles 5 to 8: 100 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
===References===
 
−
# '''GeparQuattro:''' von Minckwitz G, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, Bauerfeind I, Hilfrich J, Eidtmann H, Gerber B, Hanusch C, Kühn T, du Bois A, Blohmer JU, Thomssen C, Dan Costa S, Jackisch C, Kaufmann M, Mehta K, Untch M. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol. 2010 Apr 20;28(12):2015-23. Epub 2010 Mar 22. [https://doi.org/10.1200/JCO.2009.23.8303 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20308671 PubMed] NCT00288002
 
−
## '''Update:''' von Minckwitz G, Rezai M, Fasching PA, Huober J, Tesch H, Bauerfeind I, Hilfrich J, Eidtmann H, Gerber B, Hanusch C, Blohmer JU, Dan Costa S, Jackisch C, Paepke S, Schneeweiss A, Kümmel S, Denkert C, Mehta K, Loibl S, Untch M. Survival after adding capecitabine and trastuzumab to neoadjuvant anthracycline-taxane-based chemotherapy for primary breast cancer (GBG 40--GeparQuattro). Ann Oncol. 2014 Jan;25(1):81-9. Epub 2013 Nov 21. [https://doi.org/10.1093/annonc/mdt410 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24273046/ PubMed]
 
−
# '''GeparQuinto:''' von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. [https://doi.org/10.1056/NEJMoa1111065 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22276820 PubMed] NCT00567554
 
−
 
 
−
==EC-T {{#subobject:8um5th|Regimen=1}}==
 
−
EC-T: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide followed by '''<u>T</u>'''axol (Paclitaxel)
 
−
===Regimen {{#subobject:y9ca7g|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdq713 Untch et al. 2011 (PREPARE)]
 
−
|2002-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ddE-ddT-CMF_99|ddE-ddT-CMF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 4: 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 5 to 8: 175 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
===References===
 
−
# '''PREPARE:''' Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C, Lück HJ, Stickeler E, Urbaczyk H, Liedtke B, Beckmann MW, Salat C, Harbeck N, Müller V, Schmidt M, Hasmüller S, Lenhard M, Nekljudova V, Lebeau A, Loibl S, Fasching PA; Arbeitsgemeinschaft Gynäkologische Onkologie PREPARE investigators. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer--outcome on prognosis. Ann Oncol. 2011 Sep;22(9):1999-2006. Epub 2011 Mar 7. [https://doi.org/10.1093/annonc/mdq713 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21382868 PubMed] NCT00544232
 
−
 
 
−
==EC-ddT {{#subobject:3gjq8f|Regimen=1}}==
 
−
 
 
−
EC-ddT: '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide, followed by '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>T</u>'''axol (Paclitaxel)
 
−
===Regimen {{#subobject:da33qc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/S1470-2045(13)70554-0 Earl et al. 2013 (Neo-tAnGo)]
 
−
|rowspan=2|2005-2007
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#ddT-EC|ddT-EC]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior pCR rate
 
−
|-
 
−
|2. [[#EC-ddTG_99|EC-ddTG]]<br>3. [[#ddTG-EC_99|ddTG-EC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 4: 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 5 to 8: 175 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy, T portion====
 
−
*Primary G-CSF propyhylaxis not provided
 
−
 
 
−
'''21-day cycle for 4 cycles, then 14-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|surgery]]
 
−
 
 
−
===References===
 
−
# '''Neo-tAnGo:''' Earl HM, Vallier AL, Hiller L, Fenwick N, Young J, Iddawela M, Abraham J, Hughes-Davies L, Gounaris I, McAdam K, Houston S, Hickish T, Skene A, Chan S, Dean S, Ritchie D, Laing R, Harries M, Gallagher C, Wishart G, Dunn J, Provenzano E, Caldas C; Neo-tAnGo Investigators. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):201-12. Epub 2013 Dec 19. [https://doi.org/10.1016/S1470-2045(13)70554-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24360787 PubMed] NCT00070278
 
−
 
 
−
==nab-Paclitaxel-EC {{#subobject:8f6227|Regimen=1}}==
 
−
nab-Paclitaxel-EC: nab-Paclitaxel followed by '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide
 
−
===Regimen {{#subobject:fe2978|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(15)00542-2 Untch et al. 2016 (GeparSepto)]
 
−
|2012-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#T-EC|T-EC]]
 
−
| style="background-color:#1a9850" |Superior pCR rate
 
−
|-
 
−
|}
 
−
''Note: this is the dose after study amendment due to increased treatment discontinuation and sensory neuropathy.''
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] as follows:
 
−
**Cycles 1 to 4: 125 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 5 to 8: 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
===References===
 
−
# '''GeparSepto:''' Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kümmel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Darb-Esfahani S, Schmitt WD, Dan Costa S, Gerber B, Engels K, Nekljudova V, Loibl S, von Minckwitz G; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie—Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. Epub 2016 Feb 8. 2016 Mar;17(3):345-56. [https://doi.org/10.1016/s1470-2045(15)00542-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26869049 PubMed] NCT01583426
 
−
## '''Update:''' Furlanetto J, Jackisch C, Untch M, Schneeweiss A, Schmatloch S, Aktas B, Denkert C, Wiebringhaus H, Kümmel S, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Costa SD, Gerber B, Nekljudova V, Loibl S, von Minckwitz G. Efficacy and safety of nab-paclitaxel 125 mg/m(2) and nab-paclitaxel 150 mg/m(2) compared to paclitaxel in early high-risk breast cancer: results from the neoadjuvant randomized GeparSepto study (GBG 69). Breast Cancer Res Treat. 2017 Jun;163(3):495-506. Epub 2017 Mar 17. [https://doi.org/10.1007/s10549-017-4200-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28315068 PubMed]
 
−
# '''ETNA:''' Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA, Magazzù D, De Fato R, Valagussa P, Tusquets I. Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/HER2-negative breast cancer-the Evaluating Treatment with Neoadjuvant Abraxane (ETNA) trial: a randomized phase 3 clinical trial. JAMA Oncol. 2018 Mar 1;4(3):302-308. Epub 2018 Jan 11. [https://doi.org/10.1001/jamaoncol.2017.4612 link to original article] '''contains dosing details in manuscript''' [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5885830/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29327055 PubMed] NCT01822314
 
−
 
 
−
==T-AC {{#subobject:f5jq1b|Regimen=1}}==
 
−
 
 
−
T-AC: '''<u>T</u>'''axol (Paclitaxel), followed by '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide
 
−
===Regimen {{#subobject:759ubx|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5885830/ Gianni et al. 2018 (ETNA)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#nab-Paclitaxel-AC_99|nab-Paclitaxel-AC]]<br>2. [[#nab-Paclitaxel-EC|nab-Paclitaxel-EC]]<br>3. [[#nab-Paclitaxel-FEC_99|nab-Paclitaxel-FEC]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 1 to 4: 90 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 5 to 8: 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycle for 4 cycles, then 21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''ETNA:''' Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA, Magazzù D, De Fato R, Valagussa P, Tusquets I. Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/HER2-negative breast cancer-the Evaluating Treatment with Neoadjuvant Abraxane (ETNA) trial: a randomized phase 3 clinical trial. JAMA Oncol. 2018 Mar 1;4(3):302-308. Epub 2018 Jan 11. [https://doi.org/10.1001/jamaoncol.2017.4612 link to original article] '''contains dosing details in manuscript''' [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5885830/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29327055 PubMed] NCT01822314
 
−
 
 
−
==T-EC {{#subobject:f57gac|Regimen=1}}==
 
−
 
 
−
T-EC: '''<u>T</u>'''axol (Paclitaxel), followed by '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide
 
−
 
 
−
===Regimen variant #1, 80 mg/m<sup>2</sup> paclitaxel {{#subobject:c347uy|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(15)00542-2 Untch et al. 2016 (GeparSepto)]
 
−
|2012-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#nab-Paclitaxel-EC|nab-Paclitaxel-EC]]
 
−
| style="background-color:#d73027" |Inferior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 1 to 4: 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 5 to 8: 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===Regimen variant #2, 90 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:759920|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5885830/ Gianni et al. 2018 (ETNA)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#nab-Paclitaxel-AC_99|nab-Paclitaxel-AC]]<br>2. [[#nab-Paclitaxel-EC|nab-Paclitaxel-EC]]<br>3. [[#nab-Paclitaxel-FEC_99|nab-Paclitaxel-FEC]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 1 to 4: 90 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 5 to 8: 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycle for 4 cycles, then 21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''GeparSepto:''' Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kümmel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Darb-Esfahani S, Schmitt WD, Dan Costa S, Gerber B, Engels K, Nekljudova V, Loibl S, von Minckwitz G; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie—Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. Epub 2016 Feb 8. 2016 Mar;17(3):345-56. [https://doi.org/10.1016/s1470-2045(15)00542-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26869049 PubMed] NCT01583426
 
−
## '''Update:''' Furlanetto J, Jackisch C, Untch M, Schneeweiss A, Schmatloch S, Aktas B, Denkert C, Wiebringhaus H, Kümmel S, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Costa SD, Gerber B, Nekljudova V, Loibl S, von Minckwitz G. Efficacy and safety of nab-paclitaxel 125 mg/m(2) and nab-paclitaxel 150 mg/m(2) compared to paclitaxel in early high-risk breast cancer: results from the neoadjuvant randomized GeparSepto study (GBG 69). Breast Cancer Res Treat. 2017 Jun;163(3):495-506. Epub 2017 Mar 17. [https://doi.org/10.1007/s10549-017-4200-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28315068 PubMed]
 
−
# '''ETNA:''' Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA, Magazzù D, De Fato R, Valagussa P, Tusquets I. Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/HER2-negative breast cancer-the Evaluating Treatment with Neoadjuvant Abraxane (ETNA) trial: a randomized phase 3 clinical trial. JAMA Oncol. 2018 Mar 1;4(3):302-308. Epub 2018 Jan 11. [https://doi.org/10.1001/jamaoncol.2017.4612 link to original article] '''contains dosing details in manuscript''' [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5885830/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29327055 PubMed] NCT01822314
 
−
 
 
−
==ddT-EC {{#subobject:3gug1f|Regimen=1}}==
 
−
 
 
−
ddT-EC: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>T</u>'''axol (Paclitaxel), followed by '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide
 
−
===Regimen {{#subobject:cq33ad|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/S1470-2045(13)70554-0 Earl et al. 2013 (Neo-tAnGo)]
 
−
|rowspan=2|2005-2007
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#EC-ddT|EC-ddT]]
 
−
| style="background-color:#91cf60" |Seems to have superior pCR rate
 
−
|-
 
−
|2. [[#EC-ddTG_99|EC-ddTG]]<br>3. [[#ddTG-EC_99|ddTG-EC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 1 to 4: 175 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy, T portion====
 
−
*Primary G-CSF propyhylaxis not provided
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 5 to 8: 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''14-day cycle for 4 cycles, then 21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''Neo-tAnGo:''' Earl HM, Vallier AL, Hiller L, Fenwick N, Young J, Iddawela M, Abraham J, Hughes-Davies L, Gounaris I, McAdam K, Houston S, Hickish T, Skene A, Chan S, Dean S, Ritchie D, Laing R, Harries M, Gallagher C, Wishart G, Dunn J, Provenzano E, Caldas C; Neo-tAnGo Investigators. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):201-12. Epub 2013 Dec 19. [https://doi.org/10.1016/S1470-2045(13)70554-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24360787 PubMed] NCT00070278
 
−
 
 
−
==T-FAC {{#subobject:f5ccac|Regimen=1}}==
 
−
 
 
−
T-FAC: '''<u>T</u>'''axol (Paclitaxel), followed by '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
 
−
 
 
−
===Regimen variant #1, weekly paclitaxel for N0 disease {{#subobject:c3jgny|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.06.232 Green et al. 2005]
 
−
|1998-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#T-FAC|T-FAC]]; q3wk paclitaxel
 
−
| style="background-color:#91cf60" |Seems to have superior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 1 to 4: 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
====Chemotherapy, FAC portion====
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 5 to 8: 500 mg/m<sup>2</sup> IV once per day on days 1 & 4
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 5 to 8: 16.7 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 50 mg/m<sup>2</sup>)
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===Regimen variant #2, weekly paclitaxel for N+ disease {{#subobject:c3j1uy|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.06.232 Green et al. 2005]
 
−
|1998-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#T-FAC|T-FAC]]; q3wk paclitaxel
 
−
| style="background-color:#91cf60" |Seems to have superior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 1 to 4: 150 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 8, 15
 
−
 
 
−
====Chemotherapy, FAC portion====
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 5 to 8: 500 mg/m<sup>2</sup> IV once per day on days 1 & 4
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 5 to 8: 16.7 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 50 mg/m<sup>2</sup>)
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycle for 4 cycles, then 21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===Regimen variant #3, q3wk paclitaxel {{#subobject:7g1gny|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.06.232 Green et al. 2005]
 
−
|1998-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#T-FAC|T-FAC]]; weekly paclitaxel
 
−
| style="background-color:#fc8d59" |Seems to have inferior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 1 to 4: 225 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
 
 
−
====Chemotherapy, FAC portion====
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 5 to 8: 500 mg/m<sup>2</sup> IV once per day on days 1 & 4
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 5 to 8: 16.7 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 50 mg/m<sup>2</sup>)
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# Green MC, Buzdar AU, Smith T, Ibrahim NK, Valero V, Rosales MF, Cristofanilli M, Booser DJ, Pusztai L, Rivera E, Theriault RL, Carter C, Frye D, Hunt KK, Symmans WF, Strom EA, Sahin AA, Sikov W, Hortobagyi GN. Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol. 2005 Sep 1;23(25):5983-92. Epub 2005 Aug 8. [https://doi.org/10.1200/JCO.2005.06.232 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16087943 PubMed]
 
−
 
 
−
==T-FEC {{#subobject:ug89g8|Regimen=1}}==
 
−
 
 
−
T-FEC: '''<u>T</u>'''axol (Paclitaxel), followed by '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide
 
−
===Regimen variant #1, 80/500/100/500 {{#subobject:7g1gny|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2011.36.2079 Kelly et al. 2012 (MDACC ID01-580)]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TX-FEC_.28Docetaxel.29|TX-FEC]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of RFS
 
−
|-
 
−
|}
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 1 to 4: 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
====Chemotherapy, FEC portion====
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 5 to 8: 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 5 to 8: 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===Regimen variant #2, 90/600/90/600 {{#subobject:ugzzny|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5885830/ Gianni et al. 2018 (ETNA)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#nab-Paclitaxel-AC_99|nab-Paclitaxel-AC]]<br>2. [[#nab-Paclitaxel-EC|nab-Paclitaxel-EC]]<br>3. [[#nab-Paclitaxel-FEC_99|nab-Paclitaxel-FEC]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 1 to 4: 90 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
====Chemotherapy, FEC portion====
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 5 to 8: 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycle for 4 cycles, then 21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
<!-- Presented at the 44th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 30-June 3, 2008. -->
 
−
# '''MDACC ID01-580:''' Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU. Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol. 2012 Mar 20;30(9):930-5. Epub 2012 Feb 13. [https://doi.org/10.1200/JCO.2011.36.2079 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22331946 PubMed] NCT00050167
 
−
# '''ETNA:''' Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA, Magazzù D, De Fato R, Valagussa P, Tusquets I. Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/HER2-negative breast cancer-the Evaluating Treatment with Neoadjuvant Abraxane (ETNA) trial: a randomized phase 3 clinical trial. JAMA Oncol. 2018 Mar 1;4(3):302-308. Epub 2018 Jan 11. [https://doi.org/10.1001/jamaoncol.2017.4612 link to original article] '''contains dosing details in manuscript''' [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5885830/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29327055 PubMed] NCT01822314
 
−
 
 
−
=Neoadjuvant chemotherapy=
 
−
 
 
−
==Capecitabine & Docetaxel (TX) {{#subobject:9d7c10|Regimen=1}}==
 
−
 
 
−
TX: '''<u>T</u>'''axotere (Docetaxel) & '''<u>X</u>'''eloda (Capecitabine)
 
−
===Regimen {{#subobject:acc1b7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-007-9672-y Lee et al. 2007]
 
−
|2002-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29|AC]]
 
−
| style="background-color:#91cf60" |Seems to have superior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# Lee KS, Ro J, Nam BH, Lee ES, Kwon Y, Kwon HS, Chung KW, Kang HS, Kim EA, Kim SW, Shin KH, Kim SK. A randomized phase-III trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage II/III breast cancer. Breast Cancer Res Treat. 2008 Jun;109(3):481-9. Epub 2007 Jul 26. [https://doi.org/10.1007/s10549-007-9672-y link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17653851 PubMed]
 
−
 
 
−
==Cyclophosphamide & Doxorubicin (AC) {{#subobject:647f67|Regimen=1}}==
 
−
 
 
−
AC: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide
 
−
===Regimen variant #1, 4 cycles {{#subobject:b18877|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1997.15.7.2483 Fisher et al. 1997 (NSABP B-18)]
 
−
|1988-1993
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|Adjuvant [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]]
 
−
| style="background-color:#1a9850" |Superior resectability
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.2003.12.005 Bear et al. 2003 (NSABP B-27)]
 
−
|rowspan=2|1995-2000
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#AC-D|AC-D]]
 
−
| style="background-color:#d73027" |Inferior pCR rate
 
−
|-
 
−
|2. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29|AC]], then surgery, then [[#Docetaxel_monotherapy|T]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-007-9672-y Lee et al. 2007]
 
−
|2002-2005
 
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29|TX]]
+
|1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Nivolumab|CP & Nivolumab]]<br>1b. [[#Cisplatin_.26_Vinorelbine_.28CVb.29_.26_Nivolumab|CVb & Nivolumab]]<br>1c. [[#Cisplatin_.26_Docetaxel_.28DC.29_.26_Nivolumab|DC & Nivolumab]]
−
| style="background-color:#fc8d59" |Seems to have inferior pCR rate
+
| style="background-color:#d73027" |Inferior EFS
 
|-
 
|-
 
|}
 
|}
−
====Chemotherapy====
+
''Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. This study was conducted in the United States. The reason for the study was that an unanswered question at the time was whether adding an immune checkpoint inhibitor would improve outcomes.''
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
+
<div class="toccolours" style="background-color:#fdcdac">
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
====Subsequent treatment====
 
−
*NSABP B-18 & NSABP B-27: [[Surgery#Breast_cancer_surgery|Surgery]]
 
−
*Lee et al. 2007: [[Surgery#Breast_cancer_surgery|Surgery]], then [[#Capecitabine_.26_Docetaxel_.28TX.29_88|TX]] x 4
 
−
 
 
−
===Regimen variant #2, 6 cycles {{#subobject:d63ca0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdh175 Smith et al. 2004 (TOPIC)]
 
−
|1995-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ECisF_99|ECisF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of RFS/OS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdi276 Chua et al. 2005 (TOPIC 2)]
 
−
|1998-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_.26_Vinorelbine_.28VE.29_99|VE]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.06.156 Evans et al. 2005]
 
−
|1999-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Doxorubicin_.28AT.29_99|AD]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''NSABP B-18:''' Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB Jr, Fisher ER, Wickerham DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NV. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997 Jul;15(7):2483-93. [https://doi.org/10.1200/JCO.1997.15.7.2483 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9215816 PubMed]
 
−
## '''Update:''' Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. [https://doi.org/10.1200/JCO.1998.16.8.2672 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9704717 PubMed]
 
−
## '''Update:''' Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst. 2001;(30):96-102. [https://doi.org/10.1093/oxfordjournals.jncimonographs.a003469 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11773300 PubMed]
 
−
## '''Pooled update:''' Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. [https://doi.org/10.1200/JCO.2004.01.042 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15452182 PubMed]
 
−
## '''Pooled update:''' Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. [https://doi.org/10.1200/JCO.2007.15.0235 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18258986 PubMed]
 
−
# '''NSABP B-27:''' Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N; National Surgical Adjuvant Breast and Bowel Project. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003 Nov 15;21(22):4165-74. Epub 2003 Oct 14. [https://doi.org/10.1200/JCO.2003.12.005 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14559892 PubMed] NCT00002707
 
−
## '''Update:''' Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006 May 1;24(13):2019-27. Epub 2006 Apr 10. [https://doi.org/10.1200/JCO.2005.04.1665 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16606972 PubMed]
 
−
## '''Pooled update:''' Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. [https://doi.org/10.1200/JCO.2007.15.0235 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18258986 PubMed]
 
−
# '''TOPIC:''' Smith IE, A'Hern RP, Coombes GA, Howell A, Ebbs SR, Hickish TF, O'Brien ME, Mansi JL, Wilson CB, Robinson AC, Murray PA, Price CG, Perren TJ, Laing RW, Bliss JM; TOPIC Trial Group. A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neo-adjuvant treatment of early breast cancer: 5 year results of the TOPIC trial. Ann Oncol. 2004 May;15(5):751-8. [https://doi.org/10.1093/annonc/mdh175 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15111342 PubMed]
 
−
# Evans TR, Yellowlees A, Foster E, Earl H, Cameron DA, Hutcheon AW, Coleman RE, Perren T, Gallagher CJ, Quigley M, Crown J, Jones AL, Highley M, Leonard RC, Mansi JL; Anglo-Celtic Cooperative Oncology Group. Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an Anglo-Celtic Cooperative Oncology Group study. J Clin Oncol. 2005 May 1;23(13):2988-95. [https://doi.org/10.1200/JCO.2005.06.156 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15860854 PubMed]
 
−
## '''Update:''' Mansi JL, Yellowlees A, Lipscombe J, Earl HM, Cameron DA, Coleman RE, Perren T, Gallagher CJ, Quigley M, Crown J, Jones AL, Highley M, Leonard RC, Evans TR. Five-year outcome for women randomised in a phase III trial comparing doxorubicin and cyclophosphamide with doxorubicin and docetaxel as primary medical therapy in early breast cancer: an Anglo-Celtic Cooperative Oncology Group study. Breast Cancer Res Treat. 2010 Aug;122(3):787-94. Epub 2010 Jun 18. [https://doi.org/10.1007/s10549-010-0989-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20559708 PubMed]
 
−
# '''TOPIC 2:''' Chua S, Smith IE, A'Hern RP, Coombes GA, Hickish TF, Robinson AC, Laing RW, O'Brien ME, Ebbs SR, Hong A, Wardley A, Mughal T, Verrill M, Dubois D, Bliss JM; TOPIC Trial Group. Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response and tolerability in a randomised phase III trial (TOPIC 2). Ann Oncol. 2005 Sep;16(9):1435-41. Epub 2005 Jun 9. [https://doi.org/10.1093/annonc/mdi276 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15946977 PubMed]
 
−
# Lee KS, Ro J, Nam BH, Lee ES, Kwon Y, Kwon HS, Chung KW, Kang HS, Kim EA, Kim SW, Shin KH, Kim SK. A randomized phase-III trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage II/III breast cancer. Breast Cancer Res Treat. 2008 Jun;109(3):481-9. Epub 2007 Jul 26. [https://doi.org/10.1007/s10549-007-9672-y link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17653851 PubMed]
 
−
 
 
−
==Dose-dense Cyclophosphamide & Doxorubicin (ddAC) {{#subobject:dcfdd2|Regimen=1}}==
 
−
 
 
−
ddAC: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide
 
−
===Regimen {{#subobject:daff10|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.02.8621 Burstein et al. 2005]
 
−
|2003-2004
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2, given 24 hours after chemotherapy
 
−
*Burstein et al. 2005, for patients with Hb 10 to 12 g/dL:
 
−
**[[Darbepoetin alfa (Aranesp)]] 200 mcg SC once on day 1
 
−
***See Burstein et al. 2005 for additional dose adjustments
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*Optional [[#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29|dose-dense paclitaxel]], then [[Surgery#Breast_cancer_surgery|surgery]] or [[Surgery#Breast_cancer_surgery|surgery]], then [[#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|dose-dense paclitaxel]]; this was not a randomization
 
−
 
 
−
===References===
 
−
# Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. [https://doi.org/10.1200/jco.2005.02.8621 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16293865 PubMed]
 
−
 
 
−
==DI EC {{#subobject:31c3a1|Regimen=1}}==
 
−
 
 
−
DI EC: '''<u>D</u>'''ose-'''<u>I</u>'''ntense '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide
 
−
===Regimen {{#subobject:da1317|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdv216 Gonçalves et al. 2015 (UNICANCER PEGASE 07)]
 
−
|2001-2005
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
''This regimen required hematopoeitic stem cell support; see paper for details.''
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 150 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 4000 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[#Docetaxel_.26_Fluorouracil_99|Docetaxel & 5-FU]] versus [[Breast_cancer_-_null_regimens#Observation|no further treatment]]
 
−
 
 
−
===References===
 
−
# '''UNICANCER PEGASE 07:''' Gonçalves A, Pierga JY, Ferrero JM, Mouret-Reynier MA, Bachelot T, Delva R, Fabbro M, Lerebours F, Lotz JP, Linassier C, Dohollou N, Eymard JC, Leduc B, Lemonnier J, Martin AL, Boher JM, Viens P, Roché H. UNICANCER-PEGASE 07 study: a randomized phase III trial evaluating postoperative docetaxel-5FU regimen after neoadjuvant dose-intense chemotherapy for treatment of inflammatory breast cancer. Ann Oncol. 2015 Aug;26(8):1692-7. Epub 2015 May 5. [https://doi.org/10.1093/annonc/mdv216 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25943350 PubMed] NCT02324088
 
−
 
 
−
==Docetaxel & Epirubicin (DE) {{#subobject:d11f5f|Regimen=1}}==
 
−
 
 
−
DE: '''<u>D</u>'''ocetaxel & '''<u>E</u>'''pirubicin
 
−
<br>ED: '''<u>E</u>'''pirubicin & '''<u>D</u>'''ocetaxel
 
−
<br>ET: '''<u>E</u>'''pirubicin & '''<u>T</u>'''axotere (Docetaxel)
 
−
===Regimen variant #1, 3 cycles {{#subobject:c1953d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/full/10.1002/ijc.31217 Chen et al. 2017 (CBCRT01)]
 
−
|2011-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Epirubicin_.28DE.29_.26_Endostatin_77|DEE]]
 
−
| style="background-color:#d73027" |Inferior ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===Regimen variant #2, 6 cycles {{#subobject:c2184d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2006.09.1777 Steger et al. 2007 (ABCSG-14)]
 
−
|1999-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Docetaxel_.26_Epirubicin_.28DE.29|ED]] x 3
 
−
| style="background-color:#1a9850" |Superior pCR rate
 
−
|-
 
−
|[https://www.ejso.com/article/S0748-7983(09)00003-1 Han et al. 2009]
 
−
|2003-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Docetaxel_.26_Epirubicin_.28DE.29|ED]] x 4
 
−
| style="background-color:#91cf60" |Seems to have superior pCR rate
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdt508 Steger et al. 2013 (ABCSG-24)]
 
−
|2004-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#EDC|EDC]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''ABCSG-14:''' Steger GG, Galid A, Gnant M, Mlineritsch B, Lang A, Tausch C, Rudas M, Greil R, Wenzel C, Singer CF, Haid A, Pöstlberger S, Samonigg H, Luschin-Ebengreuth G, Kwasny W, Klug E, Kubista E, Menzel C, Jakesz R; ABCSG. Pathologic complete response with six compared with three cycles of neoadjuvant epirubicin plus docetaxel and granulocyte colony-stimulating factor in operable breast cancer: results of ABCSG-14. J Clin Oncol. 2007 May 20;25(15):2012-8. [https://doi.org/10.1200/JCO.2006.09.1777 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17513805 PubMed]
 
−
# Han S, Kim J, Lee J, Chang E, Gwak G, Cho H, Yang KH, Park S, Park K. Comparison of 6 cycles versus 4 cycles of neoadjuvant epirubicin plus docetaxel chemotherapy in stages II and III breast cancer. Eur J Surg Oncol. 2009 Jun;35(6):583-7. Epub 2009 Feb 5. [https://www.ejso.com/article/S0748-7983(09)00003-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19195817 PubMed]
 
−
# '''ABCSG-24:''' Steger GG, Greil R, Lang A, Rudas M, Fitzal F, Mlineritsch B, Hartmann BL, Bartsch R, Melbinger E, Hubalek M, Stoeger H, Dubsky P, Ressler S, Petzer AL, Singer CF, Muss C, Jakesz R, Gampenrieder SP, Zielinski CC, Fesl C, Gnant M; ABCSG. Epirubicin and docetaxel with or without capecitabine as neoadjuvant treatment for early breast cancer: final results of a randomized phase III study (ABCSG-24). Ann Oncol. 2014 Feb;25(2):366-71. Epub 2013 Dec 16. [https://doi.org/10.1093/annonc/mdt508 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24347519 PubMed] NCT00309556
 
−
# '''CBCRT01:''' Chen J, Yao Q, Huang M, Wang B, Zhang J, Wang T, Ming Y, Zhou X, Jia Q, Huan Y, Wang J, Wang L. A randomized Phase III trial of neoadjuvant recombinant human endostatin, docetaxel and epirubicin as first-line therapy for patients with breast cancer (CBCRT01). Int J Cancer. 2018 May 15;142(10):2130-2138. Epub 2017 Dec 23. [https://doi.org/full/10.1002/ijc.31217 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29238974 PubMed] NCT01479036
 
−
 
 
−
==EDC {{#subobject:g55f5f|Regimen=1}}==
 
−
 
 
−
EDC: '''<u>E</u>'''pirubicin, '''<u>D</u>'''ocetaxel, '''<u>C</u>'''apecitabine
 
−
===Regimen {{#subobject:d3824d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdt508 Steger et al. 2013 (ABCSG-24)]
 
−
|2004-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Docetaxel_.26_Epirubicin_.28DE.29|ED]]
 
−
| style="background-color:#91cf60" |Seems to have superior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''ABCSG-24:''' Steger GG, Greil R, Lang A, Rudas M, Fitzal F, Mlineritsch B, Hartmann BL, Bartsch R, Melbinger E, Hubalek M, Stoeger H, Dubsky P, Ressler S, Petzer AL, Singer CF, Muss C, Jakesz R, Gampenrieder SP, Zielinski CC, Fesl C, Gnant M; ABCSG. Epirubicin and docetaxel with or without capecitabine as neoadjuvant treatment for early breast cancer: final results of a randomized phase III study (ABCSG-24). Ann Oncol. 2014 Feb;25(2):366-71. Epub 2013 Dec 16. [https://doi.org/10.1093/annonc/mdt508 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24347519 PubMed] NCT00309556
 
−
 
 
−
==Epirubicin monotherapy {{#subobject:fdhtd3|Regimen=1}}==
 
−
 
 
−
E: '''<u>E</u>'''pirubicin
 
−
===Regimen {{#subobject:9abq2f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1677/erc.1.00945 Bottini et al. 2005]
 
−
|1997-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_.26_Tamoxifen_99|Epirubicin & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of clinical RR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
 
 
−
'''21-day cycle for 3 to 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
#Bottini A, Berruti A, Brizzi MP, Bersiga A, Generali D, Allevi G, Aguggini S, Bolsi G, Bonardi S, Tondelli B, Vana F, Tampellini M, Alquati P, Dogliotti L. Cytotoxic and antiproliferative activity of the single agent epirubicin versus epirubicin plus tamoxifen as primary chemotherapy in human breast cancer: a single-institution phase III trial. Endocr Relat Cancer. 2005 Jun;12(2):383-92. [https://doi.org/10.1677/erc.1.00945 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15947110/ PubMed]
 
−
 
 
−
==Epirubicin & Paclitaxel (EP) {{#subobject:38119e|Regimen=1}}==
 
−
 
 
−
EP: '''<u>E</u>'''pirubicin & '''<u>P</u>'''aclitaxel
 
−
<br>ET: '''<u>E</u>'''pirubicin & '''<u>T</u>'''axol (Paclitaxel)
 
−
===Regimen {{#subobject:040ce0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2008.20.3133 Untch et al. 2009 (TECHNO)]
 
−
|1998-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Dose-dense_E-P_88|ddE-P]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360722/ Frasci et al. 2006]
 
−
|1999-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#PET|PET]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior pCR rate
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*Frasci et al. 2006: [[Surgery#Breast_cancer_surgery|Surgery]], then [[#CMF|CMF]] x 4 or [[#FEC_2|FEC]] x 4, depending on number of involved lymph nodes
 
−
*TECHNO: [[Surgery#Breast_cancer_surgery|Surgery]], then [[#CMF|CMF]] x 3
 
−
 
 
−
===References===
 
−
# Frasci G, D'Aiuto G, Comella P, Thomas R, Botti G, Di Bonito M, De Rosa V, Iodice G, Rubulotta MR, Comella G; Southern Italy Cooperative Oncology Group. Weekly cisplatin, epirubicin, and paclitaxel with granulocyte colony-stimulating factor support vs triweekly epirubicin and paclitaxel in locally advanced breast cancer: final analysis of a SICOG phase III study. Br J Cancer. 2006 Oct 23;95(8):1005-12. [https://www.nature.com/articles/6603395 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360722/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17047649 PubMed]
 
−
# '''TECHNO:''' Untch M, Möbus V, Kuhn W, Muck BR, Thomssen C, Bauerfeind I, Harbeck N, Werner C, Lebeau A, Schneeweiss A, Kahlert S, von Koch F, Petry KU, Wallwiener D, Kreienberg R, Albert US, Lück HJ, Hinke A, Jänicke F, Konecny GE. Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol. 2009 Jun 20;27(18):2938-45. Epub 2009 Apr 13. [https://doi.org/10.1200/JCO.2008.20.3133 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19364964 PubMed]
 
−
 
 
−
==FAC {{#subobject:8d91b0|Regimen=1}}==
 
−
 
 
−
FAC: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
 
−
===Regimen variant #1, 500/50/500 {{#subobject:b845a59|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233286/ Arun et al. 2011 (MDACC 91-0156)]
 
−
|1992-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#DI_FAC_99|DI FAC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup>/day IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===Regimen variant #2, 600/50/600 {{#subobject:b99a59|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://journals.sagepub.com/doi/abs/10.1177/030089169708300511 Baldini et al. 1997]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#DES-CAF_99|DES-CAF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup>/day IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===Regimen variant #3, 1000/50/500 {{#subobject:1bb303|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1999.17.11.3412 Buzdar et al. 1999]
 
−
|1994-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_monotherapy_99|Paclitaxel]]; q3wk x 4
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 4
 
−
*[[Doxorubicin (Adriamycin)]] 16.7 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 50 mg/m<sup>2</sup>)
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[#FAC_2|FAC]] x 4
 
−
 
 
−
===Regimen variant #4, 2000/50/100 {{#subobject:1aa303|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ejcancer.com/article/0959-8049(94)90537-1/pdf Scholl et al. 1994 (S6)]
 
−
|1986-1990
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|Adjuvant [[#FAC_2|FAC]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1, 3, 5, 8
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 5
 
−
 
 
−
'''28-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''S6:''' Scholl SM, Fourquet A, Asselain B, Pierga JY, Vilcoq JR, Durand JC, Dorval T, Palangié T, Jouve M, Beuzeboc P, Garcio-Giralt E, Salmon RJ, de la Rochefordiere A, Campana F, Pouillart P. Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: preliminary results of a randomised trial: S6. Eur J Cancer. 1994;30A(5):645-52. [https://www.ejcancer.com/article/0959-8049(94)90537-1/pdf link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8080680 PubMed]
 
−
# Baldini E, Gardin G, Giannessi P, Brema F, Camorriano A, Carnino F, Naso C, Pastorino G, Pronzato P, Rosso R, Rubagotti A, Torretta G, Conte PF; North-West Oncology Group. A randomized trial of chemotherapy with or without estrogenic recruitment in locally advanced breast cancer. Tumori. 1997 Sep-Oct;83(5):829-33. [https://journals.sagepub.com/doi/abs/10.1177/030089169708300511 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9428917 PubMed]
 
−
# Buzdar AU, Singletary SE, Theriault RL, Booser DJ, Valero V, Ibrahim N, Smith TL, Asmar L, Frye D, Manuel N, Kau SW, McNeese M, Strom E, Hunt K, Ames F, Hortobagyi GN. Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer. J Clin Oncol. 1999 Nov;17(11):3412-7. [https://doi.org/10.1200/JCO.1999.17.11.3412 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10550135 PubMed]
 
−
# '''MDACC 91-0156:''' Arun BK, Dhinghra K, Valero V, Kau SW, Broglio K, Booser D, Guerra L, Yin G, Walters R, Sahin A, Ibrahim N, Buzdar AU, Frye D, Sneige N, Strom E, Ross M, Theriault RL, Vadhan-Raj S, Hortobagyi GN. Phase III randomized trial of dose intensive neoadjuvant chemotherapy with or without G-CSF in locally advanced breast cancer: long-term results. Oncologist. 2011;16(11):1527-34. Epub 2011 Oct 31. [http://theoncologist.alphamedpress.org/content/16/11/1527.long link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233286/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22042783 PubMed]
 
−
 
 
−
==FEC {{#subobject:ec48df|Regimen=1}}==
 
−
 
 
−
FEC: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide
 
−
 
 
−
===Regimen variant #1, 600/60/600 x 3 {{#subobject:792fef|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdg069 Baldini et al. 2003]
 
−
|1992-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Dose-dense_FEC_99|Dose-dense FEC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
''Note: This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[#FEC.2FCMF_88|CEF/CMF]] x 3
 
−
 
 
−
===Regimen variant #2, 600/60/600 x 4 {{#subobject:547837|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.22.4224 van der Hage et al. 2001 (EORTC 10902)]
 
−
|1991-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#FEC_2|FEC]]; adjuvant
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===Regimen variant #3, 1000/120/1050 x 6 {{#subobject:c3c026|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2003.05.135 Therasse et al. 2003 (EORTC 10921)]
 
−
|1993-1996
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Dose-dense_Cyclophosphamide_.26_Epirubicin_.28ddEC.29_99|ddEC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
===References===
 
−
# '''EORTC 10902:''' van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organisation for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001 Nov 15;19(22):4224-37. [https://doi.org/10.1200/JCO.2001.19.22.4224 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11709566 PubMed]
 
−
## '''Update:''' van Nes JG, Putter H, Julien JP, Tubiana-Hulin M, van de Vijver M, Bogaerts J, de Vos M, van de Velde CJ; Cooperating Investigators of the EORTC. Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902. Breast Cancer Res Treat. 2009 May;115(1):101-13. Epub 2008 May 18. [https://doi.org/10.1007/s10549-008-0050-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18484198 PubMed]
 
−
# Baldini E, Gardin G, Giannessi PG, Evangelista G, Roncella M, Prochilo T, Collecchi P, Rosso R, Lionetto R, Bruzzi P, Mosca F, Conte PF. Accelerated versus standard cyclophosphamide, epirubicin and 5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil: a randomized phase III trial in locally advanced breast cancer. Ann Oncol. 2003 Feb;14(2):227-32. [https://doi.org/10.1093/annonc/mdg069 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12562649 PubMed]
 
−
# '''EORTC 10921:''' Therasse P, Mauriac L, Welnicka-Jaskiewicz M, Bruning P, Cufer T, Bonnefoi H, Tomiak E, Pritchard KI, Hamilton A, Piccart MJ; [[Study_Groups#EORTC|EORTC]]. Final results of a randomized phase III trial comparing cyclophosphamide, epirubicin, and fluorouracil with a dose-intensified epirubicin and cyclophosphamide + filgrastim as neoadjuvant treatment in locally advanced breast cancer: an EORTC-NCIC-SAKK multicenter study. J Clin Oncol. 2003 Mar 1;21(5):843-50. [https://doi.org/10.1200/JCO.2003.05.135 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12610183 PubMed]
 
−
 
 
−
==iddEPC {{#subobject:28hga2|Regimen=1}}==
 
−
 
 
−
iddEPC: '''<u>i</u>'''ntense '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>E</u>'''pirubicin, '''<u>P</u>'''aclitaxel, '''<u>C</u>'''yclophosphamide
 
−
===Protocol {{#subobject:65az1d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.ejca.2018.10.015 Schneeweiss et al. 2018 (GeparOcto)]
 
−
|2014-NR in abstract
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#NPLD_.26_Paclitaxel_77|NPLD & Paclitaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
''Note: G-CSF details are from the adjuvant trial; see paper for exact details.''
 
−
====Chemotherapy, part 1====
 
−
*[[Epirubicin (Ellence)]] 150 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2 or 4
 
−
 
 
−
'''14-day cycle for 3 cycles, then:'''
 
−
====Chemotherapy, part 2====
 
−
*[[Paclitaxel (Taxol)]] 225 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2 or 4
 
−
 
 
−
'''14-day cycle for 3 cycles, then:'''
 
−
====Chemotherapy, part 3====
 
−
*[[Cyclophosphamide (Cytoxan)]] 2000 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2 or 4
 
−
 
 
−
'''14-day cycle for 3 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# '''GeparOcto:''' Schneeweiss A, Möbus V, Tesch H, Hanusch C, Denkert C, Lübbe K, Huober J, Klare P, Kümmel S, Untch M, Kast K, Jackisch C, Thomalla J, Ingold-Heppner B, Blohmer JU, Rezai M, Frank M, Engels K, Rhiem K, Fasching PA, Nekljudova V, von Minckwitz G, Loibl S. Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto-GBG 84): A randomised phase III trial. Eur J Cancer. 2019 Jan;106:181-192. Epub 2018 Dec 5. [https://doi.org/10.1016/j.ejca.2018.10.015 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30528802/ PubMed] NCT02125344
 
−
## '''Update:''' Schneeweiss A, Michel LL, Möbus V, Tesch H, Klare P, Hahnen E, Denkert C, Kast K, Pohl-Rescigno E, Hanusch C, Link T, Untch M, Jackisch C, Blohmer JU, Fasching PA, Solbach C, Schmutzler RK, Huober J, Rhiem K, Nekljudova V, Lübbe K, Loibl S; GBG and AGO-B. Survival analysis of the randomised phase III GeparOcto trial comparing neoadjuvant chemotherapy of intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for patients with high-risk early breast cancer. Eur J Cancer. 2022 Jan;160:100-111. Epub 2021 Nov 17. [https://doi.org/10.1016/j.ejca.2021.10.011 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34801353/ PubMed]
 
−
 
 
−
==Paclitaxel monotherapy, dose-dense (q2wk) {{#subobject:fa1c6b|Regimen=1}}==
 
−
 
 
−
ddT: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>T</u>'''axol (Paclitaxel)
 
−
===Regimen {{#subobject:b5be66|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.02.8621 Burstein et al. 2005]
 
−
|2003-2004
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*Burstein et al. 2005: [[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29|ddAC]] x 4
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*Burstein et al. 2005: [[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*Burstein et al. 2005: [[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. [https://doi.org/10.1200/jco.2005.02.8621 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16293865 PubMed]
 
−
 
 
−
==PET {{#subobject:47221e|Regimen=1}}==
 
−
 
 
−
PET: '''<u>P</u>'''latinol (Cisplatin), '''<u>E</u>'''pirubicin, '''<u>T</u>'''axol (Paclitaxel)
 
−
===Regimen {{#subobject:181ce0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360722/ Frasci et al. 2006]
 
−
|1999-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Epirubicin_.26_Paclitaxel_.28EP.29|EP]]
 
−
| style="background-color:#91cf60" |Seems to have superior pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
*[[Paclitaxel (Taxol)]] 120 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*Frasci et al. 2006: [[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
===References===
 
−
# Frasci G, D'Aiuto G, Comella P, Thomas R, Botti G, Di Bonito M, De Rosa V, Iodice G, Rubulotta MR, Comella G; Southern Italy Cooperative Oncology Group. Weekly cisplatin, epirubicin, and paclitaxel with granulocyte colony-stimulating factor support vs triweekly epirubicin and paclitaxel in locally advanced breast cancer: final analysis of a SICOG phase III study. Br J Cancer. 2006 Oct 23;95(8):1005-12. [https://www.nature.com/articles/6603395 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360722/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17047649 PubMed]
 
−
 
 
−
==TAC (Docetaxel) {{#subobject:413b30|Regimen=1}}==
 
−
 
 
−
TAC: '''<u>T</u>'''axotere (Docetaxel), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
 
−
<br>ATC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''yclophosphamide
 
−
===Regimen {{#subobject:8dbe27|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/100/8/542/931241 von Minckwitz et al. 2008 (GeparTrio)]
 
−
|2002-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#TAC_.28Docetaxel.29|TAC]] x 2, then [[Stub#Capecitabine_.26_Vinorelbine|NX]] x 4
 
−
| style="background-color:#eeee01" |Non-inferior sonographic response
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(13)00487-5 Vriens et al. 2013 (INTENS)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#AC-D|AC-D]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
===References===
 
−
# '''GeparTrio:''' von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C, Loibl S, Mehta K, Kaufmann M; [[Study_Groups#GBG|GBG]]. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst. 2008 Apr 16;100(8):542-51. Epub 2008 Apr 8. [https://academic.oup.com/jnci/article/100/8/542/931241 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18398097 PubMed] NCT00544765
 
−
##'''Update:''' von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C, Loibl S, Mehta K, Kaufmann M; German Breast Group. Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst. 2008 Apr 16;100(8):552-62. Epub 2008 Apr 8. [https://doi.org/10.1093/jnci/djn089 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18398094/ PubMed]
 
−
# '''INTENS:''' Vriens BE, Aarts MJ, de Vries B, van Gastel SM, Wals J, Smilde TJ, van Warmerdam LJ, de Boer M, van Spronsen DJ, Borm GF, Tjan-Heijnen VC; BOOG. Doxorubicin/cyclophosphamide with concurrent versus sequential docetaxel as neoadjuvant treatment in patients with breast cancer. Eur J Cancer. 2013 Oct;49(15):3102-10. Epub 2013 Jul 10. [https://www.ejcancer.com/article/S0959-8049(13)00487-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23850450 PubMed] NCT00314977
 
−
## '''Update:''' Vriens BEPJ, Vriens IJH, Aarts MJB, van Gastel SM, van den Berkmortel FWPJ, Smilde TJ, van Warmerdam LJC, van Spronsen DJ, Peer PGM, de Boer M, Tjan-Heijnen VCG; BOOG. Improved survival for sequentially as opposed to concurrently delivered neoadjuvant chemotherapy in non-metastatic breast cancer. Breast Cancer Res Treat. 2017 Oct;165(3):593-600. Epub 2017 Jul 3. [https://doi.org/10.1007/s10549-017-4364-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602024/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28674765 PubMed]
 
−
 
 
−
=Neoadjuvant response criteria=
 
−
 
 
−
==Clinical response rate (cRR)==
 
−
 
 
−
''Although fairly dated, some trials such as [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107749/ ACOSOG Z1031] make use of the WHO criteria for response to neoadjuvant therapy. Included here primarily for historical purposes.''
 
−
===References===
 
−
# Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207-14. [https://doi.org/10.1002/1097-0142(19810101)47:1%3C207::AID-CNCR2820470134%3E3.0.CO;2-6 link to original article]  [https://pubmed.ncbi.nlm.nih.gov/7459811 PubMed]
 
−
 
 
−
==Miller-Payne scoring system==
 
−
 
 
−
*Grade 1: No change or some changes to individual malignant cells, but no reduction in overall cellularity
 
−
*Grade 2: Minor loss of tumor cells (up to 30%), but overall cellularity still high
 
−
*Grade 3: An estimated 30 to 90% reduction in the number of tumor cells
 
−
*Grade 4: Marked disappearance of tumor cells such that only small clusters or widely dispersed individual cells remain (loss of greater than 90% of tumor cells)
 
−
*Grade 5: No invasive cancer cells identifiable in sections from the site of the tumor (carcinoma ''in situ'' may be present)
 
−
===References===
 
−
# Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003 Oct;12(5):320-7. [http://www.thebreastonline.com/article/S0960-9776(03)00106-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14659147 PubMed]
 
−
 
 
−
==Residual cancer burden (RCB)==
 
−
 
 
−
*The RCB is calculated as follows: RCB = 1.4 (''f<sub>inv</sub>*d<sub>prim</sub>'')<sup>0.17</sup> + [4(1 - 0.75<sup>''LN''</sup>)''d<sub>met</sub>'']<sup>0.17</sup>
 
−
**where ''d<sub>prim</sub>'' is derived from the bidimensional diameters of the primary tumor bed in the resected specimen, ''f<sub>inv</sub>'' is the proportion of the primary tumor bed that contains invasive carcinoma, ''LN'' is the number of axillary lymph nodes containing metastatic carcinoma, and ''d<sub>met</sub>'' is the diameter of the largest metastasis in an axillary lymph node.
 
−
**The cut-off points are 1.36 and 3.28.
 
−
===References===
 
−
# Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007 Oct 1;25(28):4414-22. Epub 2007 Sep 4. [https://doi.org/10.1200/JCO.2007.10.6823 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17785706 PubMed]
 
−
 
 
−
==Residual disease in breast and nodes (RDBN)==
 
−
 
 
−
*Level 1: pCR in breast and nodes with or without ''in situ'' carcinoma
 
−
*Levels 2 to 4: Residual disease, calculated as 0.2 (residual breast tumor size in cm) + index of involved nodes (0 for no positive nodes, 1 for 1 to 4 positive nodes, 2 for 5 to 7 positive nodes, and 3 for 8 positive nodes) + the Scarff–Bloom–Richardson grade (1, 2, or 3). The cut-off points are 3 and 4.3.
 
−
===References===
 
−
# Chollet P, Abrial C, Durando X, Thivat E, Tacca O, Mouret-Reynier MA, Leheurteur M, Kwiatkowski F, Dauplat J, Penault-Llorca F. A new prognostic classification after primary chemotherapy for breast cancer: residual disease in breast and nodes (RDBN). Cancer J. 2008 Mar-Apr;14(2):128-32. [https://insights.ovid.com/pubmed?pmid=18391619 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18391619 PubMed]
 
−
 
 
−
==Sataloff's classification==
 
−
 
 
−
*Breast:
 
−
**T-A: Total or nearly total therapeutic effect
 
−
**T-B: Greater than 50% therapeutic effect
 
−
**T-C: Less than 50% therapeutic effect
 
−
**T-D: No therapeutic effect
 
−
*Lymph node:
 
−
**N-A: Therapeutic effect but no metastasis
 
−
**N-B: No metastasis, no therapeutic effect
 
−
**N-C: Therapeutic effect but metastasis
 
−
**N-D: Metastasis, no therapeutic effect
 
−
===References===
 
−
# Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995 Mar;180(3):297-306. [https://pubmed.ncbi.nlm.nih.gov/7874340 PubMed]
 
−
 
 
−
==Tumor response ratio==
 
−
 
 
−
Calculated as follows: Residual breast disease observed upon pathologic examination divided by the size of the tumor on the pre-neoadjuvant therapy image.
 
−
*TRR = 0: pathologic complete response (pCR)
 
−
*TRR greater than 0 up to 0.4: strong partial response
 
−
*TRR greater than 0.4 up to 1.0: weak partial response (WPR)
 
−
*TRR greater than 1.0: tumor growth
 
−
===References===
 
−
# Miller M, Ottesen RA, Niland JC, Kruper L, Chen SL, Vito C. Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2014 Oct;21(10):3317-23. Epub 2014 Jul 25. [https://link.springer.com/article/10.1245/s10434-014-3922-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25059788 PubMed]
 
−
 
 
−
==ypTNM staging==
 
−
 
 
−
This system is proprietary to the AJCC. Please [https://cancerstaging.org/Pages/default.aspx visit their site] or consult the AJCC Manual for further details.
 
−
 
 
−
=Adjuvant chemotherapy, sequential protocols=
 
−
==A-CMF {{#subobject:68h17c|Regimen=1}}==
 
−
 
 
−
A-CMF: '''<u>A</u>'''driamycin (Doxorubicin) followed by '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
−
===Protocol variant #1, IV classical CMF {{#subobject:80hg17|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ Fernando et al. 2019 (SECRAB)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CMF_.26_RT_88|CMF & RT]]<br>2. [[#E-CMF_.26_RT_88|E-CMF & RT]]<br>3. [[#A-CMF_.26_RT_88|A-CMF & RT]]<br>4. [[#MMM_.26_RT_88|MMM & RT]]
 
−
| style="background-color:#d73027" |Inferior LRFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy, A portion====
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles, followed by:'''
 
−
 
 
−
====Chemotherapy, CMF portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 4 cycles'''
 
−
 
 
−
===Protocol variant #2, PO classical CMF {{#subobject:8077qq|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ Fernando et al. 2019 (SECRAB)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CMF_.26_RT_88|CMF & RT]]<br>2. [[#E-CMF_.26_RT_88|E-CMF & RT]]<br>3. [[#A-CMF_.26_RT_88|A-CMF & RT]]<br>4. [[#MMM_.26_RT_88|MMM & RT]]
 
−
| style="background-color:#d73027" |Inferior LRFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy, A portion====
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles, followed by:'''
 
−
 
 
−
====Chemotherapy, CMF portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 4 cycles'''
 
−
 
 
−
===References===
 
−
# '''SECRAB:''' Fernando IN, Bowden SJ, Herring K, Brookes CL, Ahmed I, Marshall A, Grieve R, Churn M, Spooner D, Latief TN, Agrawal RK, Brunt AM, Stevens A, Goodman A, Canney P, Bishop J, Ritchie D, Dunn J, Poole CJ, Rea DW; SECRAB Investigators. Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial. Radiother Oncol. 2020 Jan;142:52-61. Epub 2019 Nov 27. [https://doi.org/10.1016/j.radonc.2019.10.014 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31785830/ PubMed] NCT00003893
 
−
 
 
−
==AC-CMF {{#subobject:68ug7c|Regimen=1}}==
 
−
 
 
−
AC-CMF: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide followed by '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
−
===Regimen {{#subobject:807v2z|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.03.0783 Colleoni et al. 2006 (IBCSG 13-93)]
 
−
|1993-1999
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.03.5196 Basser et al. 2006 (IBCSG 15-95)]
 
−
|1995-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Dose-intense_Epirubicin_.26_Cyclophosphamide_.28(DI-EC).29_88|DI-EC]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS<sup>1</sup>
 
−
|-
 
−
|rowspan=2|[https://academic.oup.com/jnci/article/100/2/121/1130035 Francis et al. 2008 (BIG 02-98)]
 
−
|rowspan=2|1998-2001
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#A-CMF|A-CMF]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[#A-D-CMF_88|A-D-CMF]]<br>3. [[#AD-CMF_88|AD-CMF]]
 
−
| style="background-color:#fee08b" |Might have inferior DFS<sup>2</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for IBCSG 15-95 is based on the 2009 update.''<br>
 
−
''<sup>2</sup>Reported efficacy for BIG 02-98 is based on the 2015 update.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 4: 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, CMF portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 7: 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 5 to 7: 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 5 to 7: 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''21-day cycle for 4 cycles, then 28-day cycle for 3 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 y versus [[Breast_cancer_-_null_regimens#Observation|no further treatment]]
 
−
 
 
−
===References===
 
−
#'''IBCSG 15-95:''' Basser RL, O'Neill A, Martinelli G, Green MD, Peccatori F, Cinieri S, Coates AS, Gelber RD, Aebi S, Castiglione-Gertsch M, Viale G, Price KN, Goldhirsch A; International Breast Cancer Study Group. Multicycle dose-intensive chemotherapy for women with high-risk primary breast cancer: results of International Breast Cancer Study Group Trial 15-95. J Clin Oncol. 2006 Jan 20;24(3):370-8. [https://doi.org/10.1200/jco.2005.03.5196 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16421418/ PubMed] NCT00002784
 
−
##'''Update:''' Colleoni M, Sun Z, Martinelli G, Basser RL, Coates AS, Gelber RD, Green MD, Peccatori F, Cinieri S, Aebi S, Viale G, Price KN, Goldhirsch A; International Breast Cancer Study Group. The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up. Ann Oncol. 2009 Aug;20(8):1344-51. Epub 2009 May 25. [https://doi.org/10.1093/annonc/mdp024 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2720817/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19468030/ PubMed]
 
−
# '''IBCSG 13-93:''' Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiglione-Gertsch M, Price KN, Coates AS, Gelber RD; International Breast Cancer Study Group. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol. 2006 Mar 20;24(9):1332-41. Epub 2006 Feb 27. [https://doi.org/10.1200/JCO.2005.03.0783 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16505417 PubMed]
 
−
# '''BIG 02-98:''' Francis P, Crown J, Di Leo A, Buyse M, Balil A, Andersson M, Nordenskjöld B, Lang I, Jakesz R, Vorobiof D, Gutiérrez J, van Hazel G, Dolci S, Jamin S, Bendahmane B, Gelber RD, Goldhirsch A, Castiglione-Gertsch M, Piccart-Gebhart M; BIG. Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial. J Natl Cancer Inst. 2008 Jan 16;100(2):121-33. Epub 2008 Jan 8. Erratum in: J Natl Cancer Inst. 2008 Nov 19;100(22):1655. [https://academic.oup.com/jnci/article/100/2/121/1130035 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18182617 PubMed] NCT00174655
 
−
## '''Update:''' Oakman C, Francis PA, Crown J, Quinaux E, Buyse M, De Azambuja E, Margeli Vila M, Andersson M, Nordenskjöld B, Jakesz R, Thürlimann B, Gutiérrez J, Harvey V, Punzalan L, Dell'orto P, Larsimont D, Steinberg I, Gelber RD, Piccart-Gebhart M, Viale G, Di Leo A. Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer--8-year results of the Breast International Group 02-98 phase III trial. Ann Oncol. 2013 May;24(5):1203-11. Epub 2013 Jan 4. [https://doi.org/10.1093/annonc/mds627 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23293111 PubMed]
 
−
## '''Update:''' Sonnenblick A, Francis PA, Azim HA Jr, de Azambuja E, Nordenskjöld B, Gutiérez J, Quinaux E, Mastropasqua MG, Ameye L, Anderson M, Lluch A, Gnant M, Goldhirsch A, Di Leo A, Barnadas A, Cortes-Funes H, Piccart M, Crown J. Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer. Eur J Cancer. 2015 Aug;51(12):1481-9. Epub 2015 Jun 11. [https://www.ejcancer.com/article/S0959-8049(15)00285-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26074397 PubMed]
 
−
 
 
−
==AC-D {{#subobject:68hg67|Regimen=1}}==
 
−
 
 
−
AC-D: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide followed by '''<u>D</u>'''ocetaxel
 
−
===Protocol variant #1, q3wk docetaxel 75 mg/m<sup>2</sup> {{#subobject:80hgca|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan="2"|[https://doi.org/10.1002/cncr.30421 Watanabe et al. 2017 (NSAS BC-02)]
 
−
| rowspan = 2|2001-2006
 
−
| rowspan = 2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#AC-T_2|AC-T]]<br>2. [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]] x 8
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>(HR 0.75, 95% CI 0.57-0.98)
 
−
|-
 
−
|3. [[#Docetaxel_monotherapy|Docetaxel]] x 8
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles, followed by:'''
 
−
 
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===Protocol variant #2, q3wk docetaxel 100 mg/m<sup>2</sup> {{#subobject:807gua|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ Sparano et al. 2008 (ECOG E1199)]
 
−
| rowspan="2" |1999-2002
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#AC-T_2|AC-T]]; q3wk paclitaxel
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|2. [[#AC-T_2|AC-T]]; weekly paclitaxel<br> 3. [[#AC-D_2|AC-D]]; weekly docetaxel
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935316/ Swain et al. 2010 (NSABP B-30)]
 
−
|rowspan=2|1999-2004
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Docetaxel_.26_Doxorubicin_.28AT.29_88|AT]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|2. [[#TAC_.28Docetaxel.29_2|TAC]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2010.28.5437 Eiermann et al. 2011 (BCIRG-005)]
 
−
|2000-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#TAC_.28Docetaxel.29_2|TAC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles, followed by:'''
 
−
 
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===Protocol variant #2, weekly docetaxel {{#subobject:199d79|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ Sparano et al. 2008 (ECOG E1199)]
 
−
| rowspan="2" |1999-2002
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#AC_T_2|AC-T]]; q3wk paclitaxel
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|2. [[#AC_T_2|AC-T]]; weekly paclitaxel<br> 3. [[#AC_D_2|AC-D]]; q3wk docetaxel
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles, followed by:'''
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''7-day cycle for 12 cycles'''
 
−
 
 
−
===References===
 
−
<!-- Presented in part at the San Antonio Breast Cancer Symposium, San Antonio, Texas, December 8–11, 2007, and the American Society of Clinical Oncology meeting, Chicago, June 1–4, 2005. -->
 
−
# '''ECOG E1199:''' Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. [https://doi.org/10.1056/NEJMoa0707056 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18420499 PubMed] NCT00004125
 
−
## '''Update:''' Sparano JA, Zhao F, Martino S, Ligibel JA, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer. J Clin Oncol. 2015 Jul 20;33(21):2353-60. Epub 2015 Jun 15. [https://doi.org/10.1200/jco.2015.60.9271 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500829/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26077235 PubMed]
 
−
# '''NSABP B-30:''' Swain SM, Jeong JH, Geyer CE Jr, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff J, Vogel VG, Erban JK, Rastogi P, Livingston RB, Perez EA, Mamounas EP, Land SR, Ganz PA, Wolmark N. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med. 2010 Jun 3;362(22):2053-65. [https://doi.org/10.1056/NEJMoa0909638 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935316/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20519679 PubMed] NCT00003782
 
−
<!-- Presented in part at the 28th Annual San Antonio Breast Cancer Symposia, December 8-11, 2005, San Antonio, TX, and at the 31st Annual San Antonio Breast Cancer Symposia, December 10-14, 2008, San Antonio, TX. -->
 
−
# '''BCIRG-005:''' Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martín M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press M, Sauter G, Lindsay MA, Riva A, Buyse M, Drevot P, Taupin H, Mackey JR. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011 Oct 10;29(29):3877-84. Epub 2011 Sep 12. [https://doi.org/10.1200/jco.2010.28.5437 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21911726 PubMed] NCT00312208
 
−
## '''Update:''' Mackey JR, Pieńkowski T, Crown J, Sadeghi S, Martín M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press MF, Sauter G, Lindsay M, Houé V, Buyse M, Drevot P, Hitier S, Bensfia S, Eiermann W; Translational Research In Oncology (TRIO)/ Breast Cancer International Research Group (BCIRG)-005 investigators. Long-term outcomes after adjuvant treatment of sequential versus combination docetaxel with doxorubicin and cyclophosphamide in node-positive breast cancer: BCIRG-005 randomized trial. Ann Oncol. 2016 Jun;27(6):1041-7. Epub 2016 Mar 2. [https://doi.org/10.1093/annonc/mdw098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26940688 PubMed]
 
−
# '''NSAS BC-02:''' Watanabe T, Kuranami M, Inoue K, Masuda N, Aogi K, Ohno S, Iwata H, Mukai H, Uemura Y, Ohashi Y. Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study. Cancer. 2017 Mar 1;123(5):759-768. Epub 2017 Jan 12. [https://doi.org/10.1002/cncr.30421 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28081304 PubMed]
 
−
 
 
−
==AC-T {{#subobject:633n67|Regimen=1}}==
 
−
 
 
−
AC-T: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide followed by '''<u>T</u>'''axol (Paclitaxel)
 
−
===Regimen variant #1, weekly paclitaxel {{#subobject:6516e6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ Sparano et al. 2008 (ECOG E1199)]
 
−
| rowspan="2" |1999-2002
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#AC-T_2|AC-T]]; q3wk paclitaxel
 
−
| style="background-color:#1a9850" |Superior OS<br>OS60: 89.7% vs 86.5%<br>(HR 0.76, 98.3% CI 0.58-0.98)
 
−
|-
 
−
|2. [[#AC-D_2|AC-D]]; q3wk docetaxel<br>3. [[#AC-D_2|AC-D]]; weekly docetaxel
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7007289/ Fehrenbacher et al. 2019 (NSABP B-47)]
 
−
|2011-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#AC-TH_99|AC-TH]]<br>2. [[#Dose-dense_AC-TH_99|ddAC-TH]]<br>3. [[#TCH_99|TCH]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS
 
−
|-
 
−
|}
 
−
''Note: this regimen has been studied in many trials; these may be referenced under the individual components AC or T. Over time we will migrate these studies here.''
 
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
−
*NSABP B-47: HER2 IHC of 1+ or 2+ with FISH ratio less than 2 or HER2 gene copy number less than 4
+
*CheckMate 816: No sensitizing EGFR or ALK mutations
−
 
+
</div>
−
====Preceding treatment====
+
<div class="toccolours" style="background-color:#b3e2cd">
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 4: 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 5 to 8: 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #2, q3wk paclitaxel 175 mg/m<sup>2</sup> {{#subobject:80c6e6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.09.081 Citron et al. 2003 (CALGB 9741)]
 
−
|1997-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
−
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
−
|-
 
−
| rowspan="3" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ Sparano et al. 2008 (ECOG E1199)]
 
−
| rowspan="3" |1999-2002
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#AC-T_2|AC-T]]; weekly paclitaxel
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|2. [[#AC-D_2|AC-D]]; q3wk docetaxel
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
−
|-
 
−
|3. [[#AC-D_2|AC-D]]; weekly docetaxel
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2009.24.1000 Loesch et al. 2010]
 
−
|2000-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#Loesch_et_al._2010|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#Loesch_et_al._2010|See link]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799234/ Burnell et al. 2009 (NCIC-CTG MA.21)]
 
−
|2000-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#NCIC_CTG_MA.21|See link]]
 
−
| style="background-color:#d73027" |[[Complex_multipart_regimens#NCIC_CTG_MA.21|See link]]
 
−
|-
 
−
|rowspan="2"|[https://doi.org/10.1002/cncr.30421 Watanabe et al. 2017 (NSAS BC-02)]
 
−
| rowspan = 2|2001-2006
 
−
| rowspan = 2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#AC-D_2|AC-D]]<br>2. [[#Docetaxel_monotherapy|Docetaxel]] x 8
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|3. [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]] x 8
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS
 
−
|-
 
−
|}
 
−
''Note: this regimen has been studied in many trials; these may be referenced under the individual components AC or T. Over time we will migrate these studies here.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 4: 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 5 to 8: 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #3, q3wk paclitaxel 225 mg/m<sup>2</sup> {{#subobject:80c6uv|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.10.517 Mamounas et al. 2005 (NSABP B-28)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy, AC portion====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 4: 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 5 to 8: 225 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===References===
 
−
# '''CALGB 9741:''' Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. [https://doi.org/10.1200/jco.2003.09.081 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12668651 PubMed] NCT00003088
 
−
# '''NSABP B-28:''' Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. [https://doi.org/10.1200/jco.2005.10.517 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15897552 PubMed]
 
−
<!-- Presented in part at the San Antonio Breast Cancer Symposium, San Antonio, Texas, December 8–11, 2007, and the American Society of Clinical Oncology meeting, Chicago, June 1–4, 2005. -->
 
−
# '''ECOG E1199:''' Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. [https://doi.org/10.1056/NEJMoa0707056 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18420499 PubMed] NCT00004125
 
−
## '''Update:''' Sparano JA, Zhao F, Martino S, Ligibel JA, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer. J Clin Oncol. 2015 Jul 20;33(21):2353-60. Epub 2015 Jun 15. [https://doi.org/10.1200/jco.2015.60.9271 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500829/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26077235 PubMed]
 
−
# '''NCIC-CTG MA.21:''' Burnell M, Levine MN, Chapman JA, Bramwell V, Gelmon K, Walley B, Vandenberg T, Chalchal H, Albain KS, Perez EA, Rugo H, Pritchard K, O'Brien P, Shepherd LE. Cyclophosphamide, epirubicin, and fluorouracil versus dose-dense epirubicin and cyclophosphamide followed by paclitaxel versus doxorubicin and cyclophosphamide followed by paclitaxel in node-positive or high-risk node-negative breast cancer. J Clin Oncol. 2010 Jan 1;28(1):77-82. Epub 2009 Nov 9. [https://doi.org/10.1200/JCO.2009.22.1077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799234/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19901117 PubMed] NCT00014222
 
−
# Loesch D, Greco FA, Senzer NN, Burris HA, Hainsworth JD, Jones S, Vukelja SJ, Sandbach J, Holmes F, Sedlacek S, Pippen J, Lindquist D, McIntyre K, Blum JL, Modiano MR, Boehm KA, Zhan F, Asmar L, Robert N. Phase III multicenter trial of doxorubicin plus cyclophosphamide followed by paclitaxel compared with doxorubicin plus paclitaxel followed by weekly paclitaxel as adjuvant therapy for women with high-risk breast cancer. J Clin Oncol. 2010 Jun 20;28(18):2958-65. Epub 2010 May 17. [https://doi.org/10.1200/JCO.2009.24.1000 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20479419 PubMed]
 
−
# '''NSAS BC-02:''' Watanabe T, Kuranami M, Inoue K, Masuda N, Aogi K, Ohno S, Iwata H, Mukai H, Uemura Y, Ohashi Y. Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study. Cancer. 2017 Mar 1;123(5):759-768. Epub 2017 Jan 12. [https://doi.org/10.1002/cncr.30421 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28081304 PubMed]
 
−
# '''NSABP B-47:''' Fehrenbacher L, Cecchini RS, Geyer CE Jr, Rastogi P, Costantino JP, Atkins JN, Crown JP, Polikoff J, Boileau JF, Provencher L, Stokoe C, Moore TD, Robidoux A, Flynn PJ, Borges VF, Albain KS, Swain SM, Paik S, Mamounas EP, Wolmark N. NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+ or 2. J Clin Oncol. 2020 Feb 10;38(5):444-453. Epub 2019 Dec 10. [https://doi.org/10.1200/jco.19.01455 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7007289/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31821109/ PubMed] NCT01275677
 
−
 
 
−
==Dose-dense AC-T {{#subobject:b594g6|Regimen=1}}==
 
−
 
 
−
ddAC-T: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide followed by '''<u>T</u>'''axol (Paclitaxel)
 
−
===Protocol variant #1, q2wk paclitaxel {{#subobject:cyrqd0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.09.081 Citron et al. 2003 (CALGB 9741)]
 
−
|1997-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
−
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, ddAC portion====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg (rounded to either 300 or 480 mcg) SC once per day on days 3 to 10
 
−
**Note: Citron et al. 2003 says the schedule was "filgrastim days 3 to 10 of each cycle (a total of seven doses)," so it is unclear whether 7 or 8 doses was actually used).
 
−
 
 
−
'''14-day cycle for 4 cycles, followed by:'''
 
−
 
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Diphenhydramine (Benadryl)]] 12.5 to 50 mg IV once on day 1; 30 to 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
*One of the following H2 blockers:
 
−
**[[Ranitidine (Zantac)]] 50 mg IV once on day 1; 30 to 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
**[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 to 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
**[[Famotidine (Pepcid)]] 20 mg IV once on day 1; 30 to 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
*One of the following dexamethasone choices:
 
−
**[[Dexamethasone (Decadron)]] 10 mg IV once on day 1, within 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
**[[Dexamethasone (Decadron)]] 10 mg PO once on day 1, at least 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
**[[Dexamethasone (Decadron)]] 20 mg PO twice on day 1; 6 hours and 12 hours prior to [[Paclitaxel (Taxol)]]
 
−
*Recommended growth factor support with one of the following:
 
−
**[[Filgrastim (Neupogen)]] 5 mcg/kg (rounded to 300 mcg or 480 mcg, whichever is closer) SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
 
−
**[[Sargramostim (Leukine)]] 250 to 500 mcg/m<sup>2</sup> SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
 
−
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once, given 24 to 36 hours after chemotherapy
 
−
***GIM2: a mid-protocol amendment suggested giving the pegilgrastim at least 72 h after chemotherapy
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
 
 
−
===Protocol variant #2, weekly paclitaxel {{#subobject:chnz10|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7007289/ Fehrenbacher et al. 2019 (NSABP B-47)]
 
−
|2011-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#AC-TH_99|AC-TH]]<br>2. [[#Dose-dense_AC-TH_99|ddAC-TH]]<br>3. [[#TCH_99|TCH]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS
 
−
|-
 
−
|}
 
−
''Note: Fehrenbacher et al. 2019 does not explicitly describe the use of filgrastim, but it is typically used for this regimen.''
 
−
====Biomarker eligibility criteria====
 
−
*NSABP B-47: HER2 IHC of 1+ or 2+ with FISH ratio less than 2 or HER2 gene copy number less than 4
 
−
 
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, ddAC portion====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg (rounded to either 300 or 480 mcg) SC once per day on days 3 to 10
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
 
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''7-day cycle for 12 cycles'''
 
−
 
 
−
===References===
 
−
# '''CALGB 9741:''' Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. [https://doi.org/10.1200/jco.2003.09.081 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12668651 PubMed] NCT00003088
 
−
# '''NSABP B-47:''' Fehrenbacher L, Cecchini RS, Geyer CE Jr, Rastogi P, Costantino JP, Atkins JN, Crown JP, Polikoff J, Boileau JF, Provencher L, Stokoe C, Moore TD, Robidoux A, Flynn PJ, Borges VF, Albain KS, Swain SM, Paik S, Mamounas EP, Wolmark N. NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+ or 2. J Clin Oncol. 2020 Feb 10;38(5):444-453. Epub 2019 Dec 10. [https://doi.org/10.1200/jco.19.01455 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7007289/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31821109/ PubMed] NCT01275677
 
−
 
 
−
==D-EC {{#subobject:fd4ug8|Regimen=1}}==
 
−
 
 
−
D-EC: '''<u>D</u>'''ocetaxel followed by '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide
 
−
===Protocol {{#subobject:1aad71|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-009-0468-0 Polyzos et al. 2009]
 
−
|1995-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#FEC_2|FEC]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles, followed by:'''
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 700 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===References===
 
−
# Polyzos A, Malamos N, Boukovinas I, Adamou A, Ziras N, Kalbakis K, Kakolyris S, Syrigos K, Papakotoulas P, Kouroussis C, Karvounis N, Vamvakas L, Christophyllakis C, Athanasiadis A, Varthalitis I, Georgoulias V, Mavroudis D; Hellenic Oncology Research Group. FEC versus sequential docetaxel followed by epirubicin/cyclophosphamide as adjuvant chemotherapy in women with axillary node-positive early breast cancer: a randomized study of the Hellenic Oncology Research Group (HORG). Breast Cancer Res Treat. 2010 Jan;119(1):95-104. Epub 2009 Jul 28. [https://doi.org/10.1007/s10549-009-0468-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19636702 PubMed]
 
−
 
 
−
==D-FEC {{#subobject:fdhg38|Regimen=1}}==
 
−
 
 
−
D-FEC: '''<u>D</u>'''ocetaxel followed by '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide
 
−
<br>T-CEF: '''<u>T</u>'''axotere (Docetaxel) followed by <u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>F</u>'''luorouracil'''
 
−
===Protocol {{#subobject:1zzk71|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(09)70307-9 Joensuu et al. 2009 (FinXX)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TX-CEX|TX-CEX]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] 80 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
====Chemotherapy, FEC portion====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
 
 
−
===References===
 
−
# '''FinXX:''' Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Asola R, Kokko R, Ahlgren J, Auvinen P, Hemminki A, Paija O, Helle L, Nuortio L, Villman K, Nilsson G, Lahtela SL, Lehtiö K, Pajunen M, Poikonen P, Nyandoto P, Kataja V, Bono P, Leinonen M, Lindman H; FinXX Study Investigators. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial. Lancet Oncol. 2009 Dec;10(12):1145-51. Epub 2009 Nov 10. [https://doi.org/10.1016/s1470-2045(09)70307-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19906561 PubMed] NCT00114816
 
−
## '''Update:''' Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Paija O, Helle L, Villman K, Nyandoto P, Nilsson G, Pajunen M, Asola R, Poikonen P, Leinonen M, Kataja V, Bono P, Lindman H. Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial. J Clin Oncol. 2012 Jan 1;30(1):11-8. Epub 2011 Nov 21. [https://doi.org/10.1200/JCO.2011.35.4639 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22105826 PubMed]
 
−
## '''Update:''' Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola A, Tanner M, Ahlgren J, Auvinen P, Lahdenperä O, Villman K, Nyandoto P, Nilsson G, Poikonen-Saksela P, Kataja V, Bono P, Junnila J, Lindman H. Adjuvant Capecitabine for Early Breast Cancer: 15-Year Overall Survival Results From a Randomized Trial. J Clin Oncol. 2022 Apr 1;40(10):1051-1058. Epub 2022 Jan 12. [https://doi.org/10.1200/jco.21.02054 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966968/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35020465/ PubMed]
 
−
 
 
−
==E-CMF {{#subobject:fd4rf3|Regimen=1}}==
 
−
 
 
−
E-CMF: '''<u>E</u>'''pirubicin followed by '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
−
===Regimen variant #1, 100/750/50/600 {{#subobject:agbd2f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa052084 Poole et al. 2006 (BR9601)]
 
−
|1996-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#CMF|CMF]] x 6
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS60: 84% vs 78%<br>(HR 0.76, 95% CI 0.65-0.89)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ Fernando et al. 2019 (SECRAB)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CMF_.26_RT_88|CMF & RT]]<br>2. [[#E-CMF_.26_RT_88|E-CMF & RT]]<br>3. [[#A-CMF_.26_RT_88|A-CMF & RT]]<br>4. [[#MMM_.26_RT_88|MMM & RT]]
 
−
| style="background-color:#d73027" |Inferior LRFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.01371 Delaloge et al. 2020 (MINDACT)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_99|TX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2012 update.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, E portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, CMF portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 5 to 8: 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #2, 100/1200/80/1200 {{#subobject:5u5d2f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa052084 Poole et al. 2006 (NEAT)]
 
−
|1996-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#CMF|CMF]] x 6
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS60: 84% vs 78%<br>(HR 0.76, 95% CI 0.65-0.89)
 
−
|-
 
−
|[https://doi.org/10.1159/000315735 Boccardo et al. 2010]
 
−
|1997-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#T-EV_99|T-EV]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1007/s10549-010-1257-5 Amadori et al. 2010 (IRST-IBIS-03)]
 
−
|rowspan=2|1997-2004
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CMF|CMF]] x 6
 
−
|style="background-color:#d3d3d3"|Not reported
 
−
|-
 
−
|[[#CMF-E_99|CMF-E]]
 
−
|style="background-color:#ffffbf"|Did not meet endpoint of OS60
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ Fernando et al. 2019 (SECRAB)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CMF_.26_RT_88|CMF & RT]]<br>2. [[#E-CMF_.26_RT_88|E-CMF & RT]]<br>3. [[#A-CMF_.26_RT_88|A-CMF & RT]]<br>4. [[#MMM_.26_RT_88|MMM & RT]]
 
−
| style="background-color:#d73027" |Inferior LRFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687939/ Ellis et al. 2009 (TACT)]
 
−
|2001-2003
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#FEC-D|FEC-D]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489700/ Cameron et al. 2017 (TACT2)]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#TACT2|See link]]
 
−
| style="background-color:#eeee01" |[[Complex_multipart_regimens#TACT2|See link]]
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2012 update.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, E portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, CMF portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 5 to 8: 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''21-day cycle for 4 cycles, then 28-day cycle for 4 cycles'''
 
−
 
 
−
===Regimen variant #3, 100/1400/80/1200 ("classic CMF") {{#subobject:91td2f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa052084 Poole et al. 2006 (NEAT)]
 
−
|1996-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#CMF|CMF]] x 6
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS60: 84% vs 78%<br>(HR 0.76, 95% CI 0.65-0.89)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ Fernando et al. 2019 (SECRAB)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CMF_.26_RT_88|CMF & RT]]<br>2. [[#E-CMF_.26_RT_88|E-CMF & RT]]<br>3. [[#A-CMF_.26_RT_88|A-CMF & RT]]<br>4. [[#MMM_.26_RT_88|MMM & RT]]
 
−
| style="background-color:#d73027" |Inferior LRFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489700/ Cameron et al. 2017 (TACT2)]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#TACT2|See link]]
 
−
| style="background-color:#eeee01" |[[Complex_multipart_regimens#TACT2|See link]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.01371 Delaloge et al. 2020 (MINDACT)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_99|TX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2012 update.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, E portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, CMF portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 5 to 8: 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 5 to 8: 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''21-day cycle for 4 cycles, then 28-day cycle for 4 cycles'''
 
−
===References===
 
−
<!-- no pre-pub disclosed -->
 
−
# '''NEAT:''' Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. [https://doi.org/10.1056/nejmoa052084 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17079759 PubMed] NCT00003577
 
−
## '''Update:''' Earl HM, Hiller L, Dunn JA, Vallier AL, Bowden SJ, Jordan SD, Blows F, Munro A, Bathers S, Grieve R, Spooner DA, Agrawal R, Fernando I, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, McAdam K, Foster L, Leonard RC, Twelves CJ, Cameron D, Bartlett JM, Pharoah P, Provenzano E, Caldas C, Poole CJ; NEAT Investigators and the SCTBG. Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials. Br J Cancer. 2012 Oct 9;107(8):1257-67. Epub 2012 Sep 11. [https://doi.org/10.1038/bjc.2012.370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494422/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23047592 PubMed]
 
−
<!-- no pre-pub disclosed -->
 
−
# '''BR9601:''' Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. [https://doi.org/10.1056/nejmoa052084 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17079759 PubMed] NCT00003012
 
−
## '''Update:''' Earl HM, Hiller L, Dunn JA, Vallier AL, Bowden SJ, Jordan SD, Blows F, Munro A, Bathers S, Grieve R, Spooner DA, Agrawal R, Fernando I, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, McAdam K, Foster L, Leonard RC, Twelves CJ, Cameron D, Bartlett JM, Pharoah P, Provenzano E, Caldas C, Poole CJ; NEAT Investigators and the SCTBG. Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials. Br J Cancer. 2012 Oct 9;107(8):1257-67. Epub 2012 Sep 11. [https://doi.org/10.1038/bjc.2012.370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494422/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23047592 PubMed]
 
−
# '''TACT:''' Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. [https://doi.org/10.1016/S0140-6736(09)60740-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687939/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19447249 PubMed] ISRCTN79718493
 
−
# Boccardo F, Amadori D, Guglielmini P, Sismondi P, Farris A, Agostara B, Gambi A, Catalano G, Faedi M, Rubagotti A. Epirubicin followed by cyclophosphamide, methotrexate and 5-fluorouracil versus paclitaxel followed by epirubicin and vinorelbine in patients with high-risk operable breast cancer. Oncology. 2010;78(3-4):274-81. Epub 2010 Jun 8. [https://doi.org/10.1159/000315735 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20530973 PubMed]
 
−
# '''IRST-IBIS-03:''' Amadori D, Silvestrini R, De Lena M, Boccardo F, Rocca A, Scarpi E, Schittulli F, Brandi M, Maltoni R, Serra P, Ponzone R, Biglia N, Gianni L, Tienghi A, Valerio MR, Bonginelli P, Amaducci L, Faedi M, Baldini E, Paradiso A. Randomized phase III trial of adjuvant epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) versus CMF followed by epirubicin in patients with node-negative or 1-3 node-positive rapidly proliferating breast cancer. Breast Cancer Res Treat. 2011 Feb;125(3):775-84. Epub 2010 Dec 4. [https://doi.org/10.1007/s10549-010-1257-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21132360 PubMed] NCT01031030
 
−
# '''TACT2:''' Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, Agrawal R, Banerji J, Bertelli G, Bloomfield D, Brunt AM, Earl H, Ellis P, Gaunt C, Gillman A, Hearfield N, Laing R, Murray N, Couper N, Stein RC, Verrill M, Wardley A, Barrett-Lee P, Bliss JM; TACT2 Investigators. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2017 Jul;18(7):929-945. Epub 2017 Jun 7. [https://doi.org/10.1016/S1470-2045(17)30404-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489700/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28600210 PubMed] NCT00301925
 
−
# '''SECRAB:''' Fernando IN, Bowden SJ, Herring K, Brookes CL, Ahmed I, Marshall A, Grieve R, Churn M, Spooner D, Latief TN, Agrawal RK, Brunt AM, Stevens A, Goodman A, Canney P, Bishop J, Ritchie D, Dunn J, Poole CJ, Rea DW; SECRAB Investigators. Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial. Radiother Oncol. 2020 Jan;142:52-61. Epub 2019 Nov 27. [https://doi.org/10.1016/j.radonc.2019.10.014 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31785830/ PubMed] NCT00003893
 
−
# '''MINDACT:''' Delaloge S, Piccart M, Rutgers E, Litière S, van 't Veer LJ, van den Berkmortel F, Brain E, Dudek-Peric A, Gil-Gil M, Gomez P, Hilbers FS, Khalil Z, Knox S, Kuemmel S, Kunz G, Lesur A, Pierga JY, Ravdin P, Rubio IT, Saghatchian M, Smilde TJ, Thompson AM, Viale G, Zoppoli G, Vuylsteke P, Tryfonidis K, Poncet C, Bogaerts J, Cardoso F; MINDACT investigators and the TRANSBIG Consortium. Standard Anthracycline Based Versus Docetaxel-Capecitabine in Early High Clinical and/or Genomic Risk Breast Cancer in the EORTC 10041/BIG 3-04 MINDACT Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1186-1197. Epub 2020 Feb 21. [https://doi.org/10.1200/jco.19.01371 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/32083990 PubMed] NCT00433589
 
−
 
 
−
==E-D {{#subobject:8knrf3|Regimen=1}}==
 
−
 
 
−
E-D: '''<u>E</u>'''pirubicin followed by '''<u>D</u>'''ocetaxel
 
−
===Protocol variant #1 {{#subobject:bf8gub|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.32.7254 Coombes et al. 2011 (DEVA)]
 
−
|1997-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Epirubicin_monotherapy_2|Epirubicin]]
 
−
| style="background-color:#1a9850" |Superior OS<br>OS60: 88.9% vs 81.8%<br>(HR 0.66, 95% CI 0.46-0.94)
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, E portion====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 3 cycles'''
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
 
 
−
===Protocol variant #2 {{#subobject:bf8gub|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584474/ Mavroudis et al. 2017 (HORG CT/01.04)]
 
−
|2001-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Epirubicin_.26_Docetaxel_99|Epirubicin & Docetaxel]]
 
−
| style="background-color:#d9ef8b" |Might have superior DFS<br>DFS60: 92.6% vs 88.2%<br>(HR 0.63, 95% CI 0.39-1.01)
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, E portion====
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV over 5 to 15 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===References===
 
−
<!-- Presented at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL. -->
 
−
# '''DEVA:''' Coombes RC, Bliss JM, Espie M, Erdkamp F, Wals J, Tres A, Marty M, Coleman RE, Tubiana-Mathieu N, den Boer MO, Wardley A, Kilburn LS, Cooper D, Thomas MW, Reise JA, Wilkinson K, Hupperets P. Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with  node-positive breast cancer. J Clin Oncol. 2011 Aug 20;29(24):3247-54. Epub 2011 Jul 18. [https://doi.org/10.1200/JCO.2010.32.7254 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21768453 PubMed] ISRCTN89772270
 
−
# '''HORG CT/01.04:''' Mavroudis D, Saloustros E, Boukovinas I, Papakotoulas P, Kakolyris S, Ziras N, Christophylakis C, Kentepozidis N, Fountzilas G, Rigas G, Varthalitis I, Kalbakis K, Agelaki S, Hatzidaki D, Georgoulias V; Hellenic Oncology Research Group. Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group. Br J Cancer. 2017 Jul 11;117(2):164-170. Epub 2017 Jun 22. [https://doi.org/10.1038/bjc.2017.158 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584474/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28641315 PubMed] NCT00424606
 
−
 
 
−
==EC-CMF {{#subobject:xk9g7c|Regimen=1}}==
 
−
 
 
−
EC-CMF: '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide followed by '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
−
===Regimen {{#subobject:80ghx1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.03.0783 Colleoni et al. 2006 (IBCSG 13-93)]
 
−
|1993-1999
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.03.5196 Basser et al. 2006 (IBCSG 15-95)]
 
−
|1995-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Dose-intense_Epirubicin_.26_Cyclophosphamide_.28(DI-EC).29_88|DI-EC]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2009 update.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 4: 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, CMF portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 7: 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 5 to 7: 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 5 to 7: 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''21-day cycle for 4 cycles, then 28-day cycle for 3 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 y versus [[Breast_cancer_-_null_regimens#Observation|no further treatment]]
 
−
 
 
−
===References===
 
−
#'''IBCSG 15-95:''' Basser RL, O'Neill A, Martinelli G, Green MD, Peccatori F, Cinieri S, Coates AS, Gelber RD, Aebi S, Castiglione-Gertsch M, Viale G, Price KN, Goldhirsch A; International Breast Cancer Study Group. Multicycle dose-intensive chemotherapy for women with high-risk primary breast cancer: results of International Breast Cancer Study Group Trial 15-95. J Clin Oncol. 2006 Jan 20;24(3):370-8. [https://doi.org/10.1200/jco.2005.03.5196 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16421418/ PubMed] NCT00002784
 
−
##'''Update:''' Colleoni M, Sun Z, Martinelli G, Basser RL, Coates AS, Gelber RD, Green MD, Peccatori F, Cinieri S, Aebi S, Viale G, Price KN, Goldhirsch A; International Breast Cancer Study Group. The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up. Ann Oncol. 2009 Aug;20(8):1344-51. Epub 2009 May 25. [https://doi.org/10.1093/annonc/mdp024 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2720817/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19468030/ PubMed]
 
−
# '''IBCSG 13-93:''' Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiglione-Gertsch M, Price KN, Coates AS, Gelber RD; International Breast Cancer Study Group. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol. 2006 Mar 20;24(9):1332-41. Epub 2006 Feb 27. [https://doi.org/10.1200/JCO.2005.03.0783 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16505417 PubMed]
 
−
 
 
−
==EC-D {{#subobject:8d8duq|Regimen=1}}==
 
−
 
 
−
EC-D: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide followed by '''<u>D</u>'''ocetaxel
 
−
<br>EC-T: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide followed by '''<u>T</u>'''axotere (Docetaxel)
 
−
===Protocol variant #1, 3+3 cycles {{#subobject:8d62d4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.72.3494 Ejlertsen et al. 2017 (DBCG 07-READ)]
 
−
|2008-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Docetaxel_.28TC.29|TC]] x 6
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Biomarker eligibility criteria====
 
−
*TOP2A normal as determined by FISH
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
 
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
 
 
−
===Protocol variant #2, 4+4 cycles {{#subobject:22hy7f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2015.61.9510 Martín et al. 2015 (GEICAM 2003-10)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ET-X_99|ET-X]] x 4+4
 
−
| style="background-color:#91cf60" |Seems to have superior IDFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
===References===
 
−
# '''WSG-AGO EC-Doc:''' Nitz U, Gluz O, Huober J, Kreipe HH, Kates RE, Hartmann A, Erber R, Moustafa Z, Scholz M, Lisboa B, Mohrmann S, Möbus V, Augustin D, Hoffmann G, Weiss E, Böhmer S, Kreienberg R, Du Bois A, Sattler D, Thomssen C, Kiechle M, Jänicke F, Wallwiener D, Harbeck N, Kuhn W. Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression. Ann Oncol. 2014 Aug;25(8):1551-7. Epub 2014 May 14. Erratum in: Ann Oncol. 2017 Nov 1;28(11):2899. [https://doi.org/10.1093/annonc/mdu186 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24827128 PubMed] NCT02115204
 
−
# '''GEICAM 2003-10:''' Martín M, Ruiz Simón A, Ruiz Borrego M, Ribelles N, Rodríguez-Lescure A, Muñoz-Mateu M, González S, Margelí Vila M, Barnadas A, Ramos M, Del Barco Berron S, Jara C, Calvo L, Martínez-Jáñez N, Mendiola Fernández C, Rodríguez CA, Martínez de Dueñas E, Andrés R, Plazaola A, de la Haba-Rodríguez J, López-Vega JM, Adrover E, Ballesteros AI, Santaballa A, Sánchez-Rovira P, Baena-Cañada JM, Casas M, del Carmen Cámara M, Carrasco EM, Lluch A. Epirubicin plus cyclophosphamide followed by docetaxel versus epirubicin plus docetaxel followed by capecitabine as adjuvant therapy for node-positive early breast cancer: results from the GEICAM/2003-10 study. J Clin Oncol. 2015 Nov 10;33(32):3788-95. Epub 2015 Sep 28. [https://doi.org/10.1200/JCO.2015.61.9510 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26416999 PubMed] NCT00129935
 
−
# '''DBCG 07-READ:''' Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Højris I, Ewertz M, Balslev E, Danø H, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol. 2017 Aug 10;35(23):2639-2646. Epub 2017 Jun 29. [https://doi.org/10.1200/JCO.2017.72.3494 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28661759 PubMed] NCT00689156
 
−
 
 
−
==EC-T {{#subobject:8d8dy1|Regimen=1}}==
 
−
 
 
−
EC-T: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide followed by '''<u>T</u>'''axol (Paclitaxel)
 
−
<br>EC-P: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide followed by '''<u>P</u>'''aclitaxel
 
−
===Regimen variant #1, 75/600 {{#subobject:8hgaz4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8486325/ Yu et al. 2021 (SPECTRUM<sub>brca</sub>)]
 
−
|2011-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#EP-T_88|EP-T]]
 
−
| style="background-color:#fee08b" |Might have inferior DFS60
 
−
|-
 
−
|}
 
−
''Note: this trial should not be confused with the one by the same name in head & neck cancer.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 4: 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 5 to 8: 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #2, 90/600 {{#subobject:8hhyg4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(17)30319-4 Earl et al. 2017 (tAnGo)]
 
−
|2001-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#EC-TG_.28Paclitaxel.29_99|EC-TG]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/s0140-6736(14)62048-1 Del Mastro et al. 2015 (GIM2)]
 
−
|rowspan=2|2003-2006
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#ddEC-ddT_.28Paclitaxel.29|ddEC-ddT]]<br>2. [[#ddFEC-ddT_.28Paclitaxel.29_99|ddFEC-ddT]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|3. [[#FEC-P|FEC-P]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, EC portion====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 4: 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 5 to 8: 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===References===
 
−
# '''GIM2:''' Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; GIM. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. Epub 2015 Mar 2. [https://doi.org/10.1016/s0140-6736(14)62048-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25740286 PubMed] NCT00433420
 
−
# '''tAnGo:''' Earl HM, Hiller L, Howard HC, Dunn JA, Young J, Bowden SJ, McDermaid M, Waterhouse AK, Wilson G, Agrawal R, O'Reilly S, Bowman A, Ritchie DM, Goodman A, Hickish T, McAdam K, Cameron D, Dodwell D, Rea DW, Caldas C, Provenzano E, Abraham JE, Canney P, Crown JP, Kennedy MJ, Coleman R, Leonard RC, Carmichael JA, Wardley AM, Poole CJ; tAnGo trial collaborators. Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):755-769. Epub 2017 May 4. [https://doi.org/10.1016/s1470-2045(17)30319-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28479233 PubMed] NCT00039546
 
−
#'''SPECTRUM<sub>brca</sub>:''' Yu KD, Ge JY, Liu XY, Mo M, He M, Shao ZM; SPECTRUM Investigators. Cyclophosphamide-Free Adjuvant Chemotherapy for Ovarian Protection in Young Women With Breast Cancer: A Randomized Phase 3 Trial. J Natl Cancer Inst. 2021 Oct 1;113(10):1352-1359. [https://doi.org/10.1093/jnci/djab065 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8486325/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33822134/ PubMed] NCT01026116
 
−
 
 
−
==FEC-D {{#subobject:fduea3|Regimen=1}}==
 
−
 
 
−
FEC-D: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide followed by '''<u>D</u>'''ocetaxel
 
−
===Regimen variant #1, 3 x 3 {{#subobject:9hu942|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.07.3916 Roché et al. 2006 (FNCLCC PACS 01)]
 
−
|1997-2000
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#FEC_2|FEC]] x 6
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS96: 83.2% vs 78%<br>(aHR 0.75, 95% CI 0.62-0.92)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7583247/ de Gregorio et al. 2020 (SUCCESS-A)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC-DG_99|FEC-DG]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1007/s12032-013-0457-3 Sakr et al. 2013]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#FEC_2|FEC]]; FEC 100 x 6
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(18)30939-0 Campone et al. 2018 (UCBG 2-08)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC-Ixabepilone_99|FEC-Ixabepilone]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/fullarticle/2579866 Foukakis et al. 2016 (PANTHER)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Dose-dense tailored chemotherapy
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.01371 Delaloge et al. 2020 (MINDACT)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_99|TX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for FNCLCC PACS 01 is based on the 2012 update.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, FEC portion====
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 1 to 3: 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 3: 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 3: 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycles 4 to 6: 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #2, 4 x 4 {{#subobject:9hu942|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687939/ Ellis et al. 2009 (TACT)]
 
−
|2001-2003
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|1. [[#E-CMF|E-CMF]]<br>2. [[#FEC_2|FEC]] x 8
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, FEC portion====
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 4: 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycles 5 to 8: 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
===References===
 
−
<!-- Presented in oral format at the 27th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-11, 2004. -->
 
−
# '''FNCLCC PACS 01:''' Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, Symann M, Kerbrat P, Soulié P, Eichler F, Viens P, Monnier A, Vindevoghel A, Campone M, Goudier MJ, Bonneterre J, Ferrero JM, Martin AL, Genève J, Asselain B. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006 Dec 20;24(36):5664-71. Epub 2006 Nov 20. [https://doi.org/10.1200/jco.2006.07.3916 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17116941 PubMed]
 
−
## '''Update:''' Coudert B, Asselain B, Campone M, Spielmann M, Machiels JP, Pénault-Llorca F, Serin D, Lévy C, Romieu G, Canon JL, Orfeuvre H, Piot G, Petit T, Jerusalem G, Audhuy B, Veyret C, Beauduin M, Eymard JC, Martin AL, Roché H; UNICANCER Breast Group. Extended benefit from sequential administration of docetaxel after standard fluorouracil, epirubicin, and cyclophosphamide regimen for node-positive breast cancer: the 8-year follow-up results of the UNICANCER-PACS01 trial. Oncologist. 2012;17(7):900-9. Epub 2012 May 18. [http://theoncologist.alphamedpress.org/content/17/7/900.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399644/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22610153 PubMed]
 
−
# '''TACT:''' Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. [https://doi.org/10.1016/S0140-6736(09)60740-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687939/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19447249 PubMed] ISRCTN79718493
 
−
# Sakr H, Hamed RH, Anter AH, Yossef T. Sequential docetaxel as adjuvant chemotherapy for node-positive or/and T3 or T4 breast cancer: clinical outcome (Mansoura University). Med Oncol. 2013 Mar;30(1):457. Epub 2013 Jan 16. [https://doi.org/10.1007/s12032-013-0457-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23322524 PubMed]
 
−
# '''PANTHER:''' Foukakis T, von Minckwitz G, Bengtsson NO, Brandberg Y, Wallberg B, Fornander T, Mlineritsch B, Schmatloch S, Singer CF, Steger G, Egle D, Karlsson E, Carlsson L, Loibl S, Untch M, Hellström M, Johansson H, Anderson H, Malmström P, Gnant M, Greil R, Möbus V, Bergh J; Swedish Breast Cancer Group; German Breast Group; Austrian Breast & Colorectal Cancer Study Group. Effect of tailored dose-dense chemotherapy vs standard 3-weekly adjuvant chemotherapy on recurrence-free survival among women with high-risk early breast cancer: a randomized clinical trial. JAMA. 2016 Nov 8;316(18):1888-1896. [https://jamanetwork.com/journals/jama/fullarticle/2579866 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27825007 PubMed] NCT00798070
 
−
# '''UCBG 2-08:''' Campone M, Lacroix-Triki M, Roca L, Spielmann M, Wildiers H, Cottu P, Kerbrat P, Levy C, Desmoulins I, Bachelot T, Winston T, Eymard JC, Uwer L, Duhoux FP, Verhoeven D, Jaubert D, Coeffic D, Orfeuvre H, Canon JL, Asselain B, Martin AL, Lemonnier J, Roché H. UCBG 2-08: 5-year efficacy results from the UNICANCER-PACS08 randomised phase III trial of adjuvant treatment with FEC100 and then either docetaxel or ixabepilone in patients with early-stage, poor prognosis breast cancer. Eur J Cancer. 2018 Nov;103:184-194. Epub 2018 Sep 26. [https://www.ejcancer.com/article/S0959-8049(18)30939-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30267987 PubMed] NCT00630032
 
−
# '''MINDACT:''' Delaloge S, Piccart M, Rutgers E, Litière S, van 't Veer LJ, van den Berkmortel F, Brain E, Dudek-Peric A, Gil-Gil M, Gomez P, Hilbers FS, Khalil Z, Knox S, Kuemmel S, Kunz G, Lesur A, Pierga JY, Ravdin P, Rubio IT, Saghatchian M, Smilde TJ, Thompson AM, Viale G, Zoppoli G, Vuylsteke P, Tryfonidis K, Poncet C, Bogaerts J, Cardoso F; MINDACT investigators and the TRANSBIG Consortium. Standard Anthracycline Based Versus Docetaxel-Capecitabine in Early High Clinical and/or Genomic Risk Breast Cancer in the EORTC 10041/BIG 3-04 MINDACT Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1186-1197. Epub 2020 Feb 21. [https://doi.org/10.1200/jco.19.01371 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/32083990 PubMed] NCT00433589
 
−
# '''SUCCESS-A:''' de Gregorio A, Häberle L, Fasching PA, Müller V, Schrader I, Lorenz R, Forstbauer H, Friedl TWP, Bauer E, de Gregorio N, Deniz M, Fink V, Bekes I, Andergassen U, Schneeweiss A, Tesch H, Mahner S, Brucker SY, Blohmer JU, Fehm TN, Heinrich G, Lato K, Beckmann MW, Rack B, Janni W. Gemcitabine as adjuvant chemotherapy in patients with high-risk early breast cancer-results from the randomized phase III SUCCESS-A trial. Breast Cancer Res. 2020 Oct 23;22(1):111. [https://doi.org/10.1186/s13058-020-01348-w link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7583247/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33097092/ PubMed] NCT02181101
 
−
 
 
−
==Dose-dense FEC-D {{#subobject:45dbc1|Regimen=1}}==
 
−
 
 
−
ddFEC-D: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide followed by '''<u>D</u>'''ocetaxel
 
−
===Regimen {{#subobject:05e37f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdw274 Mavroudis et al. 2016 (HORG CT/07.17)]
 
−
|2007-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Docetaxel_.28TC.29|TC]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS36
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, ddFEC portion====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|Filgrastim]] or [[Pegfilgrastim (Neulasta)]] support (drug/dose/schedule not specified)
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
====Chemotherapy, D portion====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|Filgrastim]] or [[:Category:Granulocyte_colony-stimulating_factors|Pegfilgrastim]] support (drug/dose/schedule not specified)
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
 
 
−
===References===
 
−
# '''HORG CT/07.17:''' Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; HORG. Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2016 Oct;27(10):1873-8. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw274 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27502729 PubMed] NCT01985724
 
−
 
 
−
==FEC-P {{#subobject:fd16bz|Regimen=1}}==
 
−
 
 
−
FEC-P: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide followed by '''<u>P</u>'''aclitaxel
 
−
<br>FEC-T: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide followed by '''<u>T</u>'''axol (Paclitaxel)
 
−
===Protocol {{#subobject:9hu942|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://jnci.oxfordjournals.org/content/100/11/805.long Martín et al. 2008 (GEICAM 9906)]
 
−
|1999-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#FEC_2|FEC]] x 6
 
−
| style="background-color:#1a9850" |Superior DFS<br>DFS60: 78.5% vs 72.1%<br>(HR 0.77, 95% CI 0.62-0.95)
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, FEC portion====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles, followed by:'''
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''7-day cycle for 8 cycles'''
 
−
 
 
−
===References===
 
−
# '''GEICAM 9906:''' Martín M, Rodríguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Munárriz B, Rodríguez CA, Crespo C, de Alava E, López García-Asenjo JA, Guitián MD, Almenar S, González-Palacios JF, Vera F, Palacios J, Ramos M, Gracia Marco JM, Lluch A, Alvarez I, Seguí MA, Mayordomo JI, Antón A, Baena JM, Plazaola A, Modolell A, Pelegrí A, Mel JR, Aranda E, Adrover E, Alvarez JV, García Puche JL, Sánchez-Rovira P, Gonzalez S, López-Vega JM; GEICAM. Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Natl Cancer Inst. 2008 Jun 4;100(11):805-14. Epub 2008 May 27. [http://jnci.oxfordjournals.org/content/100/11/805.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18505968 PubMed] NCT00129922
 
−
# '''GIM2:''' Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; GIM. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. Epub 2015 Mar 2. [https://doi.org/10.1016/s0140-6736(14)62048-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25740286 PubMed] NCT00433420
 
−
 
 
−
==T-FEC {{#subobject:ug8h8g|Regimen=1}}==
 
−
 
 
−
T-FEC: '''<u>T</u>'''axol (Paclitaxel), followed by '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide
 
−
===Regimen {{#subobject:7y2gny|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2011.36.2079 Kelly et al. 2012 (MDACC ID01-580)]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TX-FEC_.28Docetaxel.29|TX-FEC]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of RFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, T portion====
 
−
*[[Paclitaxel (Taxol)]] as follows:
 
−
**Cycles 1 to 4: 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
====Chemotherapy, FEC portion====
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 5 to 8: 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 5 to 8: 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 5 to 8: 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===References===
 
−
<!-- Presented at the 44th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 30-June 3, 2008. -->
 
−
# '''MDACC ID01-580:''' Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU. Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol. 2012 Mar 20;30(9):930-5. Epub 2012 Feb 13. [https://doi.org/10.1200/JCO.2011.36.2079 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22331946 PubMed] NCT00050167
 
−
 
 
−
==TX-CEX {{#subobject:fdhg38|Regimen=1}}==
 
−
 
 
−
TX-CEX: '''<u>T</u>'''axotere (Docetaxel) & '''<u>X</u>'''eloda (Capecitabine) followed by '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>X</u>'''eloda (Capecitabine)
 
−
===Protocol {{#subobject:1zzk71|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(09)70307-9 Joensuu et al. 2009 (FinXX)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#D-FEC_2|D-FEC]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>OS180: 77.6% vs 73.3%<br>(HR 0.81, 95% CI 0.66-0.99)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, TX portion====
 
−
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
*[[Capecitabine (Xeloda)]] 900 mg/m<sup>2</sup> PO twice per day on days 1 to 15
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
====Chemotherapy, CEX portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Capecitabine (Xeloda)]] 900 mg/m<sup>2</sup> PO twice per day on days 1 to 15
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
 
 
−
===References===
 
−
# '''FinXX:''' Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Asola R, Kokko R, Ahlgren J, Auvinen P, Hemminki A, Paija O, Helle L, Nuortio L, Villman K, Nilsson G, Lahtela SL, Lehtiö K, Pajunen M, Poikonen P, Nyandoto P, Kataja V, Bono P, Leinonen M, Lindman H; FinXX Study Investigators. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial. Lancet Oncol. 2009 Dec;10(12):1145-51. Epub 2009 Nov 10. [https://doi.org/10.1016/s1470-2045(09)70307-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19906561 PubMed] NCT00114816
 
−
## '''Update:''' Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Paija O, Helle L, Villman K, Nyandoto P, Nilsson G, Pajunen M, Asola R, Poikonen P, Leinonen M, Kataja V, Bono P, Lindman H. Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial. J Clin Oncol. 2012 Jan 1;30(1):11-8. Epub 2011 Nov 21. [https://doi.org/10.1200/JCO.2011.35.4639 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22105826 PubMed]
 
−
## '''Update:''' Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola A, Tanner M, Ahlgren J, Auvinen P, Lahdenperä O, Villman K, Nyandoto P, Nilsson G, Poikonen-Saksela P, Kataja V, Bono P, Junnila J, Lindman H. Adjuvant Capecitabine for Early Breast Cancer: 15-Year Overall Survival Results From a Randomized Trial. J Clin Oncol. 2022 Apr 1;40(10):1051-1058. Epub 2022 Jan 12. [https://doi.org/10.1200/jco.21.02054 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966968/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35020465/ PubMed]
 
−
 
 
−
=Adjuvant chemotherapy=
 
−
==Bevacizumab monotherapy {{#subobject:c254bd|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:6c056e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401076/ Bear et al. 2012 (NSABP B-40)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#NSABP_B-40|See link]]
 
−
|[[Complex_multipart_regimens#NSABP_B-40|See link]]
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*Neoadjuvant [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_.26_Bevacizumab|AC+Bev]] x 4, then [[Surgery#Breast_cancer_surgery|surgery]]
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycle for 10 cycles'''
 
−
===References===
 
−
# '''NSABP B-40:''' Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. [https://doi.org/10.1056/NEJMoa1111097 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401076/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22276821 PubMed] NCT00408408
 
−
## '''Update:''' Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. [https://doi.org/10.1016/S1470-2045(15)00041-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624323/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26272770 PubMed]
 
−
 
 
−
==Capecitabine monotherapy {{#subobject:e058c1|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, 4 cycles {{#subobject:36e4ba|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489700/ Cameron et al. 2017 (TACT2)]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[Complex_multipart_regimens#TACT2|See link]]
 
−
| style="background-color:#eeee01" |[[Complex_multipart_regimens#TACT2|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*ddE x 4 versus [[#Epirubicin_monotherapy|Epirubicin]] x 4
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===Regimen variant #2, 6 to 8 cycles {{#subobject:9cc782|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082436/ Muss et al. 2009 (CALGB 49907)]
 
−
|2001-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|Physician's choice of:<br> 1. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4<br> 2. [[#CMF|CMF]] x 6
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1612645 Masuda et al. 2017 (CREATE-X)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|Standard therapy
 
−
| style="background-color:#1a9850" |Superior OS<br>OS60: 89.2% vs 83.6%<br>(HR 0.59, 95% CI 0.39-0.90)
 
−
|-
 
−
|}
 
−
''Note: patients in CALGB 49907 received a maximum of 6 cycles. All patients in CREATE-X had residual disease at time of surgical resection. Concomitant endocrine therapy was allowed.''
 
−
====Preceding treatment====
 
−
*CALGB 49907: [[Surgery#Breast_cancer_surgery|Surgery]]
 
−
*CREATE-X: Neoadjuvant [[Regimen_classes#Chemotherapy|chemotherapy]] containing anthracycline, taxane, or both, then [[Surgery#Breast_cancer_surgery|surgery]]
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
 
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
 
 
−
===References===
 
−
# '''CALGB 49907:''' Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Becker HP, Kartcheske PA, Wheeler JD, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Magrinat G, Parker BA, Hart RD, Grenier D, Norton L, Hudis CA, Winer EP; CALGB. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009 May 14;360(20):2055-65. Erratum in: N Engl J Med. 2009 Oct 22;361(17):1714. Magrinat, Gutav [corrected to Magrinat, Gustav]. [https://doi.org/10.1056/NEJMoa0810266 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082436/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19439741 PubMed] NCT00024102
 
−
# '''CREATE-X:''' Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, Kuroi K, Im SA, Park BW, Kim SB, Yanagita Y, Ohno S, Takao S, Aogi K, Iwata H, Jeong J, Kim A, Park KH, Sasano H, Ohashi Y, Toi M. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017 Jun 1;376(22):2147-2159. [https://doi.org/10.1056/NEJMoa1612645 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28564564 PubMed] UMIN000000843
 
−
# '''TACT2:''' Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, Agrawal R, Banerji J, Bertelli G, Bloomfield D, Brunt AM, Earl H, Ellis P, Gaunt C, Gillman A, Hearfield N, Laing R, Murray N, Couper N, Stein RC, Verrill M, Wardley A, Barrett-Lee P, Bliss JM; TACT2 Investigators. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2017 Jul;18(7):929-945. Epub 2017 Jun 7. [https://doi.org/10.1016/S1470-2045(17)30404-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489700/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28600210 PubMed] NCT00301925
 
−
 
 
−
==CMF {{#subobject:fb4c46|Regimen=1}}==
 
−
 
 
−
CMF: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
−
===Regimen variant #1, 600/40/600 x 6 {{#subobject:92cca2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://insights.ovid.com/pubmed?pmid=11474254 Ron et al. 2001]
 
−
|1988-1992
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer_-_historical#FNC|CNF]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #2, 600/40/600 x 8 {{#subobject:93cae2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1991.9.12.2134 Buzzoni et al. 1991 (Milan trial)]
 
−
|1982-1987
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#Buzzoni_et_al._1991|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#Buzzoni_et_al._1991|See link]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199710023371401 Overgaard et al. 1997 (DBCG 82b)]
 
−
|1982-1989
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[Complex_multipart_regimens#DBCG_82b|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#DBCG_82b|See link]]
 
−
|-
 
−
|}
 
−
''Note: in DBCG 82b, radiotherapy was given between cycles 1 & 2
 
−
====Preceding treatment====
 
−
*Milan trial: [[Surgery#Breast_cancer_surgery|Surgery]], then [[#Doxorubicin_monotherapy|A]] x 4
 
−
*DBCG 82b: [[Surgery#Mastectomy|Mastectomy]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #3, 600/50/600 x 8 {{#subobject:93cae2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/96/14/1076/2520847 Leonard et al. 2004]
 
−
|1995-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Thiotepa.2C_then_auto_HSCT_99|Cyclophosphamide & Thiotepa with auto HSCT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[#Doxorubicin_monotherapy|A]] x 4
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #4, 700/30/700 x 24 {{#subobject:8ba32c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1995.13.1.33 Clahsen et al. 1995 (EORTC 09771)]
 
−
|1976-1980
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 350 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''1-month cycle for 24 cycles'''
 
−
 
 
−
===Regimen variant #5, 750/50/600 x 6-8 ("Scottish Breast Group schedule") {{#subobject:7a96ee|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/0140-6736(93)90812-U Stewart et al. 1993]
 
−
|1980-1990
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Breast_cancer_-_historical#CMFP|CMFP]]<br>2. [[Endocrine_ablation_surgery#Bilateral_oophorectomy|Oophorectomy]]<br>3. [[#Oophorectomy_.26_Prednisolone_99|Oophorectomy & Prednisolone]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa052084 Poole et al. 2006 (BR9601)]
 
−
|1996-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#E-CMF|E-CMF]] x 4+4
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ Fernando et al. 2019 (SECRAB)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CMF_.26_RT_88|CMF & RT]]<br>2. [[#E-CMF_.26_RT_88|E-CMF & RT]]<br>3. [[#A-CMF_.26_RT_88|A-CMF & RT]]<br>4. [[#MMM_.26_RT_88|MMM & RT]]
 
−
| style="background-color:#d73027" |Inferior LRFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
 
 
−
===Regimen variant #6, 840/50/800 {{#subobject:17bzcj|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://www.surgjournal.com/article/0039-6060(80)90244-5 Hubay et al. 1980]
 
−
|rowspan=2|NR
 
−
|rowspan=2 style="background-color:#1a9851" |Randomized (C)
 
−
|1. [[#CMFT|CMFT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior RFS
 
−
|-
 
−
|2. [[#CMFT_.26_BCG_99|CMFT & BCG]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of RFS/OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 30 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 12 cycles'''
 
−
 
 
−
===Regimen variant #7, 1000/80/1000 x 6 {{#subobject:8abc32|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s12282-009-0132-x Kimura et al. 2009]
 
−
|1996-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_2|FEC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #8, 1000/80/1200 x 3 {{#subobject:a2edc8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.07.026 Zander et al. 2004]
 
−
|1993-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide.2C_Mitoxantrone.2C_Thiotepa.2C_then_auto_HSCT_88|Cyclophosphamide, Mitoxantrone, Thiotepa with auto HSCT]]
 
−
| style="background-color:#fee08b" |Might have inferior EFS
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[#Cyclophosphamide_.26_Epirubicin_.28EC.29|EC]] x 4
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 3 cycles'''
 
−
 
 
−
===Regimen variant #9, 1000/80/1200 x 6 {{#subobject:831237|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2002.05.042 Jonat et al. 2002 (ZEBRA)]
 
−
|1990-1996
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Goserelin_monotherapy_99|Goserelin]] x 2 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.08.8534 Schmid et al. 2007 (TABLE)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer,_ER-positive#Leuprolide_monotherapy|Leuprolide]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], within 6 weeks
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #10, 1120/60/1000 x 12 {{#subobject:61d518|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=3|[https://doi.org/10.1007/BF01806239 Brincker et al. 1983 (DBCG 77B)]
 
−
|rowspan=3|1977-1983
 
−
|rowspan=3 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[Breast_cancer_-_historical#Cyclophosphamide_monotherapy|Cyclophosphamide]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|2. [[Breast_cancer_-_historical#Levamisole_monotherapy|Levamisole]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|3. [[Breast_cancer_-_null_regimens#Observation|No chemotherapy]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy versus no chemotherapy is based on the 2010 update.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 80 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''1-month cycle for 12 cycles'''
 
−
 
 
−
===Regimen variant #11, 1120/64/960 x 12 {{#subobject:611b18|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(84)92684-9 Howell et al. 1984]
 
−
|1976-1983
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior RFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 80 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 32 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 4800 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 12 cycles'''
 
−
 
 
−
===Regimen variant #12, 1200/80/1200 x 4 {{#subobject:37c8be|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2008.19.2567 Gianni et al. 2009 (ECTO)]
 
−
|1996-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#ECTO|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#ECTO|See link]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdu564 Perrone et al. 2014 (ELDA)]
 
−
|2003-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_monotherapy|Docetaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. In ELDA, this protocol was for ER/PR+ patients.''
 
−
====Preceding treatment====
 
−
*ECTO: [[Surgery#Breast_cancer_surgery|Surgery]], then [[#Doxorubicin_monotherapy|A]] x 4 versus [[#Doxorubicin_.26_Paclitaxel_.28AT.29|AT (Taxol)]] x 4
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 4 cycles'''
 
−
 
 
−
===Regimen variant #13, 1200/80/1200 x 6 ("Classical" IV) {{#subobject:958ae2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199710023371402 Ragaz et al. 1997]
 
−
|1978-1986
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMF_.26_RT_88|CMF & RT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.1.35 Coombes et al. 1996]
 
−
|1984-1992
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_2|FEC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of RFS/OS
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-007-9844-9 Taucher et al. 2007 (ABCSG-07)]
 
−
|1991-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMF_99|CMF]]; neoadjuvant
 
−
| style="background-color:#91cf60" |Seems to have superior RFS
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa052084 Poole et al. 2006 (NEAT)]
 
−
|1996-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#E-CMF|E-CMF]] x 4+4
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ Fernando et al. 2019 (SECRAB)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CMF_.26_RT_88|CMF & RT]]<br>2. [[#E-CMF_.26_RT_88|E-CMF & RT]]<br>3. [[#A-CMF_.26_RT_88|A-CMF & RT]]<br>4. [[#MMM_.26_RT_88|MMM & RT]]
 
−
| style="background-color:#d73027" |Inferior LRFS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdu564 Perrone et al. 2014 (ELDA)]
 
−
|2003-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_monotherapy|Docetaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''Note: In ELDA, this protocol was for ER/PR- patients.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #14, 1400/60/1200 x 12 {{#subobject:d1gh15|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/0277-5379(89)90203-4 Rubens et al. 1989 (EORTC 10792)]
 
−
|rowspan=2|1979-1985
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
−
|-
 
−
|2. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]<br>3. [[#CMFT|CMFT]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
''Note: this trial had a complex efficacy analysis; see paper for details.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 12 cycles'''
 
−
 
 
−
===Regimen variant #15, 1400/80/1000 x 6 {{#subobject:d1abf4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2008.18.3939 Watanabe et al. 2009 (NSAS BC-01)]
 
−
|1996-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#UFT_monotherapy_99|UFT]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior RFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #16, 1400/80/1200 x 3 {{#subobject:16ad91|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan = 2|[https://doi.org/10.1200/JCO.1996.14.6.1885 Castiglione-Gertsch et al. 1996 (IBCSG VI)]
 
−
|rowspan = 2|1986-1993
 
−
|rowspan = 2 style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#CMF|CMF]] x 6
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
−
|-
 
−
|2. [[#CMF|CMF]] x 3, with re-introduction<br>3. [[#CMF|CMF]] x 6, with re-introduction
 
−
| style="background-color:#fee08b" |Might have inferior DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*IBCSG VI: [[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 3 cycles'''
 
−
====Subsequent treatment====
 
−
*IBCSG VI: [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 y versus [[Breast_cancer_-_null_regimens#Observation|no further treatment]]
 
−
 
 
−
===Regimen variant #18, 1400/80/1200 x 6 {{#subobject:dcd1f4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/394864 Tancini et al. 1979]
 
−
|1975-NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#CMF|CMF]] x 12
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.1.35 Coombes et al. 1996]
 
−
|1984-1992
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_2|FEC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of RFS/OS
 
−
|-
 
−
|rowspan = 2|[https://doi.org/10.1200/JCO.1996.14.6.1885 Castiglione-Gertsch et al. 1996 (IBCSG VI)]
 
−
|rowspan = 2|1986-1993
 
−
|rowspan = 2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CMF|CMF]] x 3
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|2. [[#CMF|CMF]] x 3, with re-introduction<br> 3. [[#CMF|CMF]] x 6, with re-introduction
 
−
| style="background-color:#fee08b" |Might have inferior DFS
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2001.19.12.3103 Piccart et al. 2001 (Belgian trial)]
 
−
|rowspan=2|1988-1996
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Cyclophosphamide_.26_Epirubicin_.28EC.29|EC]]; full-dose
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|2. [[#Cyclophosphamide_.26_Epirubicin_.28EC.29|EC]]; moderate-dose
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1998.16.8.2651 Levine et al. 1998 (NCIC-CTG MA.5)]
 
−
|1989-1993
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_2|CEF]]
 
−
| style="background-color:#d73027" |Inferior RFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.17.3125 Amadori et al. 2000]
 
−
|1989-1993
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.08.071 Hutchins et al. 2005 (INT-0102)]
 
−
|1989-1993
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FAC_2|CAF]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2002.05.042 Jonat et al. 2002 (ZEBRA)]
 
−
|1990-1996
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Goserelin_monotherapy_99|Goserelin]] x 2 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2001.19.4.931 Fisher et al. 2001 (NSABP B-23)]
 
−
|1991-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29|AC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1093/jnci/djk108 Adjuvant Breast Cancer Trials Collaborative Group 2007 (NCRI ABC-CT)]
 
−
|1992-2000
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>(aHR 0.83, 95% CI 0.70-0.99)
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa052084 Poole et al. 2006 (NEAT)]
 
−
|1996-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#E-CMF|E-CMF]] x 4+4
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ Fernando et al. 2019 (SECRAB)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CMF_.26_RT_88|CMF & RT]]<br>2. [[#E-CMF_.26_RT_88|E-CMF & RT]]<br>3. [[#A-CMF_.26_RT_88|A-CMF & RT]]<br>4. [[#MMM_.26_RT_88|MMM & RT]]
 
−
| style="background-color:#d73027" |Inferior LRFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082436/ Muss et al. 2009 (CALGB 49907)]
 
−
|2001-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_monotherapy|Capecitabine]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
====Subsequent treatment====
 
−
*NSABP B-23 and INT-0102: [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|tamoxifen]] x 5 years versus [[Breast_cancer_-_null_regimens#Placebo|placebo]]
 
−
 
 
−
===Regimen variant #19, 1400/80/1200 x 12 {{#subobject:8a712c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM197602192940801 Bonadonna et al. 1976]
 
−
|1973-1975
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior RFS
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/394864 Tancini et al. 1979]
 
−
|1975-NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMF|CMF]] x 6
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.4.1136 Misset et al. 1996 (OncoFrance)]
 
−
|1978-1981
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer_-_historical#AVCF|AVCF]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q Tormey et al. 1990 (ECOG E5177)]
 
−
|1978-1982
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Breast_cancer_-_historical#CMFP|CMFP]]<br> 2. [[Breast_cancer_-_historical#CMFPT|CMFPT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of TTR/OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 12 cycles'''
 
−
 
 
−
===References===
 
−
# Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, De Lena M, Tancini G, Bajetta E, Musumeci R, Veronesi U. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976 Feb 19;294(8):405-10. [https://doi.org/10.1056/NEJM197602192940801 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1246307 PubMed]
 
−
## '''Update:''' Bonadonna G, Rossi A, Valagussa P, Banfi A, Veronesi U. The CMF program for operable breast cancer with positive axillary nodes: updated analysis on the disease-free interval, site of relapse and drug tolerance. Cancer. 1977 Jun;39(6 Suppl):2904-15. [https://doi.org/10.1002/1097-0142(197706)39:6%3C2904::AID-CNCR2820390677%3E3.0.CO;2-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/326384 PubMed]
 
−
## '''Update:''' Bonadonna G, Valagussa P, Rossi A, Tancini G, Brambilla C, Zambetti M, Veronesi U. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat. 1985;5(2):95-115. [https://doi.org/10.1007/bf01805984 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3839424 PubMed]
 
−
## '''Update:''' Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995 Apr 6;332(14):901-6. [https://www.nejm.org/doi/ref/10.1056/NEJM199504063321401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7877646 PubMed]
 
−
# Tancini G, Bajetta E, Marchini S, Valagussa P, Bonadonna G, Veronesi U. Preliminary 3-year results of 12 versus 6 cycles of surgical adjuvant CMF in premenopausal breast cancer. Cancer Clin Trials. 1979 Winter;2(4):285-92. [https://pubmed.ncbi.nlm.nih.gov/394864 PubMed]
 
−
## '''Update:''' Tancini G, Bonadonna G, Valagussa P, Marchini S, Veronesi U. Adjuvant CMF in breast cancer: comparative 5-year results of 12 versus 6 cycles. J Clin Oncol. 1983 Jan;1(1):2-10. [https://doi.org/10.1200/JCO.1983.1.1.2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6366125 PubMed]
 
−
# Hubay CA, Pearson OH, Marshall JS, Rhodes RS, Debanne SM, Mansour EG, Hermann RE, Jones JC, Flynn WJ, Eckert C, McGuire WL. Antiestrogen, cytotoxic chemotherapy, and bacillus Calmette-Guerin vaccination in stage II breast cancer: a preliminary report. Surgery. 1980 May;87(5):494-501. [https://www.surgjournal.com/article/0039-6060(80)90244-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7368100 PubMed]
 
−
## '''Update:''' Hubay CA, Pearson OH, Marshall JS, Rhodes RS, DeBanne SM, Rosenblatt J, Mansour EG, Hermann RE, Jones JC, Flynn WJ, Eckert C, McGuire WL. Adjuvant chemotherapy, antiestrogen therapy and immunotherapy for stage II breast cancer: 45-month follow-up of a prospective, randomized clinical trial. Cancer. 1980 Dec 15;46(12 Suppl):2805-8. [https://doi.org/10.1002/1097-0142(19801215)46:12%2B%3C2805::AID-CNCR2820461413%3E3.0.CO;2-H link to original article] [https://pubmed.ncbi.nlm.nih.gov/7004624 PubMed]
 
−
# '''DBCG 77B:''' Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. [https://doi.org/10.1007/BF01806239 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6347278 PubMed]
 
−
## '''Update:''' Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Andersson M, Kamby C, Knoop AS; Danish Breast Cancer Cooperative Group. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer. Cancer. 2010 May 1;116(9):2081-9. [https://doi.org/10.1002/cncr.24969 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20186830 PubMed]
 
−
# Howell A, Bush H, George WD, Howat JM, Crowther D, Sellwood RA, Rubens RD, Hayward JL, Bulbrook RD, Fentiman IS, Chaudary M. Controlled trial of adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil for breast cancer. Lancet. 1984 Aug 11;2(8398):307-11. [https://doi.org/10.1016/S0140-6736(84)92684-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6146861 PubMed]
 
−
# '''ECOG E5177:''' Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. [https://doi.org/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2403834 PubMed]
 
−
# '''Milan trial:''' Buzzoni R, Bonadonna G, Valagussa P, Zambetti M. Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil in the treatment of resectable breast cancer with more than three positive axillary nodes. J Clin Oncol. 1991 Dec;9(12):2134-40. [https://doi.org/10.1200/JCO.1991.9.12.2134 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1960555 PubMed]
 
−
## '''Update:''' Bonadonna G, Zambetti M, Valagussa P. Sequential or alternating doxorubicin and CMF regimens in breast cancer with more than three positive nodes: ten-year results. JAMA. 1995 Feb 15;273(7):542-7. [https://jamanetwork.com/journals/jama/fullarticle/387001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7837388 PubMed]
 
−
# Stewart HJ, Forrest APM, Hawkins RA, Prescott RJ, Smith DC, Everington D, Richards MA, George WD; Scottish Cancer Trials Breast Group and ICRF Breast Unit Guy's Hospital London. Adjuvant ovarian ablation versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: the Scottish trial. Lancet. 1993 May 22;341(8856):1293-8. [https://doi.org/10.1016/0140-6736(93)90812-U link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8098446 PubMed]
 
−
# '''EORTC 09771:''' Clahsen PC, van de Velde CJ, Welvaart K, Repelaer van Driel OJ, Sylvester RJ; Cooperating Investigators. Ten-year results of a randomized trial evaluating prolonged low-dose adjuvant chemotherapy in node-positive breast cancer: a joint European Organisation for Research and Treatment of Cancer-Dutch Breast Cancer Working Party Study. J Clin Oncol. 1995 Jan;13(1):33-41. [https://doi.org/10.1200/JCO.1995.13.1.33 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7799039 PubMed]
 
−
# Coombes RC, Bliss JM, Wils J, Morvan F, Espié M, Amadori D, Gambrosier P, Richards M, Aapro M, Villar-Grimalt A, McArdle C, Pérez-López FR, Vassilopoulos P, Ferreira EP, Chilvers CE, Coombes G, Woods EM, Marty M; International Collaborative Cancer Group. Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. J Clin Oncol. 1996 Jan;14(1):35-45. [https://doi.org/10.1200/JCO.1996.14.1.35 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8558217 PubMed]
 
−
# '''OncoFrance:''' Misset JL, di Palma M, Delgado M, Plagne R, Chollet P, Fumoleau P, Le Mevel B, Belpomme D, Guerrin J, Fargeot P, Metz R, Ithzaki M, Hill C, Mathé G. Adjuvant treatment of node-positive breast cancer with cyclophosphamide, doxorubicin, fluorouracil, and vincristine versus cyclophosphamide, methotrexate, and fluorouracil: final report after a 16-year median follow-up duration. J Clin Oncol. 1996 Apr;14(4):1136-45. [https://doi.org/10.1200/JCO.1996.14.4.1136 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8648368 PubMed]
 
−
# '''IBCSG VI:''' Castiglione-Gertsch M, Goldhirsch A; International Breast Cancer Study Group. Duration and reintroduction of adjuvant chemotherapy for node-positive premenopausal breast cancer patients. J Clin Oncol. 1996 Jun;14(6):1885-94. [https://doi.org/10.1200/JCO.1996.14.6.1885 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8656257 PubMed]
 
−
## '''Pooled QoL analysis:''' Hürny C, Bernhard J, Coates AS, Castiglione-Gertsch M, Peterson HF, Gelber RD, Forbes JF, Rudenstam CM, Simoncini E, Crivellari D, Goldhirsch A, Senn HJ; International Breast Cancer Study Group. Impact of adjuvant therapy on quality of life in women with node-positive operable breast cancer. Lancet. 1996 May 11;347(9011):1279-84. Erratum in: Lancet 1997 Jul 26;350(9073):298. [https://doi.org/10.1016/S0140673696909368 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8622502 PubMed]
 
−
#'''EORTC 10792:''' Rubens RD, Bartelink H, Engelsman E, Hayward JL, Rotmensz N, Sylvester R, van der Schueren E, Papadiamantis J, Vassilaros SD, Wildiers J, et al. Locally advanced breast cancer: the contribution of cytotoxic and endocrine treatment to radiotherapy - an EORTC Breast Cancer Co-operative Group Trial (10792). Eur J Cancer Clin Oncol. 1989 Apr;25(4):667-78. [https://doi.org/10.1016/0277-5379(89)90203-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2653846/ PubMed]
 
−
##'''Update:''' Bartelink H, Rubens RD, van der Schueren E, Sylvester R. Hormonal therapy prolongs survival in irradiated locally advanced breast cancer: a European Organization for Research and Treatment of Cancer Randomized Phase III Trial. J Clin Oncol. 1997 Jan;15(1):207-15. [https://doi.org/10.1200/jco.1997.15.1.207 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8996144/ PubMed]
 
−
# '''DBCG 82b:''' Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy: Danish Breast Cancer Cooperative Group 82b trial. N Engl J Med. 1997 Oct 2;337(14):949-55. [https://doi.org/10.1056/NEJM199710023371401 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9395428 PubMed]
 
−
# Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE, Wilson KS, Knowling MA, Coppin CM, Paradis M, Coldman AJ, Olivotto IA. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. 1997 Oct 2;337(14):956-62. [https://doi.org/10.1056/NEJM199710023371402 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9309100 PubMed]
 
−
# '''Review:''' Goldhirsch A, Colleoni M, Coates AS, Castiglione-Gertsch M, Gelber RD; International Breast Cancer Study Group. Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all CMFs alike?. Ann Oncol. 1998 May;9(5):489-93. [https://doi.org/10.1023/a:1008236502420 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9653488 PubMed]
 
−
# '''NCIC-CTG MA.5:''' Levine MN, Bramwell VH, Pritchard KI, Norris BD, Shepherd LE, Abu-Zahra H, Findlay B, Warr D, Bowman D, Myles J, Arnold A, Vandenberg T, MacKenzie R, Robert J, Ottaway J, Burnell M, Williams CK, Tu D; National Cancer Institute of Canada Clinical Trials Group. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. J Clin Oncol. 1998 Aug;16(8):2651-8. [https://doi.org/10.1200/jco.1998.16.8.2651 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9704715 PubMed]
 
−
## '''Update:''' Levine MN, Pritchard KI, Bramwell VH, Shepherd LE, Tu D, Paul N; National Cancer Institute of Canada Clinical Trials Group. Randomized trial comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials Group Trial MA5. J Clin Oncol. 2005 Aug 1;23(22):5166-70. [https://doi.org/10.1200/JCO.2005.09.423 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16051958 PubMed]
 
−
## '''Subgroup analysis:''' Pritchard KI, Shepherd LE, O'Malley FP, Andrulis IL, Tu D, Bramwell VH, Levine MN; National Cancer Institute of Canada Clinical Trials Group. HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med. 2006 May 18;354(20):2103-11. [https://doi.org/10.1056/NEJMoa054504 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16707747 PubMed]
 
−
# Amadori D, Nanni O, Marangolo M, Pacini P, Ravaioli A, Rossi A, Gambi A, Catalano G, Perroni D, Scarpi E, Giunchi DC, Tienghi A, Becciolini A, Volpi A. Disease-free survival advantage of adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with node-negative, rapidly proliferating breast cancer: a randomized multicenter study. J Clin Oncol. 2000 Sep;18(17):3125-34. [https://doi.org/10.1200/JCO.2000.18.17.3125 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10963641 PubMed]
 
−
## '''Update:''' Amadori D, Nanni O, Volpi A, Casadei Giunchi D, Marangolo M, Livi L, Ravaioli A, Rossi AP, Gambi A, Luzi Fedeli S, Perroni D, Scarpi E, Becciolini A, Silvestrini R. Phase III randomized multicenter study on the effects of adjuvant CMF in patients with node-negative, rapidly proliferating breast cancer: twelve-year results and retrospective subgroup analysis. Breast Cancer Res Treat. 2008 Mar;108(2):259-64. Epub 2007 May 26. [https://doi.org/10.1007/s10549-007-9593-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17530429 PubMed]
 
−
# '''NSABP B-23:''' Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. [https://doi.org/10.1200/jco.2001.19.4.931 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11181655 PubMed]
 
−
# '''Belgian trial:''' Piccart MJ, Di Leo A, Beauduin M, Vindevoghel A, Michel J, Focan C, Tagnon A, Ries F, Gobert P, Finet C, Closon-Dejardin MT, Dufrane JP, Kerger J, Liebens F, Beauvois S, Bartholomeus S, Dolci S, Lobelle JP, Paesmans M, Nogaret JM. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001 Jun 15;19(12):3103-10. [https://doi.org/10.1200/jco.2001.19.12.3103 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11408507 PubMed]
 
−
## '''Update:''' de Azambuja E, Paesmans M, Beauduin M, Vindevoghel A, Cornez N, Finet C, Ries F, Closon-Dejardin MT, Kerger J, Gobert P, Focan C, Tagnon A, Dolci S, Nogaret JM, di Leo A, Piccart-Gebhart MJ. Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node-positive breast cancer: 15-year efficacy results of the Belgian multicentre study. J Clin Oncol. 2009 Feb 10;27(5):720-5. Epub 2008 Dec 22. [https://doi.org/10.1200/JCO.2008.17.2155 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19103732 PubMed]
 
−
# Ron IG, Wigler N, Borovik R, Brufman G, Rizel S, Shani A, Brenner J, Farbstein H, Dale A, Inbar MJ, Brenner HJ, Chaitchik S, Catane R. CMF (cyclophosphamide, methotrexate, 5-fluorouracil) versus CNF (cyclophosphamide, mitoxantrone, 5-fluorouracil) as adjuvant chemotherapy for stage II lymph-node positive breast  cancer: a phase III randomized multicenter study. Am J Clin Oncol. 2001 Aug;24(4):323-7. [https://insights.ovid.com/pubmed?pmid=11474254 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11474254 PubMed]
 
−
# '''ZEBRA:''' Jonat W, Kaufmann M, Sauerbrei W, Blamey R, Cuzick J, Namer M, Fogelman I, de Haes JC, de Matteis A, Stewart A, Eiermann W, Szakolczai I, Palmer M, Schumacher M, Geberth M, Lisboa B; Zoladex Early Breast Cancer Research Association Study. Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: the Zoladex Early Breast Cancer Research Association study. J Clin Oncol. 2002 Dec 15;20(24):4628-35. [https://doi.org/10.1200/JCO.2002.05.042 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488406 PubMed]
 
−
# Zander AR, Kröger N, Schmoor C, Krüger W, Möbus V, Frickhofen N, Metzner B, Schultze W, Berdel WE, Koenigsmann M, Thiel E, Wandt H, Possinger K, Trümper L, Kreienberg R, Carstensen M, Schmidt EH, Jänicke F, Schumacher M, Jonat W. High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: first results of a randomized trial. J Clin Oncol. 2004 Jun 15;22(12):2273-83. Epub 2004 Apr 26. [https://doi.org/10.1200/JCO.2004.07.026 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15111618 PubMed]
 
−
# Leonard RC, Lind M, Twelves C, Coleman R, van Belle S, Wilson C, Ledermann J, Kennedy I, Barrett-Lee P, Perren T, Verrill M, Cameron D, Foster E, Yellowlees A, Crown J; Anglo-Celtic Cooperative Oncology Group. Conventional adjuvant chemotherapy versus single-cycle, autograft-supported, high-dose, late-intensification chemotherapy in high-risk breast cancer patients: a randomized trial. J Natl Cancer Inst. 2004 Jul 21;96(14):1076-83. [https://academic.oup.com/jnci/article/96/14/1076/2520847 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15265969 PubMed]
 
−
# '''INT-0102:''' Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of intergroup protocol INT-0102. J Clin Oncol. 2005 Nov 20;23(33):8313-21. [https://doi.org/10.1200/jco.2005.08.071 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16293862 PubMed]
 
−
<!-- no pre-pub disclosed -->
 
−
# '''NEAT:''' Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. [https://doi.org/10.1056/nejmoa052084 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17079759 PubMed] NCT00003577
 
−
## '''Update:''' Earl HM, Hiller L, Dunn JA, Vallier AL, Bowden SJ, Jordan SD, Blows F, Munro A, Bathers S, Grieve R, Spooner DA, Agrawal R, Fernando I, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, McAdam K, Foster L, Leonard RC, Twelves CJ, Cameron D, Bartlett JM, Pharoah P, Provenzano E, Caldas C, Poole CJ; NEAT Investigators and the SCTBG. Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials. Br J Cancer. 2012 Oct 9;107(8):1257-67. Epub 2012 Sep 11. [https://doi.org/10.1038/bjc.2012.370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494422/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23047592 PubMed]
 
−
<!-- no pre-pub disclosed -->
 
−
# '''BR9601:''' Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. [https://doi.org/10.1056/nejmoa052084 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17079759 PubMed] NCT00003012
 
−
## '''Update:''' Earl HM, Hiller L, Dunn JA, Vallier AL, Bowden SJ, Jordan SD, Blows F, Munro A, Bathers S, Grieve R, Spooner DA, Agrawal R, Fernando I, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, McAdam K, Foster L, Leonard RC, Twelves CJ, Cameron D, Bartlett JM, Pharoah P, Provenzano E, Caldas C, Poole CJ; NEAT Investigators and the SCTBG. Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials. Br J Cancer. 2012 Oct 9;107(8):1257-67. Epub 2012 Sep 11. [https://doi.org/10.1038/bjc.2012.370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494422/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23047592 PubMed]
 
−
# '''DBCG 89D:''' Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Cold S, Edlund P, Ewertz M, Jensen BB, Kamby C, Nordenskjold B, Bergh J. Improved outcome from substituting methotrexate with epirubicin: results from a randomised comparison of CMF versus CEF in patients with primary breast cancer. Eur J Cancer. 2007 Mar;43(5):877-84. Epub 2007 Feb 16. [https://www.ejcancer.com/article/S0959-8049(07)00014-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17306974 PubMed]
 
−
# '''NCRI ABC-CT:''' Adjuvant Breast Cancer Trials Collaborative Group. Polychemotherapy for early breast cancer: results from the international adjuvant breast cancer chemotherapy randomized trial. J Natl Cancer Inst. 2007 Apr 4;99(7):506-15. [https://doi.org/10.1093/jnci/djk108 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17405995/ PubMed] NCT00002582
 
−
<!-- Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 18-21, 2002; the San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003; the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004; and the San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-11, 2004. -->
 
−
# '''TABLE:''' Schmid P, Untch M, Kossé V, Bondar G, Vassiljev L, Tarutinov V, Lehmann U, Maubach L, Meurer J, Wallwiener D, Possinger K. Leuprorelin acetate every-3-months depot versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant treatment in premenopausal patients with node-positive breast cancer: the TABLE study. J Clin Oncol. 2007 Jun 20;25(18):2509-15. [https://doi.org/10.1200/jco.2006.08.8534 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17577027 PubMed]
 
−
# '''ABCSG-07:''' Taucher S, Steger GG, Jakesz R, Tausch C, Wette V, Schippinger W, Kwasny W, Reiner G, Greil R, Dubsky P, Poestlberger S, Tschmelitsch J, Samonigg H, Gnant M; ABCSG. The potential risk of neoadjuvant chemotherapy in breast cancer patients--results from a prospective randomized trial of the Austrian Breast and Colorectal Cancer Study Group (ABCSG-07). Breast Cancer Res Treat. 2008 Nov;112(2):309-16. Epub 2007 Dec 14. [https://doi.org/10.1007/s10549-007-9844-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18080748 PubMed]
 
−
# '''NSAS BC-01:''' Watanabe T, Sano M, Takashima S, Kitaya T, Tokuda Y, Yoshimoto M, Kohno N, Nakagami K, Iwata H, Shimozuma K, Sonoo H, Tsuda H, Sakamoto G, Ohashi Y. Oral uracil and tegafur compared with classic cyclophosphamide, methotrexate, fluorouracil as postoperative chemotherapy in patients with node-negative, high-risk breast cancer: National Surgical Adjuvant Study for Breast Cancer 01 trial. J Clin Oncol. 2009 Mar 20;27(9):1368-74. Epub 2009 Feb 9. [https://doi.org/10.1200/JCO.2008.18.3939 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19204202 PubMed] NCT00152191
 
−
# '''ECTO:''' Gianni L, Baselga J, Eiermann W, Porta VG, Semiglazov V, Lluch A, Zambetti M, Sabadell D, Raab G, Cussac AL, Bozhok A, Martinez-Agulló A, Greco M, Byakhov M, Lopez JJ, Mansutti M, Valagussa P, Bonadonna G. Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol. 2009 May 20;27(15):2474-81. Epub 2009 Mar 30. [https://doi.org/10.1200/JCO.2008.19.2567 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19332727 PubMed] NCT00003013
 
−
# '''TACT:''' Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. [https://doi.org/10.1016/S0140-6736(09)60740-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687939/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19447249 PubMed] ISRCTN79718493
 
−
# '''CALGB 49907:''' Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Becker HP, Kartcheske PA, Wheeler JD, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Magrinat G, Parker BA, Hart RD, Grenier D, Norton L, Hudis CA, Winer EP; CALGB. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009 May 14;360(20):2055-65. Erratum in: N Engl J Med. 2009 Oct 22;361(17):1714. Magrinat, Gutav [corrected to Magrinat, Gustav]. [https://doi.org/10.1056/NEJMoa0810266 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082436/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19439741 PubMed] NCT00024102
 
−
# Kimura M, Tominaga T, Takatsuka Y, Toi M, Abe R, Koyama H, Takashima S, Nomura Y, Miura S, Kimijima I, Tashiro H, Ohashi Y; Adjuvant CEF Research Group for Breast Cancer. Randomized trial of cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil with node-positive breast cancer in Japan. Breast Cancer. 2010 Jul;17(3):190-8. Epub 2009 Jul 3. [https://doi.org/10.1007/s12282-009-0132-x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19575284 PubMed]
 
−
# '''ELDA:''' Perrone F, Nuzzo F, Di Rella F, Gravina A, Iodice G, Labonia V, Landi G, Pacilio C, Rossi E, De Laurentiis M, D'Aiuto M, Botti G, Forestieri V, Lauria R, De Placido S, Tinessa V, Daniele B, Gori S, Colantuoni G, Barni S, Riccardi F, De Maio E, Montanino A, Morabito A, Daniele G, Di Maio M, Piccirillo MC, Signoriello S, Gallo C, de Matteis A. Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial. Ann Oncol. 2015 Apr;26(4):675-82. Epub 2014 Dec 8. [https://doi.org/10.1093/annonc/mdu564 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25488686 PubMed] NCT00331097
 
−
# '''SECRAB:''' Fernando IN, Bowden SJ, Herring K, Brookes CL, Ahmed I, Marshall A, Grieve R, Churn M, Spooner D, Latief TN, Agrawal RK, Brunt AM, Stevens A, Goodman A, Canney P, Bishop J, Ritchie D, Dunn J, Poole CJ, Rea DW; SECRAB Investigators. Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial. Radiother Oncol. 2020 Jan;142:52-61. Epub 2019 Nov 27. [https://doi.org/10.1016/j.radonc.2019.10.014 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31785830/ PubMed] NCT00003893
 
−
 
 
−
==CMFT {{#subobject:acff18|Regimen=1}}==
 
−
 
 
−
CMFT: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>T</u>'''amoxifen
 
−
===Regimen variant #1, 600/40/600 x 9, 30 x 12 mo {{#subobject:9f63d1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S0140-6736(98)09201-0 Overgaard et al. 1999 (DBCG 82C)]
 
−
|rowspan=2|1982-1990
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior DFS<sup>1</sup>
 
−
|-
 
−
|2. [[#Tamoxifen_.26_RT_99|Tamoxifen & RT]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for this arm versus tamoxifen monotherapy is based on the 2013 update.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 9: 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 1 to 9: 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 1 to 9: 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 30 mg PO once per day
 
−
 
 
−
'''28-day cycle for 13 cycles'''
 
−
 
 
−
===Regimen variant #2, 780/80/1000 x 6, 20 x 2 yr {{#subobject:9ajbd1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2736822/ Park et al. 2009 (Taiho 91023033)]
 
−
|1996-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#UFT_.26_Tamoxifen_88|UFT & Tamoxifen]]
 
−
| style="background-color:#eeee01" |Non-inferior RFS60
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 6: 65 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 1 to 6: 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] as follows:
 
−
**Cycles 1 to 6: 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
 
 
−
'''28-day cycle for 26 cycles'''
 
−
 
 
−
===Regimen variant #3, 840/50/800/40 x 12 {{#subobject:9f63d1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://www.surgjournal.com/article/0039-6060(80)90244-5 Hubay et al. 1980]
 
−
|rowspan=2|NR
 
−
|rowspan=2 style="background-color:#1a9851" |Randomized (E-RT-esc)
 
−
|1. [[#CMF|CMF]]
 
−
| style="background-color:#91cf60" |Seems to have superior RFS
 
−
|-
 
−
|2. [[#CMFT_.26_BCG_99|CMFT & BCG]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of RFS/OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 30 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO twice per day
 
−
 
 
−
'''28-day cycle for 12 cycles'''
 
−
 
 
−
===References===
 
−
# Hubay CA, Pearson OH, Marshall JS, Rhodes RS, Debanne SM, Mansour EG, Hermann RE, Jones JC, Flynn WJ, Eckert C, McGuire WL. Antiestrogen, cytotoxic chemotherapy, and bacillus Calmette-Guerin vaccination in stage II breast cancer: a preliminary report. Surgery. 1980 May;87(5):494-501. [https://www.surgjournal.com/article/0039-6060(80)90244-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7368100 PubMed]
 
−
## '''Update:''' Hubay CA, Pearson OH, Marshall JS, Rhodes RS, DeBanne SM, Rosenblatt J, Mansour EG, Hermann RE, Jones JC, Flynn WJ, Eckert C, McGuire WL. Adjuvant chemotherapy, antiestrogen therapy and immunotherapy for stage II breast cancer: 45-month follow-up of a prospective, randomized clinical trial. Cancer. 1980 Dec 15;46(12 Suppl):2805-8. [https://doi.org/10.1002/1097-0142(19801215)46:12%2B%3C2805::AID-CNCR2820461413%3E3.0.CO;2-H link to original article] [https://pubmed.ncbi.nlm.nih.gov/7004624 PubMed]
 
−
# '''NCIC-CTG MA.4:''' Pritchard KI, Paterson AH, Paul NA, Zee B, Fine S, Pater J; National Cancer Institute of Canada Clinical Trials Group. Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. J Clin Oncol. 1996 Oct;14(10):2731-7. [https://doi.org/10.1200/JCO.1996.14.10.2731 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8874334 PubMed]
 
−
## '''Update:''' Pritchard KI, Paterson AH, Fine S, Paul NA, Zee B, Shepherd LE, Abu-Zahra H, Ragaz J, Knowling M, Levine MN, Verma S, Perrault D, Walde PL, Bramwell VH, Poljicak M, Boyd N, Warr D, Norris BD, Bowman D, Armitage GR, Weizel H, Buckman RA; NCIC-CTG. Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1997 Jun;15(6):2302-11. [https://doi.org/10.1200/JCO.1997.15.6.2302 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9196144 PubMed]
 
−
# '''NSABP B-20:''' Fisher B, Dignam J, Wolmark N, DeCillis A, Emir B, Wickerham DL, Bryant J, Dimitrov NV, Abramson N, Atkins JN, Shibata H, Deschenes L, Margolese RG. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1997 Nov 19;89(22):1673-82. [https://academic.oup.com/jnci/article/89/22/1673/2526493 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9390536 PubMed]
 
−
## '''Pooled update:''' Fisher B, Jeong JH, Bryant J, Anderson S, Dignam J, Fisher ER, Wolmark N; National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet. 2004 Sep 4-10;364(9437):858-68. [https://doi.org/10.1016/S0140-6736(04)16981-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/15351193 PubMed]
 
−
## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://doi.org/10.1200/JCO.2006.06.9054 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16921044 PubMed]
 
−
# '''DBCG 82C:''' Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, Kamby C, Kjaer M, Gadeberg CC, Rasmussen BB, Blichert-Toft M, Mouridsen HT. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999 May 15;353(9165):1641-8. [https://doi.org/10.1016/S0140-6736(98)09201-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10335782 PubMed]
 
−
## '''Update:''' Ejlertsen B, Jensen MB, Elversang J, Rasmussen BB, Andersson M, Andersen J, Nielsen DL, Cold S, Mouridsen HT. One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer. Eur J Cancer. 2013 Sep;49(14):2986-94. Epub 2013 Jun 8. [https://www.ejcancer.com/article/S0959-8049(13)00383-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23756360 PubMed]
 
−
# '''Taiho 91023033:''' Park Y, Okamura K, Mitsuyama S, Saito T, Koh J, Kyono S, Higaki K, Ogita M, Asaga T, Inaji H, Komichi H, Kohno N, Yamazaki K, Tanaka F, Ito T, Nishikawa H, Osaki A, Koyama H, Suzuki T. Uracil-tegafur and tamoxifen vs cyclophosphamide, methotrexate, fluorouracil, and tamoxifen in post-operative adjuvant therapy for stage I, II, or IIIA lymph node-positive breast cancer: a comparative study. Br J Cancer. 2009 Aug 18;101(4):598-604. Epub 2009 Jul 28. Erratum in: Br J Cancer. 2009 Sep 15;101(6):1031. [https://doi.org/10.1038/sj.bjc.6605218 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2736822/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19638976/ PubMed] NCT00152178
 
−
 
 
−
==Dose-dense Cyclophosphamide monotherapy {{#subobject:2ba5c2|Regimen=1}}==
 
−
 
 
−
ddC: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>C</u>'''yclophosphamide
 
−
===Regimen variant #1, 600 mg/m<sup>2</sup> {{#subobject:6f231e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.09.081 Citron et al. 2003 (CALGB 9741)]
 
−
|1997-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
−
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[#Paclitaxel monotherapy.2C_dose-dense_.28q2wk.29_2|ddT]] x 4
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg (rounded to either 300 or 480 mcg) SC once per day on days 3 to 10
 
−
**Note: Citron et al. 2003 says the schedule was "filgrastim days 3 to 10 of each cycle (a total of seven doses)," so it is unclear whether 7 or 8 doses was actually used).
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
 
 
−
===Regimen variant #2, 800 mg/m<sup>2</sup> {{#subobject:822b10|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.karger.com/Article/Abstract/86987 Kahan et al. 2005]
 
−
|2000-2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[#Paclitaxel monotherapy.2C_dose-dense_.28q2wk.29_2|ddT]] x 4
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]]
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
 
 
−
===References===
 
−
# '''CALGB 9741:''' Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. [https://doi.org/10.1200/jco.2003.09.081 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12668651 PubMed] NCT00003088
 
−
# Kahan Z, Uhercsak G, Hajnal-Papp R, Boda K, Thurzo L. Dose-dense sequential adriamycin-paclitaxel-cyclophosphamide chemotherapy is well tolerated and safe in high-risk early breast cancer. Oncology. 2005;68(4-6):446-53. Epub 2005 Jul 13. [http://www.karger.com/Article/Abstract/86987 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16020975 PubMed]
 
−
## '''Update:''' Kelemen G, Uhercsák G, Ormándi K, Eller J, Thurzó L, Kahán Z. Long-term efficiency and toxicity of adjuvant dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy in high-risk breast cancer. Oncology. 2010;78(3-4):271-3. Epub 2010 Jun 7. [https://doi.org/10.1159/000315734 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20523088 PubMed]
 
−
 
 
−
==Cyclophosphamide & Docetaxel (TC) {{#subobject:faf430|Regimen=1}}==
 
−
 
 
−
TC: '''<u>T</u>'''axotere (Docetaxel) & '''<u>C</u>'''yclophosphamide
 
−
<br>DC: '''<u>D</u>'''ocetaxel & '''<u>C</u>'''yclophosphamide
 
−
===Regimen variant #1, 4 cycles {{#subobject:e9499f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.06.5391 Jones et al. 2006 (USOR 9735)]
 
−
|1997-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ Blum et al. 2017 (USOR 06-090)]
 
−
|2007-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TAC_.28Docetaxel.29_2|TAC]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior IDFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ Blum et al. 2017 (NSABP-46-I/USOR 07132)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TAC_.28Docetaxel.29_2|TAC]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior IDFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ Blum et al. 2017 (NSABP B-49)]
 
−
|2012-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TAC_.28Docetaxel.29_2|TAC]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior IDFS
 
−
|-
 
−
|}
 
−
''Note: Blum et al. 2017 is a pooled analysis of three RCTs, some of which had arms other than TAC and TC. Refer to the paper for further details.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*All cycles given with [[Filgrastim (Neupogen)]] support
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===Regimen variant #2, 6 cycles {{#subobject:d321b7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.18.00028 Nitz et al. 2019 (WSG PlanB)]
 
−
|2000-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#EC-D_2|EC-D]]
 
−
| style="background-color:#eeee01" |Non-inferior DFS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdw274 Mavroudis et al. 2016 (HORG CT/07.17)]
 
−
|2007-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#Dose-dense_FEC-D|ddFEC-D]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS36
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.72.3494 Ejlertsen et al. 2017 (DBCG 07-READ)]
 
−
|2008-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#EC-D_2|EC-D]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS<br>DFS60: 88.3% vs 87.9%<br>(HR 1.00, 95% CI 0.78-1.28)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7007289/ Fehrenbacher et al. 2019 (NSABP B-47)]
 
−
|2011-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#AC-TH_99|AC-TH]]<br>2. [[#Dose-dense_AC-TH_99|ddAC-TH]]<br>3. [[#TCH_99|TCH]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS
 
−
|-
 
−
|}
 
−
====Biomarker eligibility criteria====
 
−
*DBCG 07-READ: TOP2A normal as determined by FISH
 
−
*NSABP B-47: HER2 IHC of 1+ or 2+ with FISH ratio less than 2 or HER2 gene copy number less than 4
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===References===
 
−
# '''USOR 9735:''' Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006 Dec 1;24(34):5381-7. Erratum in: J Clin Oncol. 2007 May 1;25(13):1819. [https://doi.org/10.1200/jco.2006.06.5391 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17135639 PubMed]
 
−
## '''Update:''' Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology research trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83. Epub 2009 Feb 9. [https://doi.org/10.1200/jco.2008.18.4028 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19204201 PubMed]
 
−
# '''HORG CT/07.17:''' Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; HORG. Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2016 Oct;27(10):1873-8. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw274 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27502729 PubMed] NCT01985724
 
−
# '''USOR 06-090:''' Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, Robert NJ, Hopkins JO, O'Shaughnessy JA, Dang CT, Gómez HL, Fehrenbacher L, Vukelja SJ, Lyss AP, Paul D, Brufsky AM, Jeong JH, Colangelo LH, Swain SM, Mamounas EP, Jones SE, Wolmark N. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-2655. Epub 2017 Apr 11. [https://doi.org/10.1200/JCO.2016.71.4147 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28398846 PubMed] NCT00493870
 
−
# '''NSABP-46-I/USOR 07132:''' Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, Robert NJ, Hopkins JO, O'Shaughnessy JA, Dang CT, Gómez HL, Fehrenbacher L, Vukelja SJ, Lyss AP, Paul D, Brufsky AM, Jeong JH, Colangelo LH, Swain SM, Mamounas EP, Jones SE, Wolmark N. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-2655. Epub 2017 Apr 11. [https://doi.org/10.1200/JCO.2016.71.4147 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28398846 PubMed] NCT00887536
 
−
# '''NSABP B-49:''' Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, Robert NJ, Hopkins JO, O'Shaughnessy JA, Dang CT, Gómez HL, Fehrenbacher L, Vukelja SJ, Lyss AP, Paul D, Brufsky AM, Jeong JH, Colangelo LH, Swain SM, Mamounas EP, Jones SE, Wolmark N. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-2655. Epub 2017 Apr 11. [https://doi.org/10.1200/JCO.2016.71.4147 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28398846 PubMed] NCT01547741
 
−
# '''DBCG 07-READ:''' Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Højris I, Ewertz M, Balslev E, Danø H, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol. 2017 Aug 10;35(23):2639-2646. Epub 2017 Jun 29. [https://doi.org/10.1200/JCO.2017.72.3494 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28661759 PubMed] NCT00689156
 
−
# '''WSG PlanB:''' Nitz U, Gluz O, Clemens M, Malter W, Reimer T, Nuding B, Aktas B, Stefek A, Pollmanns A, Lorenz-Salehi F, Uleer C, Krabisch P, Kuemmel S, Liedtke C, Shak S, Wuerstlein R, Christgen M, Kates RE, Kreipe HH, Harbeck N; West German Study Group. West German Study PlanB trial: adjuvant four cycles of epirubicin and cyclophosphamide plus docetaxel versus six cycles of docetaxel and cyclophosphamide in HER2-negative early breast cancer. J Clin Oncol. 2019 Apr 1;37(10):799-808. Epub 2019 Feb 20. [https://doi.org/10.1200/JCO.18.00028 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30785826 PubMed] NCT01049425
 
−
# '''NSABP B-47:''' Fehrenbacher L, Cecchini RS, Geyer CE Jr, Rastogi P, Costantino JP, Atkins JN, Crown JP, Polikoff J, Boileau JF, Provencher L, Stokoe C, Moore TD, Robidoux A, Flynn PJ, Borges VF, Albain KS, Swain SM, Paik S, Mamounas EP, Wolmark N. NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+ or 2. J Clin Oncol. 2020 Feb 10;38(5):444-453. Epub 2019 Dec 10. [https://doi.org/10.1200/jco.19.01455 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7007289/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31821109/ PubMed] NCT01275677
 
−
#'''ASTER 70s:''' NCT01564056
 
−
 
 
−
==Cyclophosphamide & Doxorubicin (AC) {{#subobject:77b0fd|Regimen=1}}==
 
−
 
 
−
AC: '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide
 
−
<br>CA: '''<u>C</u>'''yclophosphamide and '''<u>A</u>'''driamycin (Doxorubicin)
 
−
===Regimen variant #1, 54/1200 x 6 {{#subobject:8f5df7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2006.07.0847 Linden et al. 2007 (INT-0137)]
 
−
|1994-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#A-C_99|A-C]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Doxorubicin (Adriamycin)]] 54 mg/m<sup>2</sup> IV once on day 1
+
*[[Carboplatin (Paraplatin)]] AUC 5 or 6 IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV once on day 1
+
*[[Paclitaxel (Taxol)]] 175 or 200 mg/m<sup>2</sup> IV once on day 1
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #2, 60/600 x 4 {{#subobject:ac3513|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1997.15.7.2483 Fisher et al. 1997 (NSABP B-18)]
 
−
|1988-1993
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29|AC]]; neoadjuvant
 
−
| style="background-color:#d73027" |Inferior resectability
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1997.15.5.1858 Fisher et al. 1997 (NSABP B-22)]
 
−
|1989-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]]; intensified<br> 2. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]]; intensified & increased
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2001.19.4.931 Fisher et al. 2001 (NSABP B-23)]
 
−
|1991-1998
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CMF|CMF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1023/a:1011118004629 Içli et al. 2001]
 
−
|1992-1996
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.02.063 Henderson et al. 2003 (INT 0148/CALGB 9344)]
 
−
|1994-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]]; high-dose<br> 2. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]]; very high dose
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.10.517 Mamounas et al. 2005 (NSABP B-28)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#AC-T_2|AC-T]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.06.5391 Jones et al. 2006 (USOR 9735)]
 
−
|1997-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Docetaxel_.28TC.29|TC]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654376/ Goldstein et al. 2008 (ECOG E2197)]
 
−
|1998-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Doxorubicin_.28AT.29_99|AT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/fullarticle/200883 Brain et al. 2005 (RAPP-01)]
 
−
|1999-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Doxorubicin_.28AT.29_99|AT]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082436/ Muss et al. 2009 (CALGB 49907)]
 
−
|2001-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_monotherapy|Capecitabine]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2018.79.2028 Miller et al. 2018 (ECOG E5103)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#ECOG_E5103|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#ECOG_E5103|See link]]
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*Most protocols: [[Surgery#Breast_cancer_surgery|Surgery]]
 
−
*INT 0148/CALGB 9344: [[Surgery#Breast_cancer_surgery|Surgery]], within 84 days
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
====Subsequent treatment====
 
−
*NSABP B-23: [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 y versus [[Breast_cancer_-_null_regimens#Placebo|placebo]]
 
−
*Içli et al. 2001: EP x 2 versus [[Breast_cancer_-_null_regimens#Observation|no further treatment]]
 
−
*INT 0148/CALGB 9344: [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|q3wk T (Taxol)]] x 4 versus [[Breast_cancer_-_null_regimens#Observation|no further therapy]]
 
−
*ECOG E5103: [[#Paclitaxel_monotherapy.2C_weekly|weekly T (Taxol)]] x 12
 
−
 
 
−
===Regimen variant #3, 80/600 x 4 {{#subobject:42ada7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2006.08.9383 Moore et al. 2007 (SWOG S9623)]
 
−
|1996-2001
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 80 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*STAMP-I or [[Breast_cancer_-_historical#CTCb.2C_then_auto_HSCT|STAMP-V, with auto HSCT]]
 
−
 
 
−
===References===
 
−
# '''NSABP B-22:''' Fisher B, Anderson S, Wickerham DL, DeCillis A, Dimitrov N, Mamounas E, Wolmark N, Pugh R, Atkins JN, Meyers FJ, Abramson N, Wolter J, Bornstein RS, Levy L, Romond EH, Caggiano V, Grimaldi M, Jochimsen P, Deckers P. Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22. J Clin Oncol. 1997 May;15(5):1858-69. [https://doi.org/10.1200/JCO.1997.15.5.1858 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9164196 PubMed]
 
−
## '''Pooled update:''' Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. [https://doi.org/10.1200/JCO.2004.01.042 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15452182 PubMed]
 
−
# '''NSABP B-18:''' Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB Jr, Fisher ER, Wickerham DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NV. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997 Jul;15(7):2483-93. [https://doi.org/10.1200/JCO.1997.15.7.2483 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9215816 PubMed]
 
−
## '''Update:''' Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. [https://doi.org/10.1200/JCO.1998.16.8.2672 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9704717 PubMed]
 
−
## '''Update:''' Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst. 2001;(30):96-102. [https://doi.org/10.1093/oxfordjournals.jncimonographs.a003469 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11773300 PubMed]
 
−
## '''Pooled update:''' Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. [https://doi.org/10.1200/JCO.2004.01.042 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15452182 PubMed]
 
−
## '''Pooled update:''' Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. [https://doi.org/10.1200/JCO.2007.15.0235 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18258986 PubMed]
 
−
# '''NSABP B-23:''' Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. [https://doi.org/10.1200/jco.2001.19.4.931 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11181655 PubMed]
 
−
# Içli F, Akbulut H, Dinçol D, Onur H, Demirkazik A, Cam R, Cay F, Demirci S, Uner A, Erekul S. A randomized trial of four cycles of adjuvant AC (adriamycin + cyclophosphamide) +/- two cycles of EP (etoposide + cisplatin) in node positive patients with breast cancer. Ann Oncol. 2001 Jul;12(7):1011-3. [https://doi.org/10.1023/a:1011118004629 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11521785 PubMed]
 
−
# '''INT 0148/CALGB 9344:''' Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. [https://doi.org/10.1200/jco.2003.02.063 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12637460 PubMed]
 
−
<!-- Presented in abstract form at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003; interim results were presented at the 2000 NIH Consensus Development Conference, Bethesda, MD, November 1-3, 2000. -->
 
−
# '''NSABP B-28:''' Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. [https://doi.org/10.1200/jco.2005.10.517 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15897552 PubMed]
 
−
# '''RAPP-01:''' Brain EG, Bachelot T, Serin D, Kirscher S, Graic Y, Eymard JC, Extra JM, Combe M, Fourme E, Noguès C, Rouëssé J; RAPP-01 Trial Investigators. Life-threatening sepsis associated with adjuvant doxorubicin plus docetaxel for intermediate-risk breast cancer. JAMA. 2005 May 18;293(19):2367-71. [https://jamanetwork.com/journals/jama/fullarticle/200883 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15900007 PubMed]
 
−
# '''USOR 9735:''' Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006 Dec 1;24(34):5381-7. Erratum in: J Clin Oncol. 2007 May 1;25(13):1819. [https://doi.org/10.1200/jco.2006.06.5391 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17135639 PubMed]
 
−
## '''Update:''' Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology research trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83. Epub 2009 Feb 9. [https://doi.org/10.1200/jco.2008.18.4028 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19204201 PubMed]
 
−
# '''INT-0137:''' Linden HM, Haskell CM, Green SJ, Osborne CK, Sledge GW Jr, Shapiro CL, Ingle JN, Lew D, Hutchins LF, Livingston RB, Martino S. Sequenced compared with simultaneous anthracycline and cyclophosphamide in high-risk stage I and II breast cancer: final analysis from INT-0137 (S9313). J Clin Oncol. 2007 Feb 20;25(6):656-61. [https://doi.org/10.1200/JCO.2006.07.0847 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17308269 PubMed]
 
−
# '''SWOG S9623:''' Moore HC, Green SJ, Gralow JR, Bearman SI, Lew D, Barlow WE, Hudis C, Wolff AC, Ingle JN, Chew HK, Elias AD, Livingston RB, Martino S; [[Study_Groups#SWOG|SWOG]]. Intensive dose-dense compared with high-dose adjuvant chemotherapy for high-risk operable breast cancer: Southwest Oncology Group/Intergroup study 9623. J Clin Oncol. 2007 May 1;25(13):1677-82. Epub 2007 Apr 2. [https://doi.org/10.1200/JCO.2006.08.9383 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17404368 PubMed] NCT00002772
 
−
# '''ECOG E2197:''' Goldstein LJ, O'Neill A, Sparano JA, Perez EA, Shulman LN, Martino S, Davidson NE. Concurrent doxorubicin plus docetaxel is not more effective than concurrent doxorubicin plus cyclophosphamide in operable breast cancer with 0 to 3 positive axillary nodes: North American Breast Cancer Intergroup Trial E 2197. J Clin Oncol. 2008 Sep 1;26(25):4092-9. Epub 2008 Aug 4. [https://doi.org/10.1200/JCO.2008.16.7841 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654376/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18678836 PubMed] NCT00003519
 
−
# '''CALGB 49907:''' Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Becker HP, Kartcheske PA, Wheeler JD, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Magrinat G, Parker BA, Hart RD, Grenier D, Norton L, Hudis CA, Winer EP; CALGB. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009 May 14;360(20):2055-65. Erratum in: N Engl J Med. 2009 Oct 22;361(17):1714. Magrinat, Gutav [corrected to Magrinat, Gustav]. [https://doi.org/10.1056/NEJMoa0810266 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082436/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19439741 PubMed] NCT00024102
 
−
# '''ECOG E5103:''' Miller KD, O'Neill A, Gradishar W, Hobday TJ, Goldstein LJ, Mayer IA, Bloom S, Brufsky AM, Tevaarwerk AJ, Sparano JA, Le-Lindqwister NA, Hendricks CB, Northfelt DW, Dang CT, Sledge GW Jr. Double-blind phase III trial of adjuvant chemotherapy with and without bevacizumab in patients with lymph node-positive and high-risk lymph node-negative breast cancer (E5103). J Clin Oncol. 2018 Sep 1;36(25):2621-2629. Epub 2018 Jul 24. [https://doi.org/10.1200/JCO.2018.79.2028 link to original article] '''refers to ECOG E1199 protocol''' [https://pubmed.ncbi.nlm.nih.gov/30040523 PubMed] NCT00433511
 
−
#'''ASTER 70s:''' NCT01564056
 
−
 
 
−
==Dose-dense Cyclophosphamide & Doxorubicin (ddAC) {{#subobject:b52056|Regimen=1}}==
 
−
 
 
−
ddAC: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide
 
−
===Regimen variant #1, 60/600 x 4 {{#subobject:cdafd0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="3" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ Shulman et al. 2012 (CALGB 40101)]
 
−
| rowspan="3" |2002-2008
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 6
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|2. [[#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|ddT]] x 4
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|3. [[#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|ddT]] x 6
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.02.8621 Burstein et al. 2005]
 
−
|2003-2004
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ Swain et al. 2013 (NSABP B-38)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#NSABP_B-38|See link]]
 
−
|[[Complex_multipart_regimens#NSABP_B-38|See link]]
 
−
|-
 
−
|}
 
−
''Note: CALGB 40101 originally specified 21-day cycles but was amended to 14-day cycles after results of CALGB 9741 were available.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*(varies depending on reference):
 
−
*Burstein et al. 2005:
 
−
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2, given 24 hours after chemotherapy
 
−
*Burstein et al. 2005, for patients with Hb 10 to 12 g/dL:
 
−
**[[Darbepoetin alfa (Aranesp)]] 200 mcg SC once on day 1
 
−
***See Burstein et al. 2005 for additional dose adjustments
 
−
*CALGB 40101: one of the following:
 
−
**[[Filgrastim (Neupogen)]] 5 mcg/kg (rounded to 300 mcg or 480 mcg, whichever is closer) SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
 
−
**[[Sargramostim (Leukine)]] 250 to 500 mcg/m<sup>2</sup> SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
 
−
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once, given 24 to 36 hours after chemotherapy
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
 
 
−
====Subsequent treatment====
 
−
*Burstein et al. 2005: [[#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|ddT (Taxol)]] x 4
 
−
*NSABP B-38: [[#Paclitaxel monotherapy.2C_dose-dense_.28q2wk.29_2|ddT (Taxol)]] x 4 versus [[#ddPG_99|ddPG]] x 4
 
−
 
 
−
===Regimen variant #2, 60/600 x 6 {{#subobject:b6b259|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268253/ Budd et al. 2014 (SWOG S0221)]
 
−
|2003-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]]; continuous
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(18)30982-1 van Rossum et al. 2018 (MATADOR)]
 
−
|2004-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#TAC_.28Docetaxel.29_2|TAC]]
 
−
| style="background-color:#ffffbf" |Did not meet secondary endpoints of RFS/OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
 
−
 
 
−
'''14-day cycle for 6 cycles'''
 
−
====Subsequent treatment====
 
−
*SWOG S0221: [[#Paclitaxel monotherapy.2C_dose-dense_.28q2wk.29_2|Bi-weekly paclitaxel]] versus [[#Paclitaxel_monotherapy.2C_weekly|weekly paclitaxel]]
 
−
===References===
 
−
# Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. [https://doi.org/10.1200/jco.2005.02.8621 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16293865 PubMed]
 
−
# '''CALGB 40101:''' Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. [https://doi.org/10.1200/jco.2011.40.6405 link to original article] '''contains dosing details in manuscript''' [https://ascopubs.org/doi/suppl/10.1200/jco.2011.40.6405/suppl_file/Protocol.pdf link to study protocol PDF] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22826271 PubMed] NCT00041119
 
−
## '''Update:''' Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. [https://doi.org/10.1200/jco.2013.53.7142 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105484/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24934787 PubMed]
 
−
# '''NSABP B-38:''' Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. Epub 2013 Aug 12. [https://doi.org/10.1200/JCO.2012.48.1275 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23940225 PubMed] NCT00093795
 
−
# '''SWOG S0221:''' Budd GT, Barlow WE, Moore HC, Hobday TJ, Stewart JA, Isaacs C, Salim M, Cho JK, Rinn KJ, Albain KS, Chew HK, Burton GV, Moore TD, Srkalovic G, McGregor BA, Flaherty LE, Livingston RB, Lew DL, Gralow JR, Hortobagyi GN. SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. J Clin Oncol. 2015 Jan 1;33(1):58-64. Epub 2014 Nov 24. [https://doi.org/10.1200/JCO.2014.56.3296 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268253/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25422488 PubMed] NCT00070564
 
−
# '''ECOG E5103:''' Miller KD, O'Neill A, Gradishar W, Hobday TJ, Goldstein LJ, Mayer IA, Bloom S, Brufsky AM, Tevaarwerk AJ, Sparano JA, Le-Lindqwister NA, Hendricks CB, Northfelt DW, Dang CT, Sledge GW Jr. Double-blind phase III trial of adjuvant chemotherapy with and without bevacizumab in patients with lymph node-positive and high-risk lymph node-negative breast cancer (E5103). J Clin Oncol. 2018 Sep 1;36(25):2621-2629. Epub 2018 Jul 24. [https://doi.org/10.1200/JCO.2018.79.2028 link to original article] '''refers to ECOG E1199 protocol''' [https://pubmed.ncbi.nlm.nih.gov/30040523 PubMed] NCT00433511
 
−
# '''MATADOR:''' van Rossum AGJ, Kok M, van Werkhoven E, Opdam M, Mandjes IAM, van Leeuwen-Stok AE, van Tinteren H, Imholz ALT, Portielje JEA, Bos MMEM, van Bochove A, Wesseling J, Rutgers EJ, Linn SC, Oosterkamp HM; MATADOR Trialists' Group. Adjuvant dose-dense doxorubicin-cyclophosphamide versus docetaxel-doxorubicin-cyclophosphamide for high-risk breast cancer: first results of the randomised MATADOR trial (BOOG 2004-04). Eur J Cancer. 2018 Oct;102:40-48. [https://www.ejcancer.com/article/S0959-8049(18)30982-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30125761 PubMed] ISRCTN61893718
 
−
 
 
−
==Cyclophosphamide & Epirubicin (EC) {{#subobject:8d8dbe|Regimen=1}}==
 
−
 
 
−
EC: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide
 
−
===Regimen variant #1, 60/500 x 8 {{#subobject:50bd25|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2001.19.12.3103 Piccart et al. 2001 (Belgian trial)]
 
−
|rowspan=2|1988-1996
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#CMF|CMF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|2. [[#Cyclophosphamide_.26_Epirubicin_.28EC.29|EC]]; high-dose
 
−
| style="background-color:#fc8d59" |Seems to have inferior EFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #2, 75/600 x 4 {{#subobject:2e39fe|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdh016 Pico et al. 2004 (GEICAM 9401)]
 
−
|1995-2000
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#ECT_.28Tamoxifen.29_88|ECT (Tamoxifen)]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Tamoxifen_monotherapy_88|Tamoxifen]]
 
−
 
 
−
===Regimen variant #3, 90/600 x 4 {{#subobject:22ed5f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.07.026 Zander et al. 2004]
 
−
|1993-2000
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361407/ Kümmel et al. 2006]
 
−
|1996-2000
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#K.C3.BCmmel_et_al._2006|See link]]
 
−
| style="background-color:#fee08b" |[[Complex_multipart_regimens#K.C3.BCmmel_et_al._2006|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*Zander et al. 2004: [[#CMF|CMF]] x 3 versus [[#Cyclophosphamide.2C_Mitoxantrone.2C_Thiotepa.2C_then_auto_HSCT_88|cyclophosphamide, mitoxantrone, thiotepa with auto HSCT]]
 
−
 
 
−
===Regimen variant #4, 100/830 x 8 {{#subobject:aead26|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2001.19.12.3103 Piccart et al. 2001 (Belgian trial)]
 
−
|rowspan=2|1988-1996
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#CMF|CMF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|2. [[#Cyclophosphamide_.26_Epirubicin_.28EC.29|EC]]; moderate-dose
 
−
| style="background-color:#91cf60" |Seems to have superior EFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 830 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #5, 120/600 x 4 (high-dose) {{#subobject:24260d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2003.03.034 Papaldo et al. 2003]
 
−
|1991-1994
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Epirubicin_.28EC.29_.26_Lonidamine_77|EC & Lonidamine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362268/ Vici et al. 2011 (GOIM 9902)]
 
−
|1999-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#D-EC_99|D-EC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*Papaldo et al. 2003: [[Surgery#Breast_cancer_surgery|Surgery]]
 
−
*GOIM 9902: [[Surgery#Breast_cancer_surgery|Surgery]] versus [[Surgery#Breast_cancer_surgery|Surgery]], then [[#Docetaxel_monotherapy|D]] x 4
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 120 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===References===
 
−
# '''Belgian trial:''' Piccart MJ, Di Leo A, Beauduin M, Vindevoghel A, Michel J, Focan C, Tagnon A, Ries F, Gobert P, Finet C, Closon-Dejardin MT, Dufrane JP, Kerger J, Liebens F, Beauvois S, Bartholomeus S, Dolci S, Lobelle JP, Paesmans M, Nogaret JM. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001 Jun 15;19(12):3103-10. [https://doi.org/10.1200/jco.2001.19.12.3103 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11408507 PubMed]
 
−
## '''Update:''' de Azambuja E, Paesmans M, Beauduin M, Vindevoghel A, Cornez N, Finet C, Ries F, Closon-Dejardin MT, Kerger J, Gobert P, Focan C, Tagnon A, Dolci S, Nogaret JM, di Leo A, Piccart-Gebhart MJ. Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node-positive breast cancer: 15-year efficacy results of the Belgian multicentre study. J Clin Oncol. 2009 Feb 10;27(5):720-5. Epub 2008 Dec 22. [https://doi.org/10.1200/JCO.2008.17.2155 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19103732 PubMed]
 
−
# Papaldo P, Lopez M, Cortesi E, Cammilluzzi E, Antimi M, Terzoli E, Lepidini G, Vici P, Barone C, Ferretti G, Di Cosimo S, Nistico C, Carlini P, Conti F, Di Lauro L, Botti C, Vitucci C, Fabi A, Giannarelli D, Marolla P. Addition of either lonidamine or granulocyte colony-stimulating factor does not improve survival in early breast cancer patients treated with high-dose epirubicin and cyclophosphamide. J Clin Oncol. 2003 Sep 15;21(18):3462-8. [https://doi.org/10.1200/JCO.2003.03.034 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12972521 PubMed]
 
−
# '''GEICAM 9401:''' Pico C, Martin M, Jara C, Barnadas A, Pelegri A, Balil A, Camps C, Frau A, Rodriguez-Lescure A, Lopez-Vega JM, De La Haba J, Tres A, Alvarez I, Alba E, Arcusa A, Oltra A, Batista N, Checa T, Perez-Carrion R, Curto J; GEICAM. Epirubicin-cyclophosphamide adjuvant chemotherapy plus tamoxifen administered concurrently versus sequentially: randomized phase III trial in postmenopausal node-positive breast cancer patients: a GEICAM 9401 study. Ann Oncol. 2004 Jan;15(1):79-87. [https://doi.org/10.1093/annonc/mdh016 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14679124 PubMed]
 
−
# Zander AR, Kröger N, Schmoor C, Krüger W, Möbus V, Frickhofen N, Metzner B, Schultze W, Berdel WE, Koenigsmann M, Thiel E, Wandt H, Possinger K, Trümper L, Kreienberg R, Carstensen M, Schmidt EH, Jänicke F, Schumacher M, Jonat W. High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: first results of a randomized trial. J Clin Oncol. 2004 Jun 15;22(12):2273-83. Epub 2004 Apr 26. [https://doi.org/10.1200/JCO.2004.07.026 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15111618 PubMed]
 
−
# Kümmel S, Krocker J, Kohls A, Breitbach GP, Morack G, Budner M, Blohmer JU, Elling D. Randomised trial: survival benefit and safety of adjuvant dose-dense chemotherapy for node-positive breast cancer. Br J Cancer. 2006 May 8;94(9):1237-44. [https://www.nature.com/articles/6603085 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361407/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16622463 PubMed]
 
−
## '''Update:''' Reinisch M, Gluz O, Ataseven B, Blohmer JU, Budner M, Dittmer-Grabowski C, Kohls A, Krocker J, Kümmel A, Hagemann F, Rüland A, Traut A, Kümmel S. Updated Survival Analysis after a Median Follow-up of 12 Years of an Anthracycline-Containing Adjuvant Prospective Multicentre, Randomised Phase III Trial on Dose-Dense Chemotherapy in Primary Node-Positive, High-Risk Breast Cancer Patients. Breast Care (Basel). 2019 Jun;14(3):159-164. Epub 2018 Sep 5. [https://doi.org/10.1159/000491792 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6600045/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31316314/ PubMed]
 
−
# '''GOIM 9902:''' Vici P, Brandi M, Giotta F, Foggi P, Schittulli F, Di Lauro L, Gebbia N, Massidda B, Filippelli G, Giannarelli D, Di Benedetto A, Mottolese M, Colucci G, Lopez M. A multicenter phase III prospective randomized trial of high-dose epirubicin in combination with cyclophosphamide (EC) versus docetaxel followed by EC in node-positive breast cancer: GOIM (Gruppo Oncologico Italia Meridionale) 9902 study. Ann Oncol. 2012 May;23(5):1121-9. Epub 2011 Sep 28. [https://doi.org/10.1093/annonc/mdr412 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362268/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21965475 PubMed]
 
−
# '''GIM2:''' Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. Epub 2015 Mar 2. [https://doi.org/10.1016/s0140-6736(14)62048-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25740286 PubMed] NCT00433420
 
−
 
 
−
==Dose-dense Cyclophosphamide & Epirubicin (ddEC) {{#subobject:824585|Regimen=1}}==
 
−
 
 
−
ddEC: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide
 
−
===Regimen variant #1, 90/600 {{#subobject:aa6006|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(05)67784-7 Nitz et al. 2005 (WSG AM-01)]
 
−
|1995-2002
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Epirubicin_.28EC.29|EC]], then [[Breast_cancer_-_historical#ECT.2C_then_auto_HSCT|ECT with auto HSCT]] x 2
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(14)62048-1 Del Mastro et al. 2015 (GIM2)]
 
−
|2003-2006
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#GIM2|See link]]
 
−
|[[Complex_multipart_regimens#GIM2|See link]]
 
−
|-
 
−
|}
 
−
''Note: a mid-protocol amendment of GIM2 suggested giving the pegilgrastim at least 72 h after chemotherapy.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*WSG AM-01: [[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 5 to 12
 
−
*GIM2: [[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*WSG AM-01: [[#ddCMF_88|ddCMF]] x 3
 
−
*GIM2: [[#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|Dose-dense Paclitaxel]]
 
−
 
 
−
===Regimen variant #2, 120/830 {{#subobject:bc9489|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799234/ Burnell et al. 2009 (NCIC-CTG MA.21)]
 
−
|2000-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#NCIC_CTG_MA.21|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#NCIC_CTG_MA.21|See link]]
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 120 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 830 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 2 to 13
 
−
*[[Epoetin alfa (Procrit)]] 40,000 units SC once per day on days 1 & 8
 
−
 
 
−
'''14-day cycle for 6 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T (Taxol)]] x 4
 
−
 
 
−
===References===
 
−
# '''WSG AM-01:''' Nitz UA, Mohrmann S, Fischer J, Lindemann W, Berdel WE, Jackisch C, Werner C, Ziske C, Kirchner H, Metzner B, Souchon R, Ruffert U, Schütt G, Pollmanns A, Schmoll HJ, Middecke C, Baltzer J, Schrader I, Wiebringhaus H, Ko Y, Rösel S, Schwenzer T, Wernet P, Hinke A, Bender HG, Frick M; West German Study Group. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial. Lancet. 2005 Dec 3;366(9501):1935-44. Erratum in: Lancet. 2006 Mar 4;367(9512):730. [https://doi.org/10.1016/S0140-6736(05)67784-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16325695 PubMed]
 
−
# '''NCIC-CTG MA.21:''' Burnell M, Levine MN, Chapman JA, Bramwell V, Gelmon K, Walley B, Vandenberg T, Chalchal H, Albain KS, Perez EA, Rugo H, Pritchard K, O'Brien P, Shepherd LE. Cyclophosphamide, epirubicin, and fluorouracil versus dose-dense epirubicin and cyclophosphamide followed by paclitaxel versus doxorubicin and cyclophosphamide followed by paclitaxel in node-positive or high-risk node-negative breast cancer. J Clin Oncol. 2010 Jan 1;28(1):77-82. Epub 2009 Nov 9. [https://doi.org/10.1200/JCO.2009.22.1077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799234/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19901117 PubMed] NCT00014222
 
−
# '''GIM2:''' Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. Epub 2015 Mar 2. [https://doi.org/10.1016/s0140-6736(14)62048-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25740286 PubMed] NCT00433420
 
−
 
 
−
==Docetaxel monotherapy {{#subobject:45c144|Regimen=1}}==
 
−
 
 
−
D: '''<u>D</u>'''ocetaxel
 
−
<br>T: '''<u>T</u>'''axotere (Docetaxel)
 
−
<br>dT: '''<u>d</u>'''oce'''<u>T</u>'''axel
 
−
 
 
−
===Regimen variant #3, 100 mg/m<sup>2</sup> q3wk x 3 {{#subobject:bfeef2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa053028 Joensuu et al. 2006 (FinHer)]
 
−
|2000-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Vinorelbine_monotherapy|Vinorelbine]]
 
−
| style="background-color:#1a9850" |Superior RFS <br>(HR 0.58, 95% CI 0.40-0.85)
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in FinHer without HER2/neu amplification were only randomized to this or the [[#Vinorelbine_monotherapy|vinorelbine arm]].''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
 
'''21-day cycle for 3 cycles'''
 
'''21-day cycle for 3 cycles'''
−
 
+
</div>
−
===Regimen variant #4, 100 mg/m<sup>2</sup> q3wk x 4 {{#subobject:199d79|Variant=1}}===
+
<div class="toccolours" style="background-color:#cbd5e7">
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2003.12.005 Bear et al. 2003 (NSABP B-27)]
 
−
|1995-2000
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#NSABP_B-27|See link]]
 
−
|[[Complex_multipart_regimens#NSABP_B-27|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*NSABP B-27: Neoadjuvant [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29|AC]] x 4, then [[Surgery#Breast_cancer_surgery|surgery]]
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
===References===
 
−
# '''NSABP B-27:''' Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N; National Surgical Adjuvant Breast and Bowel Project. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003 Nov 15;21(22):4165-74. Epub 2003 Oct 14. [https://doi.org/10.1200/JCO.2003.12.005 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14559892 PubMed] NCT00002707
 
−
## '''Update:''' Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006 May 1;24(13):2019-27. Epub 2006 Apr 10. [https://doi.org/10.1200/JCO.2005.04.1665 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16606972 PubMed]
 
−
## '''Pooled update:''' Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. [https://doi.org/10.1200/JCO.2007.15.0235 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18258986 PubMed]
 
−
<!-- no pre-pub disclosed -->
 
−
# '''FinHer:''' Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. [https://doi.org/10.1056/NEJMoa053028 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16495393 PubMed] ISRCTN76560285
 
−
## '''Update:''' Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. [https://doi.org/10.1200/JCO.2008.21.4577 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19884557 PubMed]
 
−
# '''NSAS BC-02:''' Watanabe T, Kuranami M, Inoue K, Masuda N, Aogi K, Ohno S, Iwata H, Mukai H, Uemura Y, Ohashi Y. Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study. Cancer. 2017 Mar 1;123(5):759-768. Epub 2017 Jan 12. [https://doi.org/10.1002/cncr.30421 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28081304 PubMed]
 
−
 
 
−
==Dose-dense Docetaxel monotherapy {{#subobject:08ad0f|Regimen=1}}==
 
−
 
 
−
ddT: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>T</u>'''axotere (Docetaxel)
 
−
<br>ddD: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>D</u>'''ocetaxel
 
−
===Regimen {{#subobject:a00f8d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-014-3202-5 Saloustros et al. 2014 (HORG CT/04.22)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|ddT (Taxol)]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[#Dose-dense_FEC|ddFEC]] x 4
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|Filgrastim]] or [[:Category:Granulocyte_colony-stimulating_factors|Pegfilgrastim]] support (drug/dose/schedule not specified)
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
 
 
−
===References===
 
−
# '''HORG CT/04.22:''' Saloustros E, Malamos N, Boukovinas I, Kakolyris S, Kouroussis C, Athanasiadis A, Ziras N, Kentepozidis N, Makrantonakis P, Polyzos A, Christophyllakis C, Georgoulias V, Mavroudis D. Dose-dense paclitaxel versus docetaxel following FEC as adjuvant chemotherapy in axillary node-positive early breast cancer: a multicenter randomized study of the Hellenic Oncology Research Group (HORG). Breast Cancer Res Treat. 2014 Dec;148(3):591-7. Epub 2014 Nov 16. [https://doi.org/10.1007/s10549-014-3202-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25399229 PubMed] NCT00431080
 
−
# '''HORG CT/07.17:''' Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; Hellenic Oncology Research Group. Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2016 Oct;27(10):1873-8. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw274 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27502729 PubMed] NCT01985724
 
−
 
 
−
==Doxorubicin monotherapy {{#subobject:cc64af|Regimen=1}}==
 
−
 
 
−
A: '''<u>A</u>'''driamycin (Doxorubicin)
 
−
===Regimen {{#subobject:a45aaa|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1991.9.12.2134 Buzzoni et al. 1991 (Milan trial)]
 
−
|1982-1987
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#Milan_trial|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#Milan_trial|See link]]
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/96/14/1076/2520847 Leonard et al. 2004]
 
−
|1995-1999
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2008.19.2567 Gianni et al. 2009 (ECTO)]
 
−
|1996-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#ECTO|See link]]
 
−
| style="background-color:#fc8d59" |[[Complex_multipart_regimens#ECTO|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*Milan trial & Leonard et al. 2004: [[#CMF|CMF]] x 8
 
−
*ECTO: [[#CMF|CMF]] x 4
 
−
 
 
−
===References===
 
−
# '''Milan trial:''' Buzzoni R, Bonadonna G, Valagussa P, Zambetti M. Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil in the treatment of resectable breast cancer with more than three positive axillary nodes. J Clin Oncol. 1991 Dec;9(12):2134-40. [https://doi.org/10.1200/JCO.1991.9.12.2134 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1960555 PubMed]
 
−
## '''Update:''' Bonadonna G, Zambetti M, Valagussa P. Sequential or alternating doxorubicin and CMF regimens in breast cancer with more than three positive nodes: ten-year results. JAMA. 1995 Feb 15;273(7):542-7. [https://jamanetwork.com/journals/jama/fullarticle/387001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7837388 PubMed]
 
−
# Leonard RC, Lind M, Twelves C, Coleman R, van Belle S, Wilson C, Ledermann J, Kennedy I, Barrett-Lee P, Perren T, Verrill M, Cameron D, Foster E, Yellowlees A, Crown J; Anglo-Celtic Cooperative Oncology Group. Conventional adjuvant chemotherapy versus single-cycle, autograft-supported, high-dose, late-intensification chemotherapy in high-risk breast cancer patients: a randomized trial. J Natl Cancer Inst. 2004 Jul 21;96(14):1076-83. [https://academic.oup.com/jnci/article/96/14/1076/2520847 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15265969 PubMed]
 
−
# '''ECTO:''' Gianni L, Baselga J, Eiermann W, Porta VG, Semiglazov V, Lluch A, Zambetti M, Sabadell D, Raab G, Cussac AL, Bozhok A, Martinez-Agulló A, Greco M, Byakhov M, Lopez JJ, Mansutti M, Valagussa P, Bonadonna G. Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol. 2009 May 20;27(15):2474-81. Epub 2009 Mar 30. [https://doi.org/10.1200/JCO.2008.19.2567 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19332727 PubMed] NCT00003013
 
−
 
 
−
==Dose-dense Doxorubicin monotherapy {{#subobject:c9fa7d|Regimen=1}}==
 
−
 
 
−
ddA: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin)
 
−
===Regimen {{#subobject:90fd28|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.09.081 Citron et al. 2003 (CALGB 9741)]
 
−
|1997-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
−
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
−
|-
 
−
|[http://www.karger.com/Article/Abstract/86987 Kahan et al. 2005]
 
−
|2000-2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]]
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Paclitaxel monotherapy.2C_dose-dense_.28q2wk.29_2|ddT]]
 
−
 
 
−
===References===
 
−
# '''CALGB 9741:''' Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. [https://doi.org/10.1200/jco.2003.09.081 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12668651 PubMed] NCT00003088
 
−
# Kahan Z, Uhercsak G, Hajnal-Papp R, Boda K, Thurzo L. Dose-dense sequential adriamycin-paclitaxel-cyclophosphamide chemotherapy is well tolerated and safe in high-risk early breast cancer. Oncology. 2005;68(4-6):446-53. Epub 2005 Jul 13. [http://www.karger.com/Article/Abstract/86987 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16020975 PubMed]
 
−
## '''Update:''' Kelemen G, Uhercsák G, Ormándi K, Eller J, Thurzó L, Kahán Z. Long-term efficiency and toxicity of adjuvant dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy in high-risk breast cancer. Oncology. 2010;78(3-4):271-3. Epub 2010 Jun 7. [https://doi.org/10.1159/000315734 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20523088 PubMed]
 
−
 
 
−
==Doxorubicin & Paclitaxel (AT) {{#subobject:0ed69b|Regimen=1}}==
 
−
 
 
−
AT: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>T</u>'''axol (Paclitaxel)
 
−
===Regimen {{#subobject:61e706|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2008.19.2567 Gianni et al. 2009 (ECTO)]
 
−
|1996-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#ECTO|See link]]
 
−
| style="background-color:#91cf60" |[[Complex_multipart_regimens#ECTO|See link]]
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#CMF|CMF]] x 4
 
−
===References===
 
−
# '''ECTO:''' Gianni L, Baselga J, Eiermann W, Porta VG, Semiglazov V, Lluch A, Zambetti M, Sabadell D, Raab G, Cussac AL, Bozhok A, Martinez-Agulló A, Greco M, Byakhov M, Lopez JJ, Mansutti M, Valagussa P, Bonadonna G. Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol. 2009 May 20;27(15):2474-81. Epub 2009 Mar 30. [https://doi.org/10.1200/JCO.2008.19.2567 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19332727 PubMed] NCT00003013
 
−
 
 
−
==Epirubicin & Paclitaxel (EP) {{#subobject:332a92|Regimen=1}}==
 
−
 
 
−
EP: '''<u>E</u>'''pirubicin & '''<u>P</u>'''aclitaxel
 
−
===Regimen {{#subobject:4824ee|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdm539 Fountzilas et al. 2007 (HE 10/00)]
 
−
|2000-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Dose-dense_E-P_99|ddE, then ddP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 83 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Paclitaxel (Taxol)]] 187 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#ddCMF_88|ddCMF]] x 3
 
−
 
 
−
===References===
 
−
# '''HE 10/00:''' Fountzilas G, Dafni U, Gogas H, Linardou H, Kalofonos HP, Briasoulis E, Pectasides D, Samantas E, Bafaloukos D, Stathopoulos GP, Karina M, Papadimitriou C, Skarlos D, Pisanidis N, Papakostas P, Markopoulos C, Tzorakoeleftherakis E, Dimitrakakis K, Makrantonakis P, Xiros N, Polichronis A, Varthalitis I, Karanikiotis C, Dimopoulos AM; Hellenic Cooperative Oncology Group. Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00. Ann Oncol. 2008 May;19(5):853-60. Epub 2007 Nov 27. [https://doi.org/10.1093/annonc/mdm539 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18042835 PubMed]
 
−
## '''Update:''' Gogas H, Dafni U, Karina M, Papadimitriou C, Batistatou A, Bobos M, Kalofonos HP, Eleftheraki AG, Timotheadou E, Bafaloukos D, Christodoulou C, Markopoulos C, Briasoulis E, Papakostas P, Samantas E, Kosmidis P, Stathopoulos GP, Karanikiotis C, Pectasides D, Dimopoulos MA, Fountzilas G. Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial. Breast Cancer Res Treat. 2012 Apr;132(2):609-19. Epub 2011 Dec 21. [https://doi.org/10.1007/s10549-011-1913-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22187126 PubMed]
 
−
 
 
−
==iddEnPC {{#subobject:28hgzn|Regimen=1}}==
 
−
 
 
−
iddEnPC: '''<u>i</u>'''ntense '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>E</u>'''pirubicin, '''<u>n</u>'''ab-'''<u>P</u>'''aclitaxel, '''<u>C</u>'''yclophosphamide
 
−
===Protocol {{#subobject:ca3ug1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.ejca.2021.07.033 Möbus et al. 2021 (GAIN-2)]
 
−
|2012-2017
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#dtEC-dtD_99|dtEC-dtD]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of iDFS
 
−
|-
 
−
|}
 
−
''Note: growth factor support is not specifically mentioned in the manuscript. The details below for pegfilgrastim are based on the GAIN trial of iddEPC.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, part 1====
 
−
*[[Epirubicin (Ellence)]] 150 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2 or 4
 
−
 
 
−
'''14-day cycle for 3 cycles, then:'''
 
−
====Chemotherapy, part 2====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 330 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2 or 4
 
−
 
 
−
'''14-day cycle for 3 cycles, then:'''
 
−
====Chemotherapy, part 3====
 
−
*[[Cyclophosphamide (Cytoxan)]] 2000 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2 or 4
 
−
 
 
−
'''14-day cycle for 3 cycles'''
 
−
===References===
 
−
#'''GAIN-2:''' Möbus V, Lück HJ, Ladda E, Klare P, Schmidt M, Schneeweiss A, Grischke EM, Wachsmann G, Forstbauer H, Untch M, Marmé F, Blohmer JU, Jackisch C, Huober J, Stickeler E, Reinisch M, Link T, Sinn BV, Janni W, Denkert C, Furlanetto J, Engels K, Solbach C, Schmatloch S, Rey J, Burchardi N, Loibl S; GBG and AGO-B. Phase III randomised trial comparing intense dose-dense chemotherapy to tailored dose-dense chemotherapy in high-risk early breast cancer (GAIN-2). Eur J Cancer. 2021 Oct;156:138-148. Epub 2021 Aug 24. [https://doi.org/10.1016/j.ejca.2021.07.033 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34450552/ PubMed] NCT01690702
 
−
 
 
−
==iddEPC {{#subobject:28ad40|Regimen=1}}==
 
−
 
 
−
iddEPC: '''<u>i</u>'''ntense '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>E</u>'''pirubicin, '''<u>P</u>'''aclitaxel, '''<u>C</u>'''yclophosphamide
 
−
<br>IDD-ETC: '''<u>I</u>'''ntense '''<u>D</u>'''ose-'''<u>D</u>'''ense '''<u>E</u>'''pirubicin, '''<u>T</u>'''axol (Paclitaxel), '''<u>C</u>'''yclophosphamide
 
−
===Protocol {{#subobject:ca391d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2009.24.7643 Möbus et al. 2010 (AGO-iddEPC)]
 
−
|1998-2003
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#EC-T_2|EC-T]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS120: 69% vs 59%<br>(HR 0.72, 95% CI 0.60-0.87)
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdx203 Möbus et al. 2017 (GAIN)]
 
−
|2004-2008
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Dose-dense_Cyclophosphamide_.26_Epibicin_.28ddEC.29|ddEC]], then [[#Capecitabine_.26_Paclitaxel_.28XP.29_99|XP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for AGO-iddEPC is based on the 2018 update.''<br>
 
−
''Note: this dosing of cyclophosphamide was after a mid-protocol amendment of GAIN.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy, part 1====
 
−
*[[Epirubicin (Ellence)]] 150 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2 or 4
 
−
 
 
−
'''14-day cycle for 3 cycles, then:'''
 
−
====Chemotherapy, part 2====
 
−
*[[Paclitaxel (Taxol)]] 225 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2 or 4
 
−
 
 
−
'''14-day cycle for 3 cycles, then:'''
 
−
====Chemotherapy, part 3====
 
−
*[[Cyclophosphamide (Cytoxan)]] 2000 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2 or 4
 
−
 
 
−
'''14-day cycle for 3 cycles'''
 
−
===References===
 
−
# '''AGO-iddEPC:''' Moebus V, Jackisch C, Lueck HJ, du Bois A, Thomssen C, Kurbacher C, Kuhn W, Nitz U, Schneeweiss A, Huober J, Harbeck N, von Minckwitz G, Runnebaum IB, Hinke A, Kreienberg R, Konecny GE, Untch M. Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer: mature results of an AGO phase III study. J Clin Oncol. 2010 Jun 10;28(17):2874-80. Epub 2010 May 10. [https://doi.org/10.1200/JCO.2009.24.7643 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20458045 PubMed]
 
−
## '''Update:''' Möbus V, Jackisch C, Lück HJ, du Bois A, Thomssen C, Kuhn W, Nitz U, Schneeweiss A, Huober J, Harbeck N, von Minckwitz G, Runnebaum IB, Hinke A, Konecny GE, Untch M, Kurbacher C; AGO Breast Study Group (AGO-B). Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial. Ann Oncol. 2018 Jan 1;29(1):178-185. [https://doi.org/10.1093/annonc/mdx690 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29069370 PubMed]
 
−
# '''GAIN:''' Möbus V, von Minckwitz G, Jackisch C, Lück HJ, Schneeweiss A, Tesch H, Elling D, Harbeck N, Conrad B, Fehm T, Huober J, Müller V, Bauerfeind I, du Bois A, Loibl S, Nekljudova V, Untch M, Thomssen C; German Breast Group; AGO Breast Study Group (AGO-B); NOGGO. German Adjuvant Intergroup Node-positive Study (GAIN): a phase III trial comparing two dose-dense regimens (iddEPC versus ddEC-PwX) in high-risk early breast cancer patients. Ann Oncol. 2017 Aug 1;28(8):1803-1810. [https://doi.org/10.1093/annonc/mdx203 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28459941 PubMed] NCT00196872
 
−
 
 
−
==Epirubicin monotherapy {{#subobject:fda4d3|Regimen=1}}==
 
−
 
 
−
E: '''<u>E</u>'''pirubicin
 
−
===Regimen variant #1, 75 mg/m<sup>2</sup> {{#subobject:b83fae|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1990.8.8.1310 Boccardo et al. 1990 (GROCTA-1)]
 
−
|1983-1987
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#GROCTA-1|See link]]
 
−
|[[Complex_multipart_regimens#GROCTA-1|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[#CMF|CMF]] x 6
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 y versus [[Breast_cancer_-_null_regimens#Observation|no further treatment]]
 
−
 
 
−
===Regimen variant #4, 100 mg/m<sup>2</sup> x 6, split doses {{#subobject:f04ubx|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.32.7254 Coombes et al. 2011 (DEVA)]
 
−
|1997-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#E-D|E-D]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
===References===
 
−
# '''GROCTA-1:''' Boccardo F, Rubagotti A, Bruzzi P, Cappellini M, Isola G, Nenci I, Piffanelli A, Scanni A, Sismondi P, Santi L, Genta F, Saccani F, Sassi M, Malacarne P, Donati D, Farris A, Castagnetta L, Di Carlo A, Traina A, Galletto L, Smerieri F, Buzzi F; Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group. Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. J Clin Oncol. 1990 Aug;8(8):1310-20. [https://doi.org/10.1200/JCO.1990.8.8.1310 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2199618 PubMed]
 
−
## '''Update:''' Boccardo F, Guglielmini P, Parodi A, Rubagotti A. Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen receptor-positive breast cancer patients: very late results of the 'gruppo di ricerca per la chemio-ormonoterapia adiuvante (GROCTA)' 01-Trial in early breast cancer. Breast Cancer Res Treat. 2011 Apr;126(3):653-61. Epub 2011 Feb 24. [https://doi.org/10.1007/s10549-011-1405-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21347647 PubMed]
 
−
<!-- Presented at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL. -->
 
−
# '''DEVA:''' Coombes RC, Bliss JM, Espie M, Erdkamp F, Wals J, Tres A, Marty M, Coleman RE, Tubiana-Mathieu N, den Boer MO, Wardley A, Kilburn LS, Cooper D, Thomas MW, Reise JA, Wilkinson K, Hupperets P. Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with  node-positive breast cancer. J Clin Oncol. 2011 Aug 20;29(24):3247-54. Epub 2011 Jul 18. [https://doi.org/10.1200/JCO.2010.32.7254 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21768453 PubMed] ISRCTN89772270
 
−
 
 
−
==Dose-dense Epirubicin monotherapy {{#subobject:fda8g3|Regimen=1}}==
 
−
 
 
−
ddE: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>E</u>'''pirubicin
 
−
===Regimen variant #1, 3 cycles {{#subobject:9134b2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223601/ Fountzilas et al. 2014 (HE10/05)]
 
−
|2005-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 110 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''14-day cycle for 3 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#CMF_2|CMF]]; intensified
 
−
 
 
−
===Regimen variant #2, 4 cycles {{#subobject:91cbc2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdi366 Fountzilas et al. 2005 (HE 10/97)]
 
−
|1997-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#HE_10.2F97|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#HE_10.2F97|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 110 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 3 to 10
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#CMF_2|CMF]]; intensified
 
−
 
 
−
===References===
 
−
# '''HE 10/97:''' Fountzilas G, Skarlos D, Dafni U, Gogas H, Briasoulis E, Pectasides D, Papadimitriou C, Markopoulos C, Polychronis A, Kalofonos HP, Siafaka V, Kosmidis P, Timotheadou E, Tsavdaridis D, Bafaloukos D, Papakostas P, Razis E, Makrantonakis P, Aravantinos G, Christodoulou C, Dimopoulos AM; Hellenic Cooperative Oncology Group. Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol. 2005 Nov;16(11):1762-71. Epub 2005 Sep 7. [https://doi.org/10.1093/annonc/mdi366 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16148021 PubMed]
 
−
# '''HE10/05:''' Fountzilas G, Dafni U, Papadimitriou C, Timotheadou E, Gogas H, Eleftheraki AG, Xanthakis I, Christodoulou C, Koutras A, Papandreou CN, Papakostas P, Miliaras S, Markopoulos C, Dimitrakakis C, Korantzopoulos P, Karanikiotis C, Bafaloukos D, Kosmidis P, Samantas E, Varthalitis I, Pavlidis N, Pectasides D, Dimopoulos MA. Dose-dense sequential adjuvant chemotherapy followed, as indicated, by trastuzumab for one year in patients with early breast cancer: first report at 5-year median follow-up of a Hellenic Cooperative Oncology Group randomized phase III trial. BMC Cancer. 2014 Jul 15;14:515. [https://doi.org/10.1186/1471-2407-14-515 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223601/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25026897 PubMed]
 
−
 
 
−
==FAC {{#subobject:1e6621|Regimen=1}}==
 
−
 
 
−
FAC: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
 
−
<br>CAF: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil
 
−
===Regimen variant #1, 500/40/500 x 6 {{#subobject:041nc6|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1349-7006.2007.00639.x Tokuda et al. 2007 (JCOG 9208)]
 
−
|1993-1999
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Cyclophosphamide_.26_Thiotepa.2C_then_auto_HSCT_88|Cyclophosphamide & Thiotepa, then auto HSCT]], then [[#Tamoxifen_monotherapy_88|tamoxifen]] versus [[#Tamoxifen_monotherapy_88|tamoxifen]]
 
−
 
 
−
===Regimen variant #2, 500/50/500 x 4 {{#subobject:04f8a6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.46.9841 Martín et al. 2013 (GEICAM 2003-02)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#GEICAM.2F2003-02|See link]]
 
−
|style="background-color:#91cf60" |[[Complex_multipart_regimens#GEICAM.2F2003-02|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Paclitaxel_monotherapy.2C_weekly|wP]] x 8
 
−
 
 
−
===Regimen variant #3, 500/50/500 x 6 {{#subobject:63e780|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdg260 Martin et al. 2003 (GEICAM 8701)]
 
−
|1987-1991
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CMF|CMF]]
 
−
| style="background-color:#d9ef8b" |Might have superior DFS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa043681 Martin et al. 2005 (BCIRG 001)]
 
−
|1997-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TAC_.28Docetaxel.29_2|TAC]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa0910320 Martín et al. 2010 (GEICAM 9805)]
 
−
|1999-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TAC_.28Docetaxel.29_2|TAC]]
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.46.9841 Martín et al. 2013 (GEICAM 2003-02)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FAC_2|FAC]], then [[#Paclitaxel_monotherapy.2C_weekly|wP]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.01371 Delaloge et al. 2020 (MINDACT)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_99|TX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
''Infusion times per Martin et al. 2005 (BCIRG 001).''
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV over 15 minutes once on day 1, '''given second'''
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV over 15 minutes once on day 1, '''given first'''
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV over 1 to 5 minutes once on day 1, '''given third'''
 
−
**A HemOnc.org user reached out to us and said their institutional practice is to infuse cyclophosphamide over 20 to 30 minutes to decrease the likelihood of head and sinus pain.
 
−
 
 
−
====Supportive therapy====
 
−
*If patients had febrile neutropenia or infection: [[Ciprofloxacin (Cipro)]] 500 mg PO twice per day on days 5 to 14
 
−
*If patients had febrile neutropenia, one of the following:
 
−
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 4 to 11
 
−
**[[Lenograstim (Granocyte)]] 150 mcg/m<sup>2</sup> SC once per day on days 4 to 11
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #4, 800/40/400 x 6 {{#subobject:23cb8b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1056/NEJM199405053301801 Wood et al. 1994 (CALGB 8541)]
 
−
|rowspan=2|1985-NR
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#FAC_2|FAC]]; 600/30/300 x 4
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|2. [[#FAC_2|FAC]]; 1200/60/600 x 4
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #5, 800/40/400 until max doxorubicin {{#subobject:53e7a0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19840201)53:3%3C384::AID-CNCR2820530303%3E3.0.CO;2-G Buzdar et al. 1984]
 
−
|1977-1980
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FAC_.26_BCG_99|FAC + BCG]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles until cumulative doxorubicin dose of 300 mg/m<sup>2</sup> reached.'''
 
−
====Subsequent treatment====
 
−
*After reaching cumulative maximum doxorubicin, patients would go on to receive maintenance CMF. This is now obsolete.
 
−
 
 
−
===Regimen variant #6, 1000/50/500 x 8 {{#subobject:a3523e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/92/3/225/2965047 Hortobagyi et al. 2000]
 
−
|1990-1997
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 4
 
−
*[[Doxorubicin (Adriamycin)]] 16.7 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 50 mg/m<sup>2</sup>)
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#CEP.2C_then_auto_HSCT_99|CEP with auto HSCT]] versus [[Breast_cancer_-_null_regimens#Observation|no further treatment]]
 
−
 
 
−
===Regimen variant #7, 1000/60/1400 x 6 {{#subobject:f18a6a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.05.551 Davidson et al. 2005 (ECOG E5188)]
 
−
|1989-1994
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.08.071 Hutchins et al. 2005 (INT-0102)]
 
−
|1989-1993
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CMF|CMF]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140679/ Albain et al. 2009 (SWOG-8814)]
 
−
|1989-1995
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#SWOG-8814|See link]]
 
−
| style="background-color:#d9ef8b" |[[Complex_multipart_regimens#SWOG-8814|See link]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa030684 Tallman et al. 2003 (INT-0121)]
 
−
|1991-1998
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
====Subsequent treatment====
 
−
*INT-0121: [[#Cyclophosphamide_.26_Thiotepa.2C_then_auto_HSCT_88|Cyclophosphamide & thiotepa, then auto HSCT]] versus [[Breast_cancer_-_null_regimens#Observation|no further chemotherapy]]
 
−
*ECOG E5188: [[#Goserelin_monotherapy_99|Goserelin]] x 5 y versus [[Breast_cancer,_ER-positive#Goserelin_.26_Tamoxifen|Goserelin & Tamoxifen]] x 5 y versus [[Breast_cancer_-_null_regimens#Observation|no further treatment]]
 
−
*SWOG-8814: [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 y
 
−
 
 
−
===Regimen variant #8, 1200/60/600 x 4 {{#subobject:7953f3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1056/NEJM199405053301801 Wood et al. 1994 (CALGB 8541)]
 
−
|rowspan=2|1985-NR
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#FAC_2|FAC]]; 600/30/300 x 4
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|2. [[#FAC_2|FAC]]; 800/40/400 x 6
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycle for 4 cycles'''
 
−
 
 
−
===Regimen variant #9, 1200/60/600 x 6 {{#subobject:7abnf3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.01371 Delaloge et al. 2020 (MINDACT)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_99|TX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
===References===
 
−
# Buzdar AU, Blumenschein GR, Smith TL, Powell KC, Hortobagyi GN, Yap HY, Schell FC, Barnes BC, Ames FC, Martin RG, Hersh EM. Adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide, with or without Bacillus Calmette-Guérin and with or without irradiation in operable breast cancer: a prospective randomized trial. Cancer. 1984 Feb 1;53(3):384-9. [https://doi.org/10.1002/1097-0142(19840201)53:3%3C384::AID-CNCR2820530303%3E3.0.CO;2-G link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6362814 PubMed]
 
−
## '''Update:''' Buzdar AU, Kau SW, Smith TL, Hortobagyi GN. Ten-year results of FAC adjuvant chemotherapy trial in breast cancer. Am J Clin Oncol. 1989 Apr;12(2):123-8. [https://doi.org/10.1097/00000421-198904000-00007 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2705401 PubMed]
 
−
# '''CALGB 8541:''' Wood WC, Budman DR, Korzun AH, Cooper MR, Younger J, Hart RD, Moore A, Ellerton JA, Norton L, Ferree CR, Colangelo Ballow A, Frei E, Henderson IC. Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med. 1994 May 5;330(18):1253-9. Erratum in: N Engl J Med 1994 Jul 14;331(2):139. [https://doi.org/10.1056/NEJM199405053301801 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8080512 PubMed]
 
−
## '''Subgroup analysis:''' Muss HB, Thor AD, Berry DA, Kute T, Liu ET, Koerner F, Cirrincione CT, Budman DR, Wood WC, Barcos M, Henderson IC. c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med. 1994 May 5;330(18):1260-6. Erratum in: N Engl J Med 1994 Jul 21;331(3):211. [https://doi.org/10.1056/NEJM199405053301802 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7908410 PubMed]
 
−
# Hortobagyi GN, Buzdar AU, Theriault RL, Valero V, Frye D, Booser DJ, Holmes FA, Giralt S, Khouri I, Andersson B, Gajewski JL, Rondon G, Smith TL, Singletary SE, Ames FC, Sneige N, Strom EA, McNeese MD, Deisseroth AB, Champlin RE. Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma. J Natl Cancer Inst. 2000 Feb 2;92(3):225-33. [https://academic.oup.com/jnci/article/92/3/225/2965047 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10655439 PubMed]
 
−
# '''GEICAM 8701:''' Martin M, Villar A, Sole-Calvo A, Gonzalez R, Massuti B, Lizon J, Camps C, Carrato A, Casado A, Candel MT, Albanell J, Aranda J, Munarriz B, Campbell J, Diaz-Rubio E; GEICAM. Doxorubicin in combination with fluorouracil and cyclophosphamide (iv FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (iv CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group. Ann Oncol. 2003 Jun;14(6):833-42. [https://doi.org/10.1093/annonc/mdg260 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12796019 PubMed]
 
−
# '''INT-0121:''' Tallman MS, Gray R, Robert NJ, LeMaistre CF, Osborne CK, Vaughan WP, Gradishar WJ, Pisansky TM, Fetting J, Paietta E, Lazarus HM. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. N Engl J Med. 2003 Jul 3;349(1):17-26. [https://doi.org/10.1056/NEJMoa030684 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12840088 PubMed]
 
−
<!-- no pre-pub disclosed -->
 
−
# '''BCIRG 001:''' Martín M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, Guevin R, Howell A, Fornander T, Hainsworth J, Coleman R, Vinholes J, Modiano M, Pinter T, Tang SC, Colwell B, Prady C, Provencher L, Walde D, Rodriguez-Lescure A, Hugh J, Loret C, Rupin M, Blitz S, Jacobs P, Murawsky M, Riva A, Vogel C; Breast Cancer International Research Group. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13. [https://doi.org/10.1056/NEJMoa043681 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15930421 PubMed] NCT00688740
 
−
## '''Update:''' Mackey JR, Martín M, Pienkowski T, Rolski J, Guastalla JP, Sami A, Glaspy J, Juhos E, Wardley A, Fornander T, Hainsworth J, Coleman R, Modiano MR, Vinholes J, Pinter T, Rodríguez-Lescure A, Colwell B, Whitlock P, Provencher L, Laing K, Walde D, Price C, Hugh JC, Childs BH, Bassi K, Lindsay MA, Wilson V, Rupin M, Houé V, Vogel C; TRIO/BCIRG 001 investigators. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol. 2013 Jan;14(1):72-80. Epub 2012 Dec 12. [https://doi.org/10.1016/S1470-2045(12)70525-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23246022 PubMed]
 
−
# '''ECOG E5188:''' Davidson NE, O'Neill AM, Vukov AM, Osborne CK, Martino S, White DR, Abeloff MD. Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188). J Clin Oncol. 2005 Sep 1;23(25):5973-82. Epub 2005 Aug 8. [https://doi.org/10.1200/JCO.2005.05.551 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16087950 PubMed]
 
−
# '''INT-0102:''' Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of intergroup protocol INT-0102. J Clin Oncol. 2005 Nov 20;23(33):8313-21. [https://doi.org/10.1200/jco.2005.08.071 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16293862 PubMed]
 
−
# '''JCOG 9208:''' Tokuda Y, Tajima T, Narabayashi M, Takeyama K, Watanabe T, Fukutomi T, Chou T, Sano M, Igarashi T, Sasaki Y, Ogura M, Miura S, Okamoto S, Ogita M, Kasai M, Kobayashi T, Fukuda H, Takashima S, Tobinai K; Autologous Bone Marrow Transplantation Study Group; Breast Cancer Study Group of the Japan Clinical Oncology Group (JCOG). Phase III study to evaluate the use of high-dose chemotherapy as consolidation of treatment for high-risk postoperative breast cancer: Japan Clinical Oncology Group study, JCOG 9208. Cancer Sci. 2008 Jan;99(1):145-51. Epub 2007 Oct 25. [https://doi.org/10.1111/j.1349-7006.2007.00639.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17970786/ PubMed]
 
−
# '''SWOG-8814:''' Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, Cobau CD, Levine EG, Ingle JN, Pritchard KI, Lichter AS, Schneider DJ, Abeloff MD, Henderson IC, Muss HB, Green SJ, Lew D, Livingston RB, Martino S, Osborne CK; Breast Cancer Intergroup of North America. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Dec 19;374(9707):2055-2063. Epub 2009 Dec 10. [https://doi.org/10.1016/S0140-6736(09)61523-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140679/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20004966 PubMed] NCT00929591
 
−
<!-- no pre-pub disclosed -->
 
−
# '''GEICAM 9805:''' Martín M, Seguí MA, Antón A, Ruiz A, Ramos M, Adrover E, Aranda I, Rodríguez-Lescure A, Grosse R, Calvo L, Barnadas A, Isla D, Martinez del Prado P, Ruiz Borrego M, Zaluski J, Arcusa A, Muñoz M, López Vega JM, Mel JR, Munarriz B, Llorca C, Jara C, Alba E, Florián J, Li J, López García-Asenjo JA, Sáez A, Rios MJ, Almenar S, Peiró G, Lluch A; GEICAM. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med. 2010 Dec 2;363(23):2200-10. [https://doi.org/10.1056/NEJMoa0910320 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21121833 PubMed] NCT00121992
 
−
<!-- Presented in part at the 48th Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2012, Chicago, IL. -->
 
−
# '''GEICAM 2003-02:''' Martín M, Ruiz A, Ruiz Borrego M, Barnadas A, González S, Calvo L, Margelí Vila M, Antón A, Rodríguez-Lescure A, Seguí-Palmer MA, Muñoz-Mateu M, Dorca Ribugent J, López-Vega JM, Jara C, Espinosa E, Mendiola Fernández C, Andrés R, Ribelles N, Plazaola A, Sánchez-Rovira P, Salvador Bofill J, Crespo C, Carabantes FJ, Servitja S, Chacón JI, Rodríguez CA, Hernando B, Álvarez I, Carrasco E, Lluch A. Fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus FAC followed by weekly paclitaxel as adjuvant therapy for high-risk, node-negative breast cancer: results from the GEICAM/2003-02 study. J Clin Oncol. 2013 Jul 10;31(20):2593-9. Epub 2013 Jun 3. [https://doi.org/10.1200/jco.2012.46.9841 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23733779 PubMed] NCT00129389
 
−
# '''MINDACT:''' Delaloge S, Piccart M, Rutgers E, Litière S, van 't Veer LJ, van den Berkmortel F, Brain E, Dudek-Peric A, Gil-Gil M, Gomez P, Hilbers FS, Khalil Z, Knox S, Kuemmel S, Kunz G, Lesur A, Pierga JY, Ravdin P, Rubio IT, Saghatchian M, Smilde TJ, Thompson AM, Viale G, Zoppoli G, Vuylsteke P, Tryfonidis K, Poncet C, Bogaerts J, Cardoso F; MINDACT investigators and the TRANSBIG Consortium. Standard Anthracycline Based Versus Docetaxel-Capecitabine in Early High Clinical and/or Genomic Risk Breast Cancer in the EORTC 10041/BIG 3-04 MINDACT Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1186-1197. Epub 2020 Feb 21. [https://doi.org/10.1200/jco.19.01371 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/32083990 PubMed] NCT00433589
 
−
 
 
−
==FEC {{#subobject:3613b7|Regimen=1}}==
 
−
 
 
−
FEC: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide
 
−
<br>CEF: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>F</u>'''luorouracil
 
−
===Regimen variant #1, 500/50/500 x 6 ("FEC 50") {{#subobject:24ca82|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1988.6.4.679 Hurteloup 1988 (FESG)]
 
−
|1982-1984
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#FAC_2|FAC]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS50%
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.2003.04.148 Fumoleau et al. 2003 (FASG 01)]
 
−
|rowspan=2|1986-1990
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#FEC_2|FEC]]; FEC 50 x 3
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|2. [[#FEC_2|FEC]]; FEC 75 x 3
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS120
 
−
|-
 
−
|[http://www.jle.com/fr/revues/bdc/e-docs/epirubicin_based_chemotherapy_as_adjuvant_treatment_for_poor_prognosis_node_negative_breast_cancer_10_year_follow_up_results__272048/article.phtml Héry et al. 2006 (FASG 03)]
 
−
|1988-1994
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS120
 
−
|-
 
−
|[https://doi.org/10.1080/02841860510029987 Arriagada et al. 2005]
 
−
|1989-1996
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.3.602 Bonneterre 2001 (FASG 05)]
 
−
|1990-1993
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_2|FEC]]; FEC 100 x 6
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdl107 Roché et al. 2006 (FASG 06)]
 
−
|1990-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer,_ER-positive#Goserelin_.26_Tamoxifen_2|Goserelin & Tamoxifen]] x 3y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #2, 500/60/500 x 4 {{#subobject:ea8219|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0360-3016(05)02813-0 Rouëssé et al. 2006]
 
−
|1994-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FNC_.26_RT_99|FNC & RT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===Regimen variant #3, 500/100/500 x 4 ("FEC 100") {{#subobject:9cee26|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(17)30822-5 Kerbrat et al. 2017 (UCBG-0106)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#FEC_2|FEC]]; FEC 100 x 6
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|-
 
−
|}
 
−
''Note: this is an experimental arm that did not meet its primary endpoint; included here because it represents a de-escalation strategy.''
 
−
====Preceding treatment====
 
−
*UCBG-0106: [[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===Regimen variant #4, 500/100/500 x 6 ("FEC 100") {{#subobject:8382ec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.3.602 Bonneterre 2001 (FASG 05)]
 
−
|1990-1993
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#FEC_2|FEC]]; FEC 50 x 6
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359910/ Kerbrat et al. 2007 (FASG 09)]
 
−
|1993-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_.26_Vinorelbine_.28VE.29_99|VE]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.07.3916 Roché et al. 2006 (FNCLCC PACS 01)]
 
−
|1997-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC-D|FEC-D]]
 
−
| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(13)00898-8 Delbaldo et al. 2013 (Trial B2000)]
 
−
|2000-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC-P|FEC-P]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdu186 Nitz et al. 2014 (WSG-AGO EC-Doc)]
 
−
|2000-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#EC-D_2|EC-D]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2009.23.0946 Spielmann et al. 2009 (FNCLCC PACS 04)]
 
−
|2001-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Epirubicin_.28DE.29|ED]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS<sup>2</sup>
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(17)30822-5 Kerbrat et al. 2017 (UCBG-0106)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_2|FEC]]; FEC 100 x 4
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|-
 
−
|[https://doi.org/10.1007/s12032-013-0457-3 Sakr et al. 2013]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC-D|FEC-D]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.01371 Delaloge et al. 2020 (MINDACT)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_99|TX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for FNCLCC PACS 01 is based on the 2012 update.''<br>
 
−
''<sup>2</sup>Reported efficacy for FNCLCC PACS 04 is based on the 2019 update.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #5, 600/50/600 x 8 {{#subobject:85d304|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.1.35 Coombes et al. 1996]
 
−
|1984-1992
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CMF|CMF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of RFS/OS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(16)00156-8 Coombes et al. 2016 (HMFEC)]
 
−
|1992-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_2|FEC]]; FEC 75
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #6, 600/60/600 x 3 {{#subobject:e6b54b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa053028 Joensuu et al. 2006 (FinHer)]
 
−
|2000-2003
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[#Docetaxel_monotherapy|Docetaxel]] x 3 versus [[#Vinorelbine_monotherapy|Vinorelbine]] x 3
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
 
 
−
===Regimen variant #7, 600/60/600 x 4 {{#subobject:32aa4a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.22.4224 van der Hage et al. 2001 (EORTC 10902)]
 
−
|1991-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC|FEC]]; neoadjuvant
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===Regimen variant #8, 600/60/600 x 6 {{#subobject:d13a49|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/97/23/1724/2521486 Venturini et al. 2005 (MIG-1)]
 
−
|1992-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Dose-dense_FEC_99|Dose-dense FEC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdp602 Sirohi et al. 2010 (TRAFIC)]
 
−
|1995-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ECisF_99|ECisF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|[http://link.springer.com/article/10.1007/s10549-015-3655-1 del Mastro et al. 2016 (GONO-MIG5)]
 
−
|1996-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_.26_Paclitaxel_.28EP.29_2|EP]] x 4
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #9, 600/60/600 x 8 {{#subobject:695f44|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687939/ Ellis et al. 2009 (TACT)]
 
−
|2001-2003
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#FEC-D|FEC-D]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #10, 600/60/600 x 9 {{#subobject:cfbcd1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(07)00014-7 Ejlertsen et al. 2007 (DBCG 89D)]
 
−
|1990-1998
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#CMF|CMF]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 9 cycles'''
 
−
 
 
−
===Regimen variant #12, 600/90/600 x 6 {{#subobject:916209|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://jnci.oxfordjournals.org/content/100/11/805.long Martín et al. 2008 (GEICAM 9906)]
 
−
|1999-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC-P|FEC-P]]
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #13, 700/75/700 x 6 {{#subobject:31e320|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-009-0468-0 Polyzos et al. 2009]
 
−
|1995-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#D-EC|D-EC]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 700 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 700 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #14, 1000/50/500 x 6 {{#subobject:caf441|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.19.3929 Paradiso et al. 2001]
 
−
|1989-1994
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
===Regimen variant #15, 1000/120/740 x 6 ("Canadian CEF (IV)") {{#subobject:97uj50|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.01371 Delaloge et al. 2020 (MINDACT)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_99|TX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 370 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #16, 1000/120/1050 x 6 ("FEC 120"; "Canadian CEF") {{#subobject:978850|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1998.16.8.2651 Levine et al. 1998 (NCIC-CTG MA.5)]
 
−
|1989-1993
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#CMF|CMF]]
 
−
| style="background-color:#1a9850" |Superior RFS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdi166 Coombes et al. 2005 (ICCG HDT trial)]
 
−
|1993-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_2|FEC]] x 3, then HDT
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of RFS/EFS/OS
 
−
|-
 
−
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799234/ Burnell et al. 2009 (NCIC-CTG MA.21)]
 
−
|rowspan = 2|2000-2005
 
−
|rowspan = 2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#AC-T_2|AC-T]]
 
−
| style="background-color:#1a9850" |Superior RFS
 
−
|-
 
−
|2. [[#Dose-dense_Cyclophosphamide_.26_Epibicin_.28ddEC.29|ddEC]] x 6, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T (Taxol)]]; q3wk x 4
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984804/ Janni et al. 2016 (ADEBAR)]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#EC-D_2|EC-D]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.01371 Delaloge et al. 2020 (MINDACT)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_99|TX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #17, 1200/50/1200 x 6 {{#subobject:d46835|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.1.35 Coombes et al. 1996]
 
−
|1984-1992
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CMF|CMF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of RFS/OS
 
−
|-
 
−
|}
 
−
''Note: this is an experimental arm that did not meet its primary endpoint; however, based on a subgroup analysis, it became a preferred regimen.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
===References===
 
−
# '''FESG:''' Hurteloup P; French Epirubicin Study Group. A prospective randomized phase III trial comparing combination chemotherapy with cyclophosphamide, fluorouracil, and either doxorubicin or epirubicin. J Clin Oncol. 1988 Apr;6(4):679-88. [https://doi.org/10.1200/JCO.1988.6.4.679 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2895801 PubMed]
 
−
# Coombes RC, Bliss JM, Wils J, Morvan F, Espié M, Amadori D, Gambrosier P, Richards M, Aapro M, Villar-Grimalt A, McArdle C, Pérez-López FR, Vassilopoulos P, Ferreira EP, Chilvers CE, Coombes G, Woods EM, Marty M; International Collaborative Cancer Group. Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. J Clin Oncol. 1996 Jan;14(1):35-45. [https://doi.org/10.1200/JCO.1996.14.1.35 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8558217 PubMed]
 
−
# '''NCIC-CTG MA.5:''' Levine MN, Bramwell VH, Pritchard KI, Norris BD, Shepherd LE, Abu-Zahra H, Findlay B, Warr D, Bowman D, Myles J, Arnold A, Vandenberg T, MacKenzie R, Robert J, Ottaway J, Burnell M, Williams CK, Tu D; National Cancer Institute of Canada Clinical Trials Group. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. J Clin Oncol. 1998 Aug;16(8):2651-8. [https://doi.org/10.1200/jco.1998.16.8.2651 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9704715 PubMed]
 
−
## '''Update:''' Levine MN, Pritchard KI, Bramwell VH, Shepherd LE, Tu D, Paul N; National Cancer Institute of Canada Clinical Trials Group. Randomized trial comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials Group Trial MA5. J Clin Oncol. 2005 Aug 1;23(22):5166-70. [https://doi.org/10.1200/JCO.2005.09.423 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16051958 PubMed]
 
−
## '''Subgroup analysis:''' Pritchard KI, Shepherd LE, O'Malley FP, Andrulis IL, Tu D, Bramwell VH, Levine MN; National Cancer Institute of Canada Clinical Trials Group. HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med. 2006 May 18;354(20):2103-11. [https://doi.org/10.1056/NEJMoa054504 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16707747 PubMed]
 
−
# '''FASG 05:''' Bonneterre J; French Adjuvant Study Group. Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French Adjuvant Study Group 05 randomized trial. J Clin Oncol. 2001 Feb 1;19(3):602-11. [https://doi.org/10.1200/JCO.2001.19.3.602 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11157009 PubMed]
 
−
## '''Update:''' Bonneterre J, Roché H, Kerbrat P, Brémond A, Fumoleau P, Namer M, Goudier MJ, Schraub S, Fargeot P, Chapelle-Marcillac I. Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French Adjuvant Study Group 05 randomized trial. J Clin Oncol. 2005 Apr 20;23(12):2686-93. [https://doi.org/10.1200/JCO.2005.05.059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15837983 PubMed]
 
−
# Paradiso A, Schittulli F, Cellamare G, Mangia A, Marzullo F, Lorusso V, De Lena M. Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer. J Clin Oncol. 2001 Oct 1;19(19):3929-37. [https://doi.org/10.1200/JCO.2001.19.19.3929 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11579113 PubMed]
 
−
# '''EORTC 10902:''' van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organisation for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001 Nov 15;19(22):4224-37. [https://doi.org/10.1200/JCO.2001.19.22.4224 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11709566 PubMed]
 
−
## '''Update:''' van Nes JG, Putter H, Julien JP, Tubiana-Hulin M, van de Vijver M, Bogaerts J, de Vos M, van de Velde CJ; Cooperating Investigators of the EORTC. Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902. Breast Cancer Res Treat. 2009 May;115(1):101-13. Epub 2008 May 18. [https://doi.org/10.1007/s10549-008-0050-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18484198 PubMed]
 
−
# '''FASG 01:''' Fumoleau P, Kerbrat P, Romestaing P, Fargeot P, Brémond A, Namer M, Schraub S, Goudier MJ, Mihura J, Monnier A, Clavère P, Serin D, Seffert P, Pourny C, Facchini T, Jacquin JP, Sztermer JF, Datchary J, Ramos R, Luporsi E. Randomized trial comparing six versus three cycles of epirubicin-based adjuvant chemotherapy in premenopausal, node-positive breast cancer patients: 10-year follow-up results of the French Adjuvant Study Group 01 trial. J Clin Oncol. 2003 Jan 15;21(2):298-305. [https://doi.org/10.1200/JCO.2003.04.148 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12525522 PubMed]
 
−
# Arriagada R, Spielmann M, Koscielny S, Le Chevalier T, Delozier T, Rémé-Saumon M, Ducourtieux M, Tursz T, Hill C. Results of two randomized trials evaluating adjuvant anthracycline-based chemotherapy in 1146 patients with early breast cancer. Acta Oncol. 2005;44(5):458-66. [https://doi.org/10.1080/02841860510029987 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16118079 PubMed]
 
−
# '''ICCG HDT trial:''' Coombes RC, Howell A, Emson M, Peckitt C, Gallagher C, Bengala C, Tres A, Welch R, Lawton P, Rubens R, Woods E, Haviland J, Vigushin D, Kanfer E, Bliss JM. High dose chemotherapy and autologous stem cell transplantation as adjuvant therapy for primary breast cancer patients with four or more lymph nodes involved: long-term results of an international randomised trial. Ann Oncol. 2005 May;16(5):726-34. Epub 2005 Apr 7. [https://doi.org/10.1093/annonc/mdi166 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15817602 PubMed]
 
−
# '''MIG-1:''' Venturini M, Del Mastro L, Aitini E, Baldini E, Caroti C, Contu A, Testore F, Brema F, Pronzato P, Cavazzini G, Sertoli MR, Canavese G, Rosso R, Bruzzi P; Mammella InterGruppo. Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial. J Natl Cancer Inst. 2005 Dec 7;97(23):1724-33. [https://academic.oup.com/jnci/article/97/23/1724/2521486 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16333028 PubMed]
 
−
## '''Update:''' Blondeaux E, Lambertini M, Michelotti A, Conte B, Benasso M, Dellepiane C, Bighin C, Pastorino S, Levaggi A, Alonzo A, Poggio F, Buzzatti G, Molinelli C, Fregatti P, Bertoglio S, Boccardo F, Del Mastro L. Dose-dense adjuvant chemotherapy in early breast cancer patients: 15-year results of the Phase 3 Mammella InterGruppo (MIG)-1 study. Br J Cancer. 2020 May;122(11):1611-1617. Epub 2020 Mar 31. [https://doi.org/10.1038/s41416-020-0816-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7251109/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32231293 PubMed]
 
−
<!-- no pre-pub disclosed -->
 
−
# '''FinHer:''' Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. [https://doi.org/10.1056/NEJMoa053028 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16495393 PubMed] ISRCTN76560285
 
−
## '''Update:''' Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. [https://doi.org/10.1200/JCO.2008.21.4577 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19884557 PubMed]
 
−
# '''FASG 06:''' Roché H, Kerbrat P, Bonneterre J, Fargeot P, Fumoleau P, Monnier A, Clavère P, Goudier MJ, Chollet P, Guastalla JP, Serin D. Complete hormonal blockade versus epirubicin-based chemotherapy in premenopausal, one to three node-positive, and hormone-receptor positive, early breast cancer patients: 7-year follow-up results of French Adjuvant Study Group 06 randomised trial. Ann Oncol. 2006 Aug;17(8):1221-7. Epub 2006 May 26. [https://doi.org/10.1093/annonc/mdl107 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16731539 PubMed]
 
−
# '''FASG 03:''' Héry M, Bonneterre J, Roché H, Luporsi E, Kerbrat P, Namer M, Fumoleau P, Monnier A, Fargeot P. Epirubicin-based chemotherapy as adjuvant treatment for poor prognosis, node-negative breast cancer: 10-year follow-up results of the French Adjuvant Study Group 03 trial. Bull Cancer. 2006 Oct;93(10):E109-14. [http://www.jle.com/fr/revues/bdc/e-docs/epirubicin_based_chemotherapy_as_adjuvant_treatment_for_poor_prognosis_node_negative_breast_cancer_10_year_follow_up_results__272048/article.phtml link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17074656 PubMed]
 
−
# Rouëssé J, de la Lande B, Bertheault-Cvitkovic F, Serin D, Graïc Y, Combe M, Leduc B, Lucas V, Demange L, Nguyen TD, Castèra D, Krzisch C, Villet R, Mouret-Fourme E, Garbay JR, Noguès C; Centre René Huguenin Breast Cancer Group. A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: final results. Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1072-80. [https://doi.org/10.1016/S0360-3016(05)02813-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16504757 PubMed]
 
−
<!-- Presented in oral format at the 27th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-11, 2004. -->
 
−
# '''FNCLCC PACS 01:''' Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, Symann M, Kerbrat P, Soulié P, Eichler F, Viens P, Monnier A, Vindevoghel A, Campone M, Goudier MJ, Bonneterre J, Ferrero JM, Martin AL, Genève J, Asselain B. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006 Dec 20;24(36):5664-71. Epub 2006 Nov 20. [https://doi.org/10.1200/jco.2006.07.3916 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17116941 PubMed]
 
−
## '''Update:''' Coudert B, Asselain B, Campone M, Spielmann M, Machiels JP, Pénault-Llorca F, Serin D, Lévy C, Romieu G, Canon JL, Orfeuvre H, Piot G, Petit T, Jerusalem G, Audhuy B, Veyret C, Beauduin M, Eymard JC, Martin AL, Roché H; UNICANCER Breast Group. Extended benefit from sequential administration of docetaxel after standard fluorouracil, epirubicin, and cyclophosphamide regimen for node-positive breast cancer: the 8-year follow-up results of the UNICANCER-PACS01 trial. Oncologist. 2012;17(7):900-9. Epub 2012 May 18. [http://theoncologist.alphamedpress.org/content/17/7/900.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399644/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22610153 PubMed]
 
−
# '''DBCG 89D:''' Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Cold S, Edlund P, Ewertz M, Jensen BB, Kamby C, Nordenskjold B, Bergh J. Improved outcome from substituting methotrexate with epirubicin: results from a randomised comparison of CMF versus CEF in patients with primary breast cancer. Eur J Cancer. 2007 Mar;43(5):877-84. Epub 2007 Feb 16. [https://www.ejcancer.com/article/S0959-8049(07)00014-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17306974 PubMed]
 
−
# '''FASG 09:''' Kerbrat P, Roché H, Bonneterre J, Veyret C, Lortholary A, Monnier A, Fumoleau P, Fargeot P, Namer M, Chollet P, Goudier MJ, Audhuy B, Simon H, Montcuquet P, Eymard JC, Walter S, Clavère P, Guastalla JP; French Adjuvant Study Group. Epirubicin-vinorelbine vs FEC100 for node-positive, early breast cancer: French Adjuvant Study Group 09 trial. Br J Cancer. 2007 Jun 4;96(11):1633-8. Epub 2007 May 15. [https://www.nature.com/articles/6603773 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359910/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17505516 PubMed]
 
−
# '''GEICAM 9906:''' Martín M, Rodríguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Munárriz B, Rodríguez CA, Crespo C, de Alava E, López García-Asenjo JA, Guitián MD, Almenar S, González-Palacios JF, Vera F, Palacios J, Ramos M, Gracia Marco JM, Lluch A, Alvarez I, Seguí MA, Mayordomo JI, Antón A, Baena JM, Plazaola A, Modolell A, Pelegrí A, Mel JR, Aranda E, Adrover E, Alvarez JV, García Puche JL, Sánchez-Rovira P, Gonzalez S, López-Vega JM; GEICAM. Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Natl Cancer Inst. 2008 Jun 4;100(11):805-14. Epub 2008 May 27. [http://jnci.oxfordjournals.org/content/100/11/805.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18505968 PubMed] NCT00129922
 
−
# '''TACT:''' Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. [https://doi.org/10.1016/S0140-6736(09)60740-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687939/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19447249 PubMed] ISRCTN79718493
 
−
# Polyzos A, Malamos N, Boukovinas I, Adamou A, Ziras N, Kalbakis K, Kakolyris S, Syrigos K, Papakotoulas P, Kouroussis C, Karvounis N, Vamvakas L, Christophyllakis C, Athanasiadis A, Varthalitis I, Georgoulias V, Mavroudis D; Hellenic Oncology Research Group. FEC versus sequential docetaxel followed by epirubicin/cyclophosphamide as adjuvant chemotherapy in women with axillary node-positive early breast cancer: a randomized study of the Hellenic Oncology Research Group (HORG). Breast Cancer Res Treat. 2010 Jan;119(1):95-104. Epub 2009 Jul 28. [https://doi.org/10.1007/s10549-009-0468-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19636702 PubMed]
 
−
# '''NCIC-CTG MA.21:''' Burnell M, Levine MN, Chapman JA, Bramwell V, Gelmon K, Walley B, Vandenberg T, Chalchal H, Albain KS, Perez EA, Rugo H, Pritchard K, O'Brien P, Shepherd LE. Cyclophosphamide, epirubicin, and fluorouracil versus dose-dense epirubicin and cyclophosphamide followed by paclitaxel versus doxorubicin and cyclophosphamide followed by paclitaxel in node-positive or high-risk node-negative breast cancer. J Clin Oncol. 2010 Jan 1;28(1):77-82. Epub 2009 Nov 9. [https://doi.org/10.1200/JCO.2009.22.1077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799234/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19901117 PubMed] NCT00014222
 
−
# '''FNCLCC PACS 04:''' Spielmann M, Roché H, Delozier T, Canon JL, Romieu G, Bourgeois H, Extra JM, Serin D, Kerbrat P, Machiels JP, Lortholary A, Orfeuvre H, Campone M, Hardy-Bessard AC, Coudert B, Maerevoet M, Piot G, Kramar A, Martin AL, Penault-Llorca F. Trastuzumab for patients with axillary-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. J Clin Oncol. 2009 Dec 20;27(36):6129-34. Epub 2009 Nov 16. [https://doi.org/10.1200/jco.2009.23.0946 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19917839 PubMed] NCT00054587
 
−
## '''Update:''' D'Hondt V, Canon JL, Roca L, Levy C, Pierga JY, Le Du F, Campone M, Desmoulins I, Goncalves A, Debled M, Rios M, Ferrero JM, Serin D, Hardy-Bessard AC, Piot G, Brain E, Dohollou N, Orfeuvre H, Lemonnier J, Roché H, Delaloge S, Dalenc F. UCBG 2-04: Long-term results of the PACS 04 trial evaluating adjuvant epirubicin plus docetaxel in node-positive breast cancer and trastuzumab in the human epidermal growth factor receptor 2-positive subgroup. Eur J Cancer. 2019 Nov;122:91-100. Epub 2019 Oct 18. [https://doi.org/10.1016/j.ejca.2019.09.014 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31634648 PubMed]
 
−
# '''TRAFIC:''' Sirohi B, A'Hern R, Coombes G, Bliss JM, Hickish T, Perren T, Crawford M, O'Brien M, Iveson T, Ebbs S, Skene A, Laing R, Smith IE. A randomised comparative trial of infusional ECisF versus conventional FEC as adjuvant chemotherapy in early breast cancer: the TRAFIC trial. Ann Oncol. 2010 Aug;21(8):1623-9. Epub 2010 Jan 21. [https://doi.org/10.1093/annonc/mdp602 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20093351 PubMed] ISRCTN83324925
 
−
# Sakr H, Hamed RH, Anter AH, Yossef T. Sequential docetaxel as adjuvant chemotherapy for node-positive or/and T3 or T4 breast cancer: clinical outcome (Mansoura University). Med Oncol. 2013 Mar;30(1):457. Epub 2013 Jan 16. [https://doi.org/10.1007/s12032-013-0457-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23322524 PubMed]
 
−
# '''AERO-B2000:''' Delbaldo C, Serin D, Mousseau M, Greget S, Audhuy B, Priou F, Berdah JF, Teissier E, Laplaige P, Zelek L, Quinaux E, Buyse M, Piedbois P; Association Européenne de Recherche en Oncologie (AERO). A phase III adjuvant randomised trial of 6 cycles of 5-fluorouracil-epirubicine-cyclophosphamide (FEC100) versus 4 FEC 100 followed by 4 Taxol (FEC-T) in node positive breast cancer patients (Trial B2000). Eur J Cancer. 2014 Jan;50(1):23-30. Epub 2013 Oct 29. [https://www.ejcancer.com/article/S0959-8049(13)00898-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24183460 PubMed]
 
−
# '''WSG-AGO EC-Doc:''' Nitz U, Gluz O, Huober J, Kreipe HH, Kates RE, Hartmann A, Erber R, Moustafa Z, Scholz M, Lisboa B, Mohrmann S, Möbus V, Augustin D, Hoffmann G, Weiss E, Böhmer S, Kreienberg R, Du Bois A, Sattler D, Thomssen C, Kiechle M, Jänicke F, Wallwiener D, Harbeck N, Kuhn W. Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression. Ann Oncol. 2014 Aug;25(8):1551-7. Epub 2014 May 14. Erratum in: Ann Oncol. 2017 Nov 1;28(11):2899. [https://doi.org/10.1093/annonc/mdu186 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24827128 PubMed] NCT02115204
 
−
# '''GIM2:''' Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. Epub 2015 Mar 2. [https://doi.org/10.1016/s0140-6736(14)62048-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25740286 PubMed] NCT00433420
 
−
# '''GONO-MIG5:''' Del Mastro L, Levaggi A, Michelotti A, Cavazzini G, Adami F, Scotto T, Piras M, Danese S, Garrone O, Durando A, Accortanzo V, Bighin C, Miglietta L, Pastorino S, Pronzato P, Castiglione F, Landucci E, Conte P, Bruzzi P. 5-Fluorouracil, epirubicin and cyclophosphamide versus epirubicin and paclitaxel in node-positive early breast cancer: a phase-III randomized GONO-MIG5 trial. Breast Cancer Res Treat. 2016 Jan;155(1):117-26. [http://link.springer.com/article/10.1007/s10549-015-3655-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26661403 PubMed] NCT02450058
 
−
# '''ADEBAR:''' Janni W, Harbeck N, Rack B, Augustin D, Jueckstock J, Wischnik A, Annecke K, Scholz C, Huober J, Zwingers T, Friedl TW, Kiechle M. Randomised phase III trial of FEC120 vs EC-docetaxel in patients with high-risk node-positive primary breast cancer: final survival analysis of the ADEBAR study. Br J Cancer. 2016 Apr 12;114(8):863-71. Epub 2016 Mar 31. [https://www.nature.com/articles/bjc201682 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984804/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27031854 PubMed] NCT00047099
 
−
# '''HMFEC:''' Coombes RC, Kilburn LS, Tubiana-Mathieu N, Olmos T, Van Bochove A, Perez-Lopez FR, Palmieri C, Stebbing J, Bliss JM. Epirubicin dose and sequential hormonal therapy-Mature results of the HMFEC randomised phase III trial in premenopausal patients with node positive early breast cancer. Eur J Cancer. 2016 Jun;60:146-53. Epub 2016 Apr 26. [https://www.ejcancer.com/article/S0959-8049(16)00156-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27125966 PubMed] ISRCTN98335268
 
−
# '''UCBG-0106:''' Kerbrat P, Desmoulins I, Roca L, Levy C, Lortholary A, Marre A, Delva R, Rios M, Viens P, Brain É, Serin D, Edel M, Debled M, Campone M, Mourret-Reynier MA, Bachelot T, Foucher-Goudier MJ, Asselain B, Lemonnier J, Martin AL, Roché H. Optimal duration of adjuvant chemotherapy for high-risk node-negative (N-) breast cancer patients: 6-year results of the prospective randomised multicentre phase III UNICANCER-PACS 05 trial (UCBG-0106). Eur J Cancer. 2017 Jul;79:166-175. Epub 2017 May 11. [https://www.ejcancer.com/article/S0959-8049(17)30822-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28501763 PubMed]
 
−
# '''MINDACT:''' Delaloge S, Piccart M, Rutgers E, Litière S, van 't Veer LJ, van den Berkmortel F, Brain E, Dudek-Peric A, Gil-Gil M, Gomez P, Hilbers FS, Khalil Z, Knox S, Kuemmel S, Kunz G, Lesur A, Pierga JY, Ravdin P, Rubio IT, Saghatchian M, Smilde TJ, Thompson AM, Viale G, Zoppoli G, Vuylsteke P, Tryfonidis K, Poncet C, Bogaerts J, Cardoso F; MINDACT investigators and the TRANSBIG Consortium. Standard Anthracycline Based Versus Docetaxel-Capecitabine in Early High Clinical and/or Genomic Risk Breast Cancer in the EORTC 10041/BIG 3-04 MINDACT Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1186-1197. Epub 2020 Feb 21. [https://doi.org/10.1200/jco.19.01371 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/32083990 PubMed] NCT00433589
 
−
 
 
−
==MMM {{#subobject:5q18xa|Regimen=1}}==
 
−
 
 
−
MMM: '''<u>M</u>'''itomycin-C, '''<u>M</u>'''itoxantrone, '''<u>M</u>'''ethotrexate
 
−
===Regimen {{#subobject:8hgy1b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ Fernando et al. 2019 (SECRAB)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CMF_.26_RT_88|CMF & RT]]<br>2. [[#E-CMF_.26_RT_88|E-CMF & RT]]<br>3. [[#A-CMF_.26_RT_88|A-CMF & RT]]<br>4. [[#MMM_.26_RT_88|MMM & RT]]
 
−
| style="background-color:#d73027" |Inferior LRFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
 
 
−
====Chemotherapy====
 
−
*[[Mitomycin (Mutamycin)]] 8 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] 35 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
===References===
 
−
# '''SECRAB:''' Fernando IN, Bowden SJ, Herring K, Brookes CL, Ahmed I, Marshall A, Grieve R, Churn M, Spooner D, Latief TN, Agrawal RK, Brunt AM, Stevens A, Goodman A, Canney P, Bishop J, Ritchie D, Dunn J, Poole CJ, Rea DW; SECRAB Investigators. Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial. Radiother Oncol. 2020 Jan;142:52-61. Epub 2019 Nov 27. [https://doi.org/10.1016/j.radonc.2019.10.014 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7005671/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31785830/ PubMed] NCT00003893
 
−
 
 
−
==Paclitaxel monotherapy, weekly {{#subobject:5218a|Regimen=1}}==
 
−
 
 
−
T: '''<u>T</u>'''axol (Paclitaxel)
 
−
<br>P: '''<u>P</u>'''aclitaxel
 
−
<br>pT: '''<u>p</u>'''acli'''<u>T</u>'''axel
 
−
<br>wP: '''<u>w</u>'''eekly '''<u>P</u>'''aclitaxel
 
−
<br>wT: '''<u>w</u>'''eekly '''<u>T</u>'''axol (Paclitaxel)
 
−
===Regimen variant #1, 80 mg/m<sup>2</sup> x 12 {{#subobject:6b14dd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="3" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ Shulman et al. 2012 (CALGB 40101)]
 
−
| rowspan="3" |2002-2008
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|2. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 6
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|3. [[#Paclitaxel_monotherapy.2C_weekly|Paclitaxel]]; weekly x 18
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268253/ Budd et al. 2014 (SWOG S0221)]
 
−
|2003-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel monotherapy.2C_dose-dense_.28q2wk.29_2|ddT]] x 6
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2018.79.2028 Miller et al. 2018 (ECOG E5103)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#ECOG_E5103|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#ECOG_E5103|See link]]
 
−
|-
 
−
|}
 
−
''Note: In CALGB 40101, this is the dosing before a mid-protocol amendment in 2003. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*SWOG S0221: [[Surgery#Breast_cancer_surgery|Surgery]], then [[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 6 versus [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|continuous AC]]
 
−
*ECOG E5103: [[Surgery#Breast_cancer_surgery|Surgery]], then [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4 or [[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 4
 
−
 
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===Regimen variant #2, 100 mg/m<sup>2</sup> x 8 {{#subobject:d9efe7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.46.9841 Martín et al. 2013 (GEICAM 2003-02)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#GEICAM.2F2003-02|See link]]
 
−
|style="background-color:#91cf60" |[[Complex_multipart_regimens#GEICAM.2F2003-02|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*GEICAM 2003-02: [[Surgery#Breast_cancer_surgery|Surgery]], then [[#FAC_2|FAC]] x 4
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
 
−
'''28-day cycle for 2 cycles'''
 
−
 
 
−
===References===
 
−
# '''CALGB 40101:''' Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. [https://doi.org/10.1200/jco.2011.40.6405 link to original article] '''contains dosing details in manuscript''' [https://ascopubs.org/doi/suppl/10.1200/jco.2011.40.6405/suppl_file/Protocol.pdf link to study protocol PDF] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22826271 PubMed] NCT00041119
 
−
## '''Update:''' Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. [https://doi.org/10.1200/jco.2013.53.7142 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105484/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24934787 PubMed]
 
−
# '''GEICAM 2003-02:''' Martín M, Ruiz A, Ruiz Borrego M, Barnadas A, González S, Calvo L, Margelí Vila M, Antón A, Rodríguez-Lescure A, Seguí-Palmer MA, Muñoz-Mateu M, Dorca Ribugent J, López-Vega JM, Jara C, Espinosa E, Mendiola Fernández C, Andrés R, Ribelles N, Plazaola A, Sánchez-Rovira P, Salvador Bofill J, Crespo C, Carabantes FJ, Servitja S, Chacón JI, Rodríguez CA, Hernando B, Álvarez I, Carrasco E, Lluch A. Fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus FAC followed by weekly paclitaxel as adjuvant therapy for high-risk, node-negative breast cancer: results from the GEICAM/2003-02 study. J Clin Oncol. 2013 Jul 10;31(20):2593-9. Epub 2013 Jun 3. [https://doi.org/10.1200/jco.2012.46.9841 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23733779 PubMed] NCT00129389
 
−
# '''SWOG S0221:''' Budd GT, Barlow WE, Moore HC, Hobday TJ, Stewart JA, Isaacs C, Salim M, Cho JK, Rinn KJ, Albain KS, Chew HK, Burton GV, Moore TD, Srkalovic G, McGregor BA, Flaherty LE, Livingston RB, Lew DL, Gralow JR, Hortobagyi GN. SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. J Clin Oncol. 2015 Jan 1;33(1):58-64. Epub 2014 Nov 24. [https://doi.org/10.1200/JCO.2014.56.3296 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268253/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25422488 PubMed] NCT00070564
 
−
# '''ECOG E5103:''' Miller KD, O'Neill A, Gradishar W, Hobday TJ, Goldstein LJ, Mayer IA, Bloom S, Brufsky AM, Tevaarwerk AJ, Sparano JA, Le-Lindqwister NA, Hendricks CB, Northfelt DW, Dang CT, Sledge GW Jr. Double-blind phase III trial of adjuvant chemotherapy with and without bevacizumab in patients with lymph node-positive and high-risk lymph node-negative breast cancer (E5103). J Clin Oncol. 2018 Sep 1;36(25):2621-2629. Epub 2018 Jul 24. [https://doi.org/10.1200/JCO.2018.79.2028 link to original article] '''refers to ECOG E1199 protocol''' [https://pubmed.ncbi.nlm.nih.gov/30040523 PubMed] NCT00433511
 
−
 
 
−
==Paclitaxel monotherapy, dose-dense (q2wk) {{#subobject:8acb30|Regimen=1}}==
 
−
 
 
−
ddT: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>T</u>'''axol (Paclitaxel)
 
−
<br>ddP: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>P</u>'''aclitaxel
 
−
===Regimen variant #1, 175 mg/m<sup>2</sup> x 4 {{#subobject:d853ac|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.09.081 Citron et al. 2003 (CALGB 9741)]
 
−
|1997-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
−
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
−
|-
 
−
| rowspan="3" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ Shulman et al. 2012 (CALGB 40101)]
 
−
| rowspan="3" |2002-2008
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 4
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|2. [[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 6
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|3. [[#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|ddT]] x 6
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.02.8621 Burstein et al. 2005]
 
−
|2003-2004
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(14)62048-1 Del Mastro et al. 2015 (GIM2)]
 
−
|2003-2006
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#GIM2|See link]]
 
−
|[[Complex_multipart_regimens#GIM2|See link]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ Swain et al. 2013 (NSABP B-38)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#NSABP_B-38|See link]]
 
−
|[[Complex_multipart_regimens#NSABP_B-38|See link]]
 
−
|-
 
−
|}
 
−
''Note: in CALGB 40101, this is the dosing after a mid-protocol amendment in 2003.''
 
−
====Preceding treatment====
 
−
*CALGB 9741: [[#Dose-dense_Doxorubicin_monotherapy|ddA]] x 4
 
−
*Burstein et al. 2005: Neoadjuvant [[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29|ddAC]], then [[Surgery#Breast_cancer_surgery|surgery]] or [[Surgery#Breast_cancer_surgery|surgery]], then adjuvant [[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]]
 
−
*CALGB 40101: [[Surgery#Breast_cancer_surgery|Surgery]], within 90 days
 
−
*NSABP B-38: [[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 4
 
−
*GIM2: [[#Dose-dense_Cyclophosphamide_.26_Epibicin_.28ddEC.29|ddEC]] x 4 versus [[#Dose-dense_FEC|ddFEC]] x 4
 
−
 
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Diphenhydramine (Benadryl)]] 12.5 to 50 mg IV once on day 1; 30 to 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
*One of the following H2 blockers:
 
−
**[[Ranitidine (Zantac)]] 50 mg IV once on day 1; 30 to 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
**[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 to 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
**[[Famotidine (Pepcid)]] 20 mg IV once on day 1; 30 to 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
*One of the following dexamethasone choices:
 
−
**[[Dexamethasone (Decadron)]] 10 mg IV once on day 1, within 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
**[[Dexamethasone (Decadron)]] 10 mg PO once on day 1, at least 60 minutes prior to [[Paclitaxel (Taxol)]]
 
−
**[[Dexamethasone (Decadron)]] 20 mg PO twice on day 1; 6 hours and 12 hours prior to [[Paclitaxel (Taxol)]]
 
−
*Recommended growth factor support with one of the following:
 
−
**[[Filgrastim (Neupogen)]] 5 mcg/kg (rounded to 300 mcg or 480 mcg, whichever is closer) SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
 
−
**[[Sargramostim (Leukine)]] 250 to 500 mcg/m<sup>2</sup> SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
 
−
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once, given 24 to 36 hours after chemotherapy
 
−
***GIM2: a mid-protocol amendment suggested giving the pegilgrastim at least 72 h after chemotherapy
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
 
 
−
====Subsequent treatment====
 
−
*CALGB 9741: [[#Dose-dense_Cyclophosphamide_monotherapy|ddC]] x 4
 
−
===Regimen variant #2, 175 mg/m<sup>2</sup> x 6 {{#subobject:33516a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268253/ Budd et al. 2014 (SWOG S0221)]
 
−
|2003-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Paclitaxel_monotherapy.2C_weekly|Paclitaxel]]; weekly
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 6 versus [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|continuous AC]]
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
 
−
 
 
−
'''14-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #3, 200 mg/m<sup>2</sup> x 4 {{#subobject:6a0bb6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.karger.com/Article/Abstract/86987 Kahan et al. 2005]
 
−
|2000-2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[#Dose-dense_Doxorubicin_monotherapy|ddA]] x 4
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]]
 
−
 
 
−
'''14-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Dose-dense_Cyclophosphamide_monotherapy|ddC]]
 
−
 
 
−
===References===
 
−
# '''CALGB 9741:''' Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. [https://doi.org/10.1200/jco.2003.09.081 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12668651 PubMed] NCT00003088
 
−
# Kahan Z, Uhercsak G, Hajnal-Papp R, Boda K, Thurzo L. Dose-dense sequential adriamycin-paclitaxel-cyclophosphamide chemotherapy is well tolerated and safe in high-risk early breast cancer. Oncology. 2005;68(4-6):446-53. Epub 2005 Jul 13. [http://www.karger.com/Article/Abstract/86987 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16020975 PubMed]
 
−
## '''Update:''' Kelemen G, Uhercsák G, Ormándi K, Eller J, Thurzó L, Kahán Z. Long-term efficiency and toxicity of adjuvant dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy in high-risk breast cancer. Oncology. 2010;78(3-4):271-3. Epub 2010 Jun 7. [https://doi.org/10.1159/000315734 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20523088 PubMed]
 
−
# Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. [https://doi.org/10.1200/jco.2005.02.8621 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16293865 PubMed]
 
−
# '''CALGB 40101:''' Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. [https://doi.org/10.1200/jco.2011.40.6405 link to original article] '''contains dosing details in manuscript''' [https://ascopubs.org/doi/suppl/10.1200/jco.2011.40.6405/suppl_file/Protocol.pdf link to study protocol PDF] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22826271 PubMed] NCT00041119
 
−
## '''Update:''' Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. [https://doi.org/10.1200/jco.2013.53.7142 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105484/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24934787 PubMed]
 
−
# '''NSABP B-38:''' Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. Epub 2013 Aug 12. [https://doi.org/10.1200/JCO.2012.48.1275 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23940225 PubMed] NCT00093795
 
−
# '''SWOG S0221:''' Budd GT, Barlow WE, Moore HC, Hobday TJ, Stewart JA, Isaacs C, Salim M, Cho JK, Rinn KJ, Albain KS, Chew HK, Burton GV, Moore TD, Srkalovic G, McGregor BA, Flaherty LE, Livingston RB, Lew DL, Gralow JR, Hortobagyi GN. SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. J Clin Oncol. 2015 Jan 1;33(1):58-64. Epub 2014 Nov 24. [https://doi.org/10.1200/JCO.2014.56.3296 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268253/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25422488 PubMed] NCT00070564
 
−
# '''GIM2:''' Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. Epub 2015 Mar 2. [https://doi.org/10.1016/s0140-6736(14)62048-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25740286 PubMed] NCT00433420
 
−
 
 
−
==TAC (Docetaxel) {{#subobject:ed77a6|Regimen=1}}==
 
−
 
 
−
TAC: '''<u>T</u>'''axotere (Docetaxel), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
 
−
<br>ACT: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''axotere (Docetaxel)
 
−
===Regimen variant #1, 4 cycles {{#subobject:36e78d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935316/ Swain et al. 2010 (NSABP B-30)]
 
−
|rowspan=2|1999-2004
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#AC-D_2|AC-D]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|2. [[#Docetaxel_.26_Doxorubicin_.28AT.29_99|AT]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
''Note: this was a mid-protocol dosing amendment.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV over 15 minutes once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV over 1 to 5 minutes once on day 1
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
 
 
−
===Regimen variant #2, 6 cycles {{#subobject:9660e9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa043681 Martin et al. 2005 (BCIRG 001)]
 
−
|1997-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#FAC_2|FAC]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS120: 76% vs 69%<br>(HR 0.74, 95% CI 0.61-0.90)
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa0910320 Martín et al. 2010 (GEICAM 9805)]
 
−
|1999-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#FAC_2|FAC]]
 
−
| style="background-color:#1a9850" |Superior DFS <br>(HR 0.68, 95% CI 0.49-0.93)
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2010.28.5437 Eiermann et al. 2011 (BCIRG-005)]
 
−
|2000-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#AC-D_2|AC-D]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|-
 
−
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ Swain et al. 2013 (NSABP B-38)]
 
−
| rowspan="2" |2004-2007
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]], then [[#Paclitaxel monotherapy.2C_dose-dense_.28q2wk.29_2|ddP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|2. [[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]], then ddPG
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(18)30982-1 van Rossum et al. 2018 (MATADOR)]
 
−
|2004-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]]
 
−
| style="background-color:#ffffbf" |Did not meet secondary endpoints of RFS/OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ Blum et al. 2017 (USOR 06-090)]
 
−
|2007-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Docetaxel_.28TC.29|TC]]
 
−
| style="background-color:#91cf60" |Seems to have superior IDFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ Blum et al. 2017 (NSABP-46-I/USOR 07132)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Docetaxel_.28TC.29|TC]]
 
−
| style="background-color:#91cf60" |Seems to have superior IDFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ Blum et al. 2017 (NSABP B-49)]
 
−
|2012-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Docetaxel_.28TC.29|TC]]
 
−
| style="background-color:#91cf60" |Seems to have superior IDFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2012 update.''<br>
 
−
''Note: Blum et al. 2017 is a pooled analysis of three RCTs, some of which had arms other than TAC and TC. Refer to the paper for further details.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given third, one hour after cyclophosphamide'''
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV over 15 minutes once on day 1, '''given first'''
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV over 1 to 5 minutes once on day 1, '''given second'''
 
−
 
 
−
====Supportive therapy====
 
−
*[[Dexamethasone (Decadron)]] 8 mg PO every 12 hours for 6 total doses, starting the day before treatment
 
−
*[[Ciprofloxacin (Cipro)]] 500 mg PO twice per day on days 5 to 14
 
−
*G-CSF not originally routinely administered unless patients had febrile neutropenia, but some guidelines recommend one of the following:
 
−
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 4 to 11
 
−
**[[Lenograstim (Granocyte)]] 150 mcg/m<sup>2</sup> SC once per day on days 4 to 11
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===References===
 
−
<!-- no pre-pub disclosed -->
 
−
# '''BCIRG 001:''' Martín M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, Guevin R, Howell A, Fornander T, Hainsworth J, Coleman R, Vinholes J, Modiano M, Pinter T, Tang SC, Colwell B, Prady C, Provencher L, Walde D, Rodriguez-Lescure A, Hugh J, Loret C, Rupin M, Blitz S, Jacobs P, Murawsky M, Riva A, Vogel C; Breast Cancer International Research Group. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13. [https://doi.org/10.1056/NEJMoa043681 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15930421 PubMed] NCT00688740
 
−
## '''Update:''' Mackey JR, Martín M, Pienkowski T, Rolski J, Guastalla JP, Sami A, Glaspy J, Juhos E, Wardley A, Fornander T, Hainsworth J, Coleman R, Modiano MR, Vinholes J, Pinter T, Rodríguez-Lescure A, Colwell B, Whitlock P, Provencher L, Laing K, Walde D, Price C, Hugh JC, Childs BH, Bassi K, Lindsay MA, Wilson V, Rupin M, Houé V, Vogel C; TRIO/BCIRG 001 investigators. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol. 2013 Jan;14(1):72-80. Epub 2012 Dec 12. [https://doi.org/10.1016/S1470-2045(12)70525-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23246022 PubMed]
 
−
# '''NSABP B-30:''' Swain SM, Jeong JH, Geyer CE Jr, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff J, Vogel VG, Erban JK, Rastogi P, Livingston RB, Perez EA, Mamounas EP, Land SR, Ganz PA, Wolmark N. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med. 2010 Jun 3;362(22):2053-65. [https://doi.org/10.1056/NEJMoa0909638 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935316/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20519679 PubMed] NCT00003782
 
−
<!-- no pre-pub disclosed -->
 
−
# '''GEICAM 9805:''' Martín M, Seguí MA, Antón A, Ruiz A, Ramos M, Adrover E, Aranda I, Rodríguez-Lescure A, Grosse R, Calvo L, Barnadas A, Isla D, Martinez del Prado P, Ruiz Borrego M, Zaluski J, Arcusa A, Muñoz M, López Vega JM, Mel JR, Munarriz B, Llorca C, Jara C, Alba E, Florián J, Li J, López García-Asenjo JA, Sáez A, Rios MJ, Almenar S, Peiró G, Lluch A; GEICAM. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med. 2010 Dec 2;363(23):2200-10. [https://doi.org/10.1056/NEJMoa0910320 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21121833 PubMed] NCT00121992
 
−
<!-- Presented in part at the 28th Annual San Antonio Breast Cancer Symposia, December 8-11, 2005, San Antonio, TX, and at the 31st Annual San Antonio Breast Cancer Symposia, December 10-14, 2008, San Antonio, TX. -->
 
−
# '''BCIRG-005:''' Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martín M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press M, Sauter G, Lindsay MA, Riva A, Buyse M, Drevot P, Taupin H, Mackey JR. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011 Oct 10;29(29):3877-84. Epub 2011 Sep 12. [https://doi.org/10.1200/jco.2010.28.5437 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21911726 PubMed] NCT00312208
 
−
## '''Update:''' Mackey JR, Pieńkowski T, Crown J, Sadeghi S, Martín M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press MF, Sauter G, Lindsay M, Houé V, Buyse M, Drevot P, Hitier S, Bensfia S, Eiermann W; Translational Research In Oncology (TRIO)/ Breast Cancer International Research Group (BCIRG)-005 investigators. Long-term outcomes after adjuvant treatment of sequential versus combination docetaxel with doxorubicin and cyclophosphamide in node-positive breast cancer: BCIRG-005 randomized trial. Ann Oncol. 2016 Jun;27(6):1041-7. Epub 2016 Mar 2. [https://doi.org/10.1093/annonc/mdw098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26940688 PubMed]
 
−
# '''NSABP B-38:''' Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. Epub 2013 Aug 12. [https://doi.org/10.1200/JCO.2012.48.1275 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23940225 PubMed] NCT00093795
 
−
# '''USOR 06-090:''' Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, Robert NJ, Hopkins JO, O'Shaughnessy JA, Dang CT, Gómez HL, Fehrenbacher L, Vukelja SJ, Lyss AP, Paul D, Brufsky AM, Jeong JH, Colangelo LH, Swain SM, Mamounas EP, Jones SE, Wolmark N. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-2655. Epub 2017 Apr 11. [https://doi.org/10.1200/JCO.2016.71.4147 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28398846 PubMed] NCT00493870
 
−
# '''NSABP-46-I/USOR 07132:''' Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, Robert NJ, Hopkins JO, O'Shaughnessy JA, Dang CT, Gómez HL, Fehrenbacher L, Vukelja SJ, Lyss AP, Paul D, Brufsky AM, Jeong JH, Colangelo LH, Swain SM, Mamounas EP, Jones SE, Wolmark N. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-2655. Epub 2017 Apr 11. [https://doi.org/10.1200/JCO.2016.71.4147 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28398846 PubMed] NCT00887536
 
−
# '''NSABP B-49:''' Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, Robert NJ, Hopkins JO, O'Shaughnessy JA, Dang CT, Gómez HL, Fehrenbacher L, Vukelja SJ, Lyss AP, Paul D, Brufsky AM, Jeong JH, Colangelo LH, Swain SM, Mamounas EP, Jones SE, Wolmark N. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-2655. Epub 2017 Apr 11. [https://doi.org/10.1200/JCO.2016.71.4147 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28398846 PubMed] NCT01547741
 
−
# '''MATADOR:''' van Rossum AGJ, Kok M, van Werkhoven E, Opdam M, Mandjes IAM, van Leeuwen-Stok AE, van Tinteren H, Imholz ALT, Portielje JEA, Bos MMEM, van Bochove A, Wesseling J, Rutgers EJ, Linn SC, Oosterkamp HM; MATADOR Trialists' Group. Adjuvant dose-dense doxorubicin-cyclophosphamide versus docetaxel-doxorubicin-cyclophosphamide for high-risk breast cancer: first results of the randomised MATADOR trial (BOOG 2004-04). Eur J Cancer. 2018 Oct;102:40-48. [https://www.ejcancer.com/article/S0959-8049(18)30982-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30125761 PubMed] ISRCTN61893718
 
−
 
 
−
==Vinorelbine monotherapy {{#subobject:84c1e0|Regimen=1}}==
 
−
 
 
−
V: '''<u>V</u>'''inorelbine
 
−
===Regimen {{#subobject:712969|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa053028 Joensuu et al. 2006 (FinHer)]
 
−
|2000-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Docetaxel_monotherapy|Docetaxel]]
 
−
| style="background-color:#d73027" |Inferior DDFS
 
−
|-
 
−
|}
 
−
''Note: Patients without HER2/neu amplification were only randomized to this arm verus the docetaxel arm.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Chemotherapy====
 
−
*[[Vinorelbine (Navelbine)]] as follows:
 
−
**Cycles 1 & 2: 25 mg/m<sup>2</sup> IV over 5 to 10 minutes once per day on days 1, 8, 15
 
−
**Cycle 3: 25 mg/m<sup>2</sup> IV over 5 to 10 minutes once per day on days 1 & 8
 
−
 
 
−
'''21-day cycle for 3 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#FEC_2|FEC]]
 
−
 
 
−
===References===
 
−
<!-- no pre-pub disclosed -->
 
−
# '''FinHer:''' Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. [https://doi.org/10.1056/NEJMoa053028 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16495393 PubMed] ISRCTN76560285
 
−
## '''Update:''' Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. [https://doi.org/10.1200/JCO.2008.21.4577 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19884557 PubMed]
 
−
 
 
−
=Metastatic disease, first-line chemotherapy=
 
−
'''''Note: in many of these regimens, patients were allowed to have received (neo)adjuvant chemotherapy and hormonal therapy (when applicable). These are first-line regimens in the metastatic setting, with a few being specifically for the locally advanced but unresectable setting.''
 
−
==Cyclophosphamide & Doxorubicin (AC) {{#subobject:843320|Regimen=1}}==
 
−
 
 
−
AC: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide
 
−
===Regimen variant #1, 40/400 {{#subobject:2e4988|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O Rosner et al. 1987]
 
−
|1981-1985
 
−
| style="background-color:#1a9851" |Randomized (E-de-esc)
 
−
|1. [[Breast_cancer_-_historical#CFP_2|CFP]]<br> 2. [[Breast_cancer_-_historical#CMFVP_2|CMFVP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #2, 40/500 {{#subobject:2e4988|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdn781 Katsumata et al. 2009 (JCOG9802)]
 
−
|1999-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#AC.2FD_99|AC/D]]<br> 2. [[#Docetaxel_monotherapy_2|Docetaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #3, 40/800 (PO) {{#subobject:136e1b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197507)36:1%3C90::AID-CNCR2820360104%3E3.0.CO;2-H Jones et al. 1975]
 
−
|1973-1974
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19820301)49:5%3C835::AID-CNCR2820490502%3E3.0.CO;2-Z Tranum et al. 1982 (SWOG-7405B)]
 
−
|1974-1977
 
−
|style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#FAC_3|FAC]]<br> 2. [[#Doxorubicin_monotherapy_2|A]], then [[Breast_cancer_-_historical#CMFVP_2|CMFVP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup>/day PO in divided doses on days 3 to 6
 
−
 
 
−
'''21- to 28-day cycles'''
 
−
 
 
−
===Regimen variant #4, 50/750 {{#subobject:2e4755|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1986.4.2.186 Forbes 1986]
 
−
|1978-1981
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|1. [[Breast_cancer_-_historical#ACT|ACT]]<br> 2. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_3|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 9 cycles'''
 
−
 
 
−
===Regimen variant #5, 60/600 {{#subobject:2e4988|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2002.11.005 Biganzoli et al. 2002 (EORTC 10961)]
 
−
|1996-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Paclitaxel_.28AT.29_2|AT (Taxol)]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.04.040 Nabholtz et al. 2003 (TAX 306)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Doxorubicin_.28AT.29|AT (Taxotere)]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles (see note)'''
 
−
 
 
−
===Regimen variant #6, with range {{#subobject:900e58|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_.26_Bevacizumab_2|AC & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 50 to 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 8 cycles'''
 
−
===References===
 
−
# Jones SE, Durie BG, Salmon SE. Combination chemotherapy with adriamycin and cyclophosphamide for advanced breast cancer. Cancer. 1975 Jul;36(1):90-7. [https://doi.org/10.1002/1097-0142(197507)36:1%3C90::AID-CNCR2820360104%3E3.0.CO;2-H link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1203853 PubMed]
 
−
# '''SWOG-7405B:''' Tranum BL, McDonald B, Thigpen T, Vaughn C, Wilson H, Maloney T, Costanzi J, Bickers J, el Mawli NG, Palmer R, Hoogstraten B, Heilburn L, Rasmusen S; [[Study_Groups#SWOG|SWOG]]. Adriamycin combinations in advanced breast cancer: a Southwest Oncology Group Study. Cancer. 1982 Mar 1;49(5):835-9. [https://doi.org/10.1002/1097-0142(19820301)49:5%3C835::AID-CNCR2820490502%3E3.0.CO;2-Z link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7037152 PubMed]
 
−
# Forbes JF; Australian and New Zealand Breast Cancer Trials Group, Clinical Oncological Society of Australia. A randomized trial in postmenopausal patients with advanced breast cancer comparing endocrine and cytotoxic therapy given sequentially or in combination. J Clin Oncol. 1986 Feb;4(2):186-93. [https://doi.org/10.1200/JCO.1986.4.2.186 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2868074 PubMed]
 
−
# Rosner D, Nemoto T, Lane WW. A randomized study of intensive versus moderate chemotherapy programs in metastatic breast cancer. Cancer. 1987 Mar 1;59(5):874-83. [https://doi.org/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3815266 PubMed]
 
−
# '''EORTC 10961:''' Biganzoli L, Cufer T, Bruning P, Coleman R, Duchateau L, Calvert AH, Gamucci T, Twelves C, Fargeot P, Epelbaum R, Lohrisch C, Piccart MJ. Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: The European Organisation for Research and Treatment of Cancer 10961 multicenter phase III trial. J Clin Oncol. 2002 Jul 15;20(14):3114-21. [https://doi.org/10.1200/JCO.2002.11.005 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12118025 PubMed]
 
−
# '''TAX 306:''' Nabholtz JM, Falkson C, Campos D, Szanto J, Martín M, Chan S, Pienkowski T, Zaluski J, Pinter T, Krzakowski M, Vorobiof D, Leonard R, Kennedy I, Azli N, Murawsky M, Riva A, Pouillart P; TAX 306 Study Group. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol. 2003 Mar 15;21(6):968-75. [https://doi.org/10.1200/jco.2003.04.040 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12637459 PubMed]
 
−
# '''JCOG9802:''' Katsumata N, Watanabe T, Minami H, Aogi K, Tabei T, Sano M, Masuda N, Andoh J, Ikeda T, Shibata T, Takashima S. Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel, and alternating AC and docetaxel as front-line chemotherapy for metastatic breast cancer: Japan Clinical Oncology Group trial (JCOG9802). Ann Oncol. 2009 Jul;20(7):1210-5. Epub 2009 Mar 2. [https://doi.org/10.1093/annonc/mdn781 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19254942 PubMed]
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
 
 
−
==Cyclophosphamide & Doxorubicin (AC) & Bevacizumab {{#subobject:843320|Regimen=1}}==
 
−
 
 
−
AC & Bevacizumab: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, Bevacizumab
 
−
===Regimen variant #1, with range {{#subobject:900e58|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_3|AC]]
 
−
| style="background-color:#1a9850" |Superior PFS <br>(HR 0.64, 95% CI 0.52-0.80)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 50 to 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Bevacizumab_monotherapy_2|Bevacizumab]] maintenance, if no PD
 
−
 
 
−
===References===
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
 
 
−
==Capecitabine monotherapy {{#subobject:842c42|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, 650 mg/m<sup>2</sup> PO twice per day, continuous {{#subobject:45bb7c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2010.33.9101 Stockler et al. 2011 (ANZ 0001)]
 
−
|rowspan=2|2001-2005
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#CMF_2|CMF]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|2. [[#Capecitabine_monotherapy_2|Capecitabine]]; intermittent
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of quality-adjusted PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 650 mg/m<sup>2</sup> PO twice per day
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #2, 1000 mg/m<sup>2</sup> PO twice per day, limited duration {{#subobject:698b2d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433520/ Smorenburg et al. 2014 (OMEGA)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #3, 1000 mg/m<sup>2</sup> PO twice per day, indefinite {{#subobject:674c2d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.02.167 Bajetta et al. 2005]
 
−
|1999-2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2010.33.9101 Stockler et al. 2011 (ANZ 0001)]
 
−
|rowspan=2|2001-2005
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#CMF_2|CMF]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|2. [[#Capecitabine_monotherapy_2|Capecitabine]]; continuous
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of quality-adjusted PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Bevacizumab|Capecitabine & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #4, 1250 mg/m<sup>2</sup> PO twice per day {{#subobject:fb2810|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.02.167 Bajetta et al. 2005]
 
−
|1999-2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222915/ Harbeck et al. 2016 (PELICAN)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior TTP
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*JO21095: [[#Docetaxel_monotherapy_3|Docetaxel]], with progression
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# Bajetta E, Procopio G, Celio L, Gattinoni L, Della Torre S, Mariani L, Catena L, Ricotta R, Longarini R, Zilembo N, Buzzoni R. Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol. 2005 Apr 1;23(10):2155-61. Epub 2005 Feb 14. [https://doi.org/10.1200/jco.2005.02.167 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15710946 PubMed]
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
<!-- Presented in part at the 29th Annual San Antonio Breast Cancer Symposium, December 14-17, 2006, San Antonio, TX, and 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL. -->
 
−
# '''ANZ 0001:''' Stockler MR, Harvey VJ, Francis PA, Byrne MJ, Ackland SP, Fitzharris B, Van Hazel G, Wilcken NR, Grimison PS, Nowak AK, Gainford MC, Fong A, Paksec L, Sourjina T, Zannino D, Gebski V, Simes RJ, Forbes JF, Coates AS. Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4498-504. Epub 2011 Oct 24. [https://doi.org/10.1200/jco.2010.33.9101 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22025143 PubMed]
 
−
# '''OMEGA:''' Smorenburg CH, de Groot SM, van Leeuwen-Stok AE, Hamaker ME, Wymenga AN, de Graaf H, de Jongh FE, Braun JJ, Los M, Maartense E, van Tinteren H, Nortier JW, Seynaeve C; Dutch Breast Cancer Research Group. A randomized phase III study comparing pegylated liposomal doxorubicin with capecitabine as first-line chemotherapy in elderly patients with metastatic breast cancer: results of the OMEGA study of the Dutch Breast Cancer Research Group BOOG. Ann Oncol. 2014 Mar;25(3):599-605. Epub 2014 Feb 6. [https://doi.org/10.1093/annonc/mdt588 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433520/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24504445 PubMed] ISRCTN11114726
 
−
# '''PELICAN:''' Harbeck N, Saupe S, Jäger E, Schmidt M, Kreienberg R, Müller L, Otremba BJ, Waldenmaier D, Dorn J, Warm M, Scholz M, Untch M, de Wit M, Barinoff J, Lück HJ, Harter P, Augustin D, Harnett P, Beckmann MW, Al-Batran SE; PELICAN Investigators. A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. Breast Cancer Res Treat. 2017 Jan;161(1):63-72. Epub 2016 Oct 31. [https://doi.org/10.1007/s10549-016-4033-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222915/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27798749 PubMed] NCT00266799
 
−
# '''CONTESSA:''' NCT03326674
 
−
 
 
−
==Capecitabine & Bevacizumab {{#subobject:14a8f1|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:b1de3e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Capecitabine_monotherapy_2|Capecitabine]]
 
−
| style="background-color:#1a9850" |Superior PFS <br>(HR 0.69, 95% CI 0.56-0.84)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70566-1 Lang et al. 2013 (TURANDOT)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#eeee01" |Non-inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788680/ Welt et al. 2016 (CARIN)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine.2C_Vinorelbine.2C_Bevacizumab_88|Capecitabine, Vinorelbine, Bevacizumab]]
 
−
| style="background-color:#fee08b" |Might have inferior PFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for TURANDOT is based on the 2016 update.''
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
# '''TURANDOT:''' Lang I, Brodowicz T, Ryvo L, Kahan Z, Greil R, Beslija S, Stemmer SM, Kaufman B, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Messinger D, Zielinski C; Central European Cooperative Oncology Group. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial. Lancet Oncol. 2013 Feb;14(2):125-33. Epub 2013 Jan 10. [https://doi.org/10.1016/S1470-2045(12)70566-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23312888 PubMed] NCT00600340
 
−
## '''Update:''' Zielinski C, Láng I, Inbar M, Kahán Z, Greil R, Beslija S, Stemmer SM, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Petruzelka L, Eniu A, Nisenbaum B, Dank M, Anghel R, Messinger D, Brodowicz T; TURANDOT investigators. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. Lancet Oncol. 2016 Sep;17(9):1230-9. Epub 2016 Aug 5. [https://doi.org/10.1016/S1470-2045(16)30154-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27501767 PubMed]
 
−
# '''CARIN:''' Welt A, Marschner N, Lerchenmueller C, Decker T, Steffens CC, Koehler A, Depenbusch R, Busies S, Hegewisch-Becker S. Capecitabine and bevacizumab with or without vinorelbine in first-line treatment of HER2/neu-negative metastatic or locally advanced breast cancer: final efficacy and safety data of the randomised, open-label superiority phase 3 CARIN trial. Breast Cancer Res Treat. 2016 Feb;156(1):97-107. [https://doi.org/10.1007/s10549-016-3727-x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788680/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26927446 PubMed] NCT00868634
 
−
 
 
−
==Capecitabine & Paclitaxel {{#subobject:bd0f63|Regimen=1}}==
 
−
 
 
−
TX: '''<u>T</u>'''axol (Paclitaxel), '''<u>X</u>'''eloda (Capecitabine)
 
−
===Regimen {{#subobject:74e9d|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.05.1383 Blum et al. 2006]
 
−
|2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> (rounded to nearest 500 mg) PO twice per day on days 1 to 14
 
−
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# Blum JL, Dees EC, Chacko A, Doane L, Ethirajan S, Hopkins J, McMahon R, Merten S, Negron A, Neubauer M, Ilegbodu D, Boehm KA, Asmar L, O'Shaughnessy JA. Phase II trial of capecitabine and weekly paclitaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2006 Sep 20;24(27):4384-90. Epub 2006 Aug 22. [https://doi.org/10.1200/jco.2005.05.1383 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16926223 PubMed]
 
−
 
 
−
==Capecitabine & Paclitaxel, nanoparticle albumin-bound {{#subobject:821a8e|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:e2b0d2|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.clinical-breast-cancer.com/article/S1526-8209(11)00206-0 Schwartzberg et al. 2011]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> (rounded to nearest 500 mg) PO twice per day on days 1 to 15
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 125 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# Schwartzberg LS, Arena FP, Mintzer DM, Epperson AL, Walker MS. Phase II multicenter trial of albumin-bound paclitaxel and capecitabine in first-line treatment of patients with metastatic breast cancer. Clin Breast Cancer. 2012 Apr;12(2):87-93. Epub 2011 Dec 6. [http://www.clinical-breast-cancer.com/article/S1526-8209(11)00206-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22154117 PubMed]
 
−
 
 
−
==CMF {{#subobject:9c9c1d|Regimen=1}}==
 
−
 
 
−
CMF: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
−
===Regimen variant #1, 600/40/600 {{#subobject:4a66d3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1988.6.9.1377 Tannock et al. 1988]
 
−
|1981-1986
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMF_2|CMF]]; lower-dose
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19940501)73:9%3C2337::AID-CNCR2820730916%3E3.0.CO;2-Q Ingle et al. 1994 (NCCTG 87-32-52)]
 
−
|1987-1991
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#DES-CEF_88|DES-CEF]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #2, 1400/80/1000 {{#subobject:d3cef4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1987.5.10.1523 Aisner et al. 1987]
 
−
|rowspan=2|1976-1980
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#FAC_3|CAF]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|2. [[Breast_cancer_-_historical#CAFVP|CAFVP]]
 
−
| style="background-color:#d73027" |Inferior ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #3, 1400/60/800 {{#subobject:4a44d3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197611)38:5%3C1882::AID-CNCR2820380503%3E3.0.CO;2-H Canellos et al. 1976]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_historical#Melphalan_monotherapy_2|Melphalan]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
''Note: this was the dose used for patients older than 60 in the revised protocol of Canellos et al. 1976.''
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #4, 1400/80/1200 {{#subobject:4a77d3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639498/ Brambilla et al. 1976]
 
−
|1973-1974
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#Doxorubicin_.26_Vincristine_.28AV.29_99|AV]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197611)38:5%3C1882::AID-CNCR2820380503%3E3.0.CO;2-H Canellos et al. 1976]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_historical#Melphalan_monotherapy_2|Melphalan]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J Bull et al. 1978]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FAC_3|CAF]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19821001)50:7%3C1235::AID-CNCR2820500703%3E3.0.CO;2-L Tormey et al. 1982 (ECOG E2173)]
 
−
|1973-1974
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|1. [[#Doxorubicin_.26_Vincristine_.28AV.29_99|AV]]<br>2. [[Breast_cancer_-_historical#CMFP_2|CMFP]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19851215)56:12%3C2745::AID-CNCR2820561204%3E3.0.CO;2-G Viladiu et al. 1985]
 
−
|1978-1981
 
−
|style="background-color:#1a9851" |Randomized (C)
 
−
|1. [[#CMFT_2|CMFT]]<br> 2. [[#CMF_.26_MPA_88|CMF & MPA]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior ORR
 
−
|-
 
−
|[https://www.ejcancer.com/article/0277-5379(91)90259-G Engelsman et al. 1991 (EORTC 10808)]
 
−
|1981-1984
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMF_2|CMF]]; 600/40/600 (IV)
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a057671 Cocconi et al. 1990]
 
−
|1981-1985
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#CMF_2|CMF]] x 6, then intensification
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of TTP/OS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(05)80296-5/pdf Yosef et al. 1993]
 
−
|1983-1987
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#SMF_99|SMF]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of TTF/OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1991.9.4.664 Cocconi et al. 1991]
 
−
|1985-1988
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#Cisplatin_.26_Etoposide_.28EP.29_88|PE]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2001.19.4.943 Ackland et al. 2001 (HEPI 013)]
 
−
|1990-1992
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_3|CEF]]
 
−
| style="background-color:#d73027" |Inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM200004133421501 Stadtmauer et al. 2000]
 
−
|1990-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMF_2|CMF]] x 4-6, then [[Breast_cancer_-_historical#CTCb.2C_then_auto_HSCT_2|HDT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://insights.ovid.com/pubmed?pmid=16096436 von Minckwitz et al. 2005]
 
−
|1996-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#BMF_88|BMF]]
 
−
| style="background-color:#d73027" |Inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2010.33.9101 Stockler et al. 2011 (ANZ 0001)]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_monotherapy_2|Capecitabine]]; continuous<br> 2. [[#Capecitabine_monotherapy_2|Capecitabine]]; intermittent
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
''Note: this was the dose used for patients younger than 60 in the revised protocol of Canellos et al. 1976.''
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #5, 1400/120/1200 {{#subobject:5b33d3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197611)38:5%3C1882::AID-CNCR2820380503%3E3.0.CO;2-H Canellos et al. 1976]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_historical#Melphalan_monotherapy_2|Melphalan]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
''Note: this was the dose used for patients in the original protocol of Canellos et al. 1976 and was deemed too myelotoxic.''
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
*[[Methotrexate (MTX)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# Brambilla C, De Lena M, Rossi A, Valagussa P, Bonadonna G. Response and survival in advanced breast cancer after two non-cross-resistant combinations. Br Med J. 1976 Apr 3;1(6013):801-4. [https://doi.org/10.1136/bmj.1.6013.801 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639498/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/1260337 PubMed]
 
−
# Canellos GP, Pocock SJ, Taylor SG 3rd, Sears ME, Klaasen DJ, Band PR; [[Study_Groups#ECOG|ECOG]]. Combination chemotherapy for metastatic breast carcinoma: prospective comparison of multiple drug therapy with L-phenylalanine mustard. Cancer. 1976 Nov;38(5):1882-6. [https://doi.org/10.1002/1097-0142(197611)38:5%3C1882::AID-CNCR2820380503%3E3.0.CO;2-H link to original article] [https://pubmed.ncbi.nlm.nih.gov/991103 PubMed]
 
−
# Bull JM, Tormey DC, Li SH, Carbone PP, Falkson G, Blom J, Perlin E, Simon R. A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer. 1978 May;41(5):1649-57. [https://doi.org/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J link to original article] [https://pubmed.ncbi.nlm.nih.gov/348293 PubMed]
 
−
# '''ECOG E2173:''' Tormey DC, Gelman R, Band PR, Sears M, Rosenthal SN, DeWys W, Perlia C, Rice MA. Comparison of induction chemotherapies for metastatic breast cancer: an Eastern Cooperative Oncology Group Trial. Cancer. 1982 Oct 1;50(7):1235-44. [https://doi.org/10.1002/1097-0142(19821001)50:7%3C1235::AID-CNCR2820500703%3E3.0.CO;2-L link to original article] [https://pubmed.ncbi.nlm.nih.gov/7049347 PubMed]
 
−
# Viladiu P, Alonso MC, Avella A, Beltrán M, Borrás J, Ojeda B, Bosch FX. Chemotherapy versus chemotherapy plus hormonotherapy in postmenopausal advanced breast cancer patients: a randomized trial. Cancer. 1985 Dec 15;56(12):2745-50. [https://doi.org/10.1002/1097-0142(19851215)56:12%3C2745::AID-CNCR2820561204%3E3.0.CO;2-G link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3902200 PubMed]
 
−
# Aisner J, Weinberg V, Perloff M, Weiss R, Perry M, Korzun A, Ginsberg S, Holland JF; [[Study_Groups#CALGB|CALGB]]. Chemotherapy versus chemoimmunotherapy (CAF v CAFVP v CMF each +/- MER) for metastatic carcinoma of the breast: a CALGB study. J Clin Oncol. 1987 Oct;5(10):1523-33. [https://doi.org/10.1200/JCO.1987.5.10.1523 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3655855 PubMed]
 
−
# Tannock IF, Boyd NF, DeBoer G, Erlichman C, Fine S, Larocque G, Mayers C, Perrault D, Sutherland H. A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer. J Clin Oncol. 1988 Sep;6(9):1377-87. [https://doi.org/10.1200/JCO.1988.6.9.1377 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2458438 PubMed]
 
−
# Cocconi G, Bisagni G, Bacchi M, Buzzi F, Canaletti R, Carpi A, Ceci G, Colozza A, De Lisi V, Lottici R, Passalacqua R, Peracchia G; GOIRC. A comparison of continuation versus late intensification followed by discontinuation of chemotherapy in advanced breast cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research (GOIRC). Ann Oncol. 1990;1(1):36-44. [https://doi.org/10.1093/oxfordjournals.annonc.a057671 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2078484 PubMed]
 
−
# '''EORTC 10808:''' Engelsman E, Klijn JC, Rubens RD, Wildiers J, Beex LV, Nooij MA, Rotmensz N, Sylvester R. "Classical" CMF versus a 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer: an EORTC Breast Cancer Co-operative Group Phase III Trial (10808). Eur J Cancer. 1991;27(8):966-70. [https://www.ejcancer.com/article/0277-5379(91)90259-G link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1832904 PubMed]
 
−
# Cocconi G, Bisagni G, Bacchi M, Boni C, Bartolucci R, Ceci G, Colozza MA, De Lisi V, Lottici R, Mosconi AM, Passalacqua R, Tonato M; Italian Oncology Group for Clinical Research. Cisplatin and etoposide as first-line chemotherapy for metastatic breast carcinoma: a prospective randomized trial of the Italian Oncology Group for Clinical Research. J Clin Oncol. 1991 Apr;9(4):664-9. [https://doi.org/10.1200/JCO.1991.9.4.664 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2066763 PubMed]
 
−
# Yosef H, Slater A, Keen CW, Bunting JS, Hope-Stone H, Parmar H, Roberts JT, Termander B, Nilsson B. Prednimustine (Sterecyt) versus cyclophosphamide both in combination with methotrexate and 5-fluorouracil in the treatment of advanced breast cancer. Eur J Cancer. 1993;29A(8):1100-5. [https://www.ejcancer.com/article/S0959-8049(05)80296-5/pdf link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8518020 PubMed]
 
−
# '''NCCTG 87-32-52:''' Ingle JN, Foley JF, Mailliard JA, Krook JE, Hartmann LC, Jung SH, Veeder MH, Gesme DH Jr, Hatfield AK, Goldberg RM. Randomized trial of cyclophosphamide, methotrexate, and 5-fluorouracil with or without estrogenic recruitment in women with metastatic breast cancer. Cancer. 1994 May 1;73(9):2337-43. [https://doi.org/10.1002/1097-0142(19940501)73:9%3C2337::AID-CNCR2820730916%3E3.0.CO;2-Q link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8168039 PubMed]
 
−
# Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK, Sickles C, Glick JH; Philadelphia Bone Marrow Transplant Group. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med. 2000 Apr 13;342(15):1069-76. [https://doi.org/10.1056/NEJM200004133421501 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10760307 PubMed]
 
−
# '''HEPI 013:''' Ackland SP, Anton A, Breitbach GP, Colajori E, Tursi JM, Delfino C, Efremidis A, Ezzat A, Fittipaldo A, Kolaric K, Lopez M, Viaro D; HEPI 013 study group. Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study. J Clin Oncol. 2001 Feb 15;19(4):943-53. [https://doi.org/10.1200/jco.2001.19.4.943 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11181656 PubMed]
 
−
# von Minckwitz G, Chernozemsky I, Sirakova L, Chilingirov P, Souchon R, Marschner N, Kleeberg U, Tsekov C, Fritze D, Thomssen C, Stuart N, Vermorken JB, Loibl S, Merkle Kh, Kaufmann M. Bendamustine prolongs progression-free survival in metastatic breast cancer (MBC): a phase III prospective, randomized, multicenter trial of bendamustine hydrochloride, methotrexate and 5-fluorouracil (BMF) versus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as first-line treatment of MBC. Anticancer Drugs. 2005 Sep;16(8):871-7. [https://insights.ovid.com/pubmed?pmid=16096436 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16096436 PubMed]
 
−
<!-- Presented in part at the 29th Annual San Antonio Breast Cancer Symposium, December 14-17, 2006, San Antonio, TX, and 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL. -->
 
−
# '''ANZ 0001:''' Stockler MR, Harvey VJ, Francis PA, Byrne MJ, Ackland SP, Fitzharris B, Van Hazel G, Wilcken NR, Grimison PS, Nowak AK, Gainford MC, Fong A, Paksec L, Sourjina T, Zannino D, Gebski V, Simes RJ, Forbes JF, Coates AS. Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4498-504. Epub 2011 Oct 24. [https://doi.org/10.1200/jco.2010.33.9101 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22025143 PubMed]
 
−
 
 
−
==CMFT {{#subobject:9c9c1d|Regimen=1}}==
 
−
 
 
−
CMFT: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>T</u>'''amoxifen
 
−
===Regimen {{#subobject:ab14d5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19830215)51:4%3C581::AID-CNCR2820510404%3E3.0.CO;2-G Cocconi et al. 1983]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|[[#CMF_2|CMF]]
 
−
| style="background-color:#d9ef8b" |Might have superior TTF
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19851215)56:12%3C2745::AID-CNCR2820561204%3E3.0.CO;2-G Viladiu et al. 1985]
 
−
|1978-1981
 
−
|style="background-color:#1a9851" |Randomized (E-esc)
 
−
|1. [[#CMF_2|CMF]]<br> 2. [[#CMF_.26_MPA_99|CMF & MPA]]
 
−
| style="background-color:#91cf60" |Seems to have superior ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]]
 
−
===References===
 
−
# Cocconi G, De Lisi V, Boni C, Mori P, Malacarne P, Amadori D, Giovanelli E. Chemotherapy versus combination of chemotherapy and endocrine therapy in advanced breast cancer: a prospective randomized study. Cancer. 1983 Feb 15;51(4):581-8. [https://doi.org/10.1002/1097-0142(19830215)51:4%3C581::AID-CNCR2820510404%3E3.0.CO;2-G link to original article] [https://pubmed.ncbi.nlm.nih.gov/6336981 PubMed]
 
−
# Viladiu P, Alonso MC, Avella A, Beltrán M, Borrás J, Ojeda B, Bosch FX. Chemotherapy versus chemotherapy plus hormonotherapy in postmenopausal advanced breast cancer patients: a randomized trial. Cancer. 1985 Dec 15;56(12):2745-50. [https://doi.org/10.1002/1097-0142(19851215)56:12%3C2745::AID-CNCR2820561204%3E3.0.CO;2-G link to original article] [https://pubmed.ncbi.nlm.nih.gov/3902200 PubMed]
 
−
 
 
−
==Docetaxel monotherapy {{#subobject:47db8e|Regimen=1}}==
 
−
 
 
−
D: '''<u>D</u>'''ocetaxel
 
−
<br>T: '''<u>T</u>'''axotere (Docetaxel)
 
−
===Regimen variant #1, 30 mg/m<sup>2</sup> 3 weeks out of 4 {{#subobject:09ffcd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://www.karger.com/Article/FullText/320640 Stemmler et al. 2011 (D2)]
 
−
|2001-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Docetaxel_monotherapy_2|Docetaxel]]; q3wk
 
−
| style="background-color:#fc8d59" |Seems to have inferior ORR
 
−
| style="background-color:#1a9850" |Superior hematotoxicity
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #2, 40 mg/m<sup>2</sup> 3 weeks out of 4 {{#subobject:09eecd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.23321 Rivera et al. 2008]
 
−
|2001-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Docetaxel_monotherapy_2|Docetaxel]]; q3wk
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
| style="background-color:#1a9850" |Superior toxicity
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycle 1: 35 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 
−
**Cycle 2 onwards: 40 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #3, 40 mg/m<sup>2</sup> 6 weeks out of 8 {{#subobject:6ed28b|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2000.18.6.1212 Burstein et al. 2000]
 
−
|1998
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
 
−
 
 
−
'''8-week cycles'''
 
−
 
 
−
===Regimen variant #4, 60 mg/m<sup>2</sup> q3wk {{#subobject:cf6000|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdn781 Katsumata et al. 2009 (JCOG9802)]
 
−
|1999-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_3|AC]]<br> 2. [[#AC.2FD_99|AC/D]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00411-8 Takashima et al. 2015 (SELECT BC)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#S-1_monotherapy|S-1]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior OS
 
−
| style="background-color:#d73027" |Inferior EQ-5D score
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 6 cycles'''
 
−
 
 
−
===Regimen variant #5, 60 mg/m<sup>2</sup> q4wk {{#subobject:c5cf8d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00411-8 Takashima et al. 2015 (SELECT BC)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#S-1_monotherapy|S-1]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior OS
 
−
| style="background-color:#d73027" |Inferior EQ-5D score
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #6, 75 mg/m<sup>2</sup> q3wk {{#subobject:32c5e5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://www.karger.com/Article/FullText/320640 Stemmler et al. 2011 (D2)]
 
−
|2001-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_monotherapy_2|Docetaxel]]; weekly
 
−
| style="background-color:#91cf60" |Seems to have superior ORR
 
−
| style="background-color:#d73027" |Inferior hematotoxicity
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2008.20.5013 Sparano et al. 2009 (DOXIL-BCA-3001)]
 
−
|2004-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Pegylated_liposomal_doxorubicin_88|Docetaxel & PLD]]
 
−
| style="background-color:#d73027" |Inferior TTP
 
−
| style="background-color:#1a9850" |Less toxic
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00411-8 Takashima et al. 2015 (SELECT BC)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#S-1_monotherapy|S-1]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior OS
 
−
| style="background-color:#d73027" |Inferior EQ-5D score
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2014.57.1513 Mackey et al. 2014 (ROSE/TRIO-12)]
 
−
|2008-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Ramucirumab_88|Docetaxel & Ramucirumab]]
 
−
| style="background-color:#fee08b" |Might have inferior PFS
 
−
|
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #7, 75 mg/m<sup>2</sup> q4wk {{#subobject:79ac92|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00411-8 Takashima et al. 2015 (SELECT BC)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#S-1_monotherapy|S-1]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior OS
 
−
| style="background-color:#d73027" |Inferior EQ-5D score
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #8, 100 mg/m<sup>2</sup> x 6 {{#subobject:79aj8c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361414/ Pacilio et al. 2006]
 
−
|2000-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Epirubicin_.28DE.29_99|Docetaxel & Epirubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #9, 100 mg/m<sup>2</sup> x 8 {{#subobject:fajga1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.11.8851 Crump et al. 2007 (NCIC-CTG MA.16)]
 
−
|1997-2000
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#FAC_3|FAC]] x 4, then HDCT with auto HSCT<br> 2. [[#FEC_3|FEC]] x 4, then HDCT with auto HSCT<br> 3. [[#Paclitaxel_monotherapy_99|Paclitaxel]] x 4, , then HDCT with auto HSCT<br> 4. [[#Docetaxel_monotherapy_2|Docetaxel]] x 4, then HDCT with auto HSCT
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===Regimen variant #10, 100 mg/m<sup>2</sup> x 9 {{#subobject:fa8j8c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.2008.21.6457 Miles et al. 2010 (AVADO)]
 
−
|rowspan=2|2006-2007
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]]; 100/7.5
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|2. [[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]]; 100/15
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 9 cycles'''
 
−
 
 
−
===Regimen variant #11, 100 mg/m<sup>2</sup>, indefinite {{#subobject:bf6578|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.2.422 Trudeau et al. 1996]
 
−
|1992-1993
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.23321 Rivera et al. 2008]
 
−
|2001-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_monotherapy_2|Docetaxel]]; weekly
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
| style="background-color:#d73027" |Inferior toxicity
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.33.9507 Nielsen et al. 2011]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Gemcitabine|Docetaxel & Gemcitabine]]
 
−
| style="background-color:#fee08b" |Might have inferior TTP
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860103/ Joensuu et al. 2009 (B9E-MC-S241)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#D.2FG_99|D/G]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 
−
| style="background-color:#d73027" |More toxic
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2008.18.5397 Gradishar et al. 2009]
 
−
|2005-2006
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|1. [[#nab-Paclitaxel_monotherapy_2|nab-Paclitaxel]]; higher-dose weekly<br> 2. [[#nab-Paclitaxel_monotherapy_2|nab-Paclitaxel]]; lower-dose weekly<br> 3. [[#nab-Paclitaxel_monotherapy_2|nab-Paclitaxel]]; q3wk
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2011.35.7376 Bergh et al. 2012 (SUN 1064)]
 
−
|2007-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Sunitinib_99|Docetaxel & Sunitinib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
**Note: Rivera et al. 2008 gave 75 mg/m<sup>2</sup> in cycle 1, with escalation to 100 mg/m<sup>2</sup> depending on toxicity
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# Trudeau ME, Eisenhauer EA, Higgins BP, Letendre F, Lofters WS, Norris BD, Vandenberg TA, Delorme F, Muldal AM; National Cancer Institute of Canada-Clinical Trials Group. Docetaxel in patients with metastatic breast cancer: a phase II study of the National Cancer Institute of Canada-Clinical Trials Group. J Clin Oncol. 1996 Feb;14(2):422-8. [https://doi.org/10.1200/JCO.1996.14.2.422 link to original article] '''contains dosing details in abstract'''  [https://pubmed.ncbi.nlm.nih.gov/8636752 PubMed]
 
−
# '''Review:''' Burris HA 3rd. Single-agent docetaxel (Taxotere) in randomized phase III trials. Semin Oncol. 1999 Jun;26(3 Suppl 9):1-6. [https://pubmed.ncbi.nlm.nih.gov/10426452 PubMed]
 
−
# Burstein HJ, Manola J, Younger J, Parker LM, Bunnell CA, Scheib R, Matulonis UA, Garber JE, Clarke KD, Shulman LN, Winer EP. Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol. 2000 Mar;18(6):1212-9. [https://doi.org/10.1200/jco.2000.18.6.1212 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10715290 PubMed] content property of [http://hemonc.org HemOnc.org]
 
−
# Pacilio C, Morabito A, Nuzzo F, Gravina A, Labonia V, Landi G, Rossi E, De Maio E, Di Maio M, D'Aiuto G, Botti G, Normanno N, Chiodini P, Gallo C, Perrone F, de Matteis A; NCI-Naples Breast Cancer Group. Is epirubicin effective in first-line chemotherapy of metastatic breast cancer (MBC) after an epirubicin-containing adjuvant treatment? A single centre phase III trial. Br J Cancer. 2006 May 8;94(9):1233-6. [https://www.nature.com/articles/6603096 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361414/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16622454 PubMed]
 
−
#'''NCIC-CTG MA.16:''' Crump M, Gluck S, Tu D, Stewart D, Levine M, Kirkbride P, Dancey J, O'Reilly S, Shore T, Couban S, Girouard C, Marlin S, Shepherd L, Pritchard KI. Randomized trial of high-dose chemotherapy with autologous peripheral-blood stem-cell support compared with standard-dose chemotherapy in women with metastatic breast cancer: NCIC MA.16. J Clin Oncol. 2008 Jan 1;26(1):37-43. Epub 2007 Nov 19. [https://doi.org/10.1200/jco.2007.11.8851 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18025439/ PubMed] NCT00003032
 
−
# Rivera E, Mejia JA, Arun BK, Adinin RB, Walters RS, Brewster A, Broglio KR, Yin G, Esmaeli B, Hortobagyi GN, Valero V. Phase 3 study comparing the use of docetaxel on an every-3-week versus weekly schedule in the treatment of metastatic breast cancer. Cancer. 2008 Apr 1;112(7):1455-61. [https://doi.org/full/10.1002/cncr.23321 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18300256 PubMed]
 
−
# '''JCOG9802:''' Katsumata N, Watanabe T, Minami H, Aogi K, Tabei T, Sano M, Masuda N, Andoh J, Ikeda T, Shibata T, Takashima S. Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel, and alternating AC and docetaxel as front-line chemotherapy for metastatic breast cancer: Japan Clinical Oncology Group trial (JCOG9802). Ann Oncol. 2009 Jul;20(7):1210-5. Epub 2009 Mar 2. [https://doi.org/10.1093/annonc/mdn781 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19254942 PubMed]
 
−
<!-- Presented in part at the 29th Annual San Antonio Breast Cancer Symposium, December 14-17, 2006, San Antonio, TX; the 43rd Annual Meeting of the American Society for Clinical Oncology, June 1-5, 2007, Chicago, IL; the 14th European Cancer Conference, September 23-27, 2007, Barcelona, Spain; and the 6th European Breast Cancer Conference, April 15-19, 2008, Berlin, Germany. -->
 
−
# Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009 Aug 1;27(22):3611-9. Epub 2009 May 26. Erratum in: J Clin Oncol. 2011 Jul 1;29(19):2739. [https://doi.org/10.1200/jco.2008.18.5397 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19470941 PubMed]
 
−
# '''DOXIL-BCA-3001:''' Sparano JA, Makhson AN, Semiglazov VF, Tjulandin SA, Balashova OI, Bondarenko IN, Bogdanova NV, Manikhas GM, Oliynychenko GP, Chatikhine VA, Zhuang SH, Xiu L, Yuan Z, Rackoff WR. Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. J Clin Oncol. 2009 Sep 20;27(27):4522-9. Epub 2009 Aug 17. [https://doi.org/10.1200/JCO.2008.20.5013 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19687336 PubMed] NCT00091442
 
−
# '''B9E-MC-S241:''' Joensuu H, Sailas L, Alanko T, Sunela K, Huuhtanen R, Utriainen M, Kokko R, Bono P, Wigren T, Pyrhönen S, Turpeenniemi-Hujanen T, Asola R, Leinonen M, Hahka-Kemppinen M, Kellokumpu-Lehtinen P. Docetaxel versus docetaxel alternating with gemcitabine as treatments of advanced breast cancer: final analysis of a randomised trial. Ann Oncol. 2010 May;21(5):968-73. Epub 2009 Oct 9. [https://doi.org/10.1093/annonc/mdp397 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860103/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19819914 PubMed] NCT00191243
 
−
# '''AVADO:''' Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3239-47. Epub 2010 May 24. [https://doi.org/10.1200/JCO.2008.21.6457 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20498403 PubMed] NCT00333775
 
−
# '''D2:''' Stemmler HJ, Harbeck N, Gröll de Rivera I, Vehling Kaiser U, Rauthe G, Abenhardt W, Artmann A, Sommer H, Meerpohl HG, Kiechle M, Heinemann V. Prospective multicenter randomized phase III study of weekly versus standard docetaxel (D2) for first-line treatment of metastatic breast cancer. Oncology. 2010;79(3-4):197-203. Epub 2011 Mar 1. [https://www.karger.com/Article/FullText/320640 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21358207 PubMed]
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
# Nielsen DL, Bjerre KD, Jakobsen EH, Cold S, Stenbygaard L, Sørensen PG, Kamby C, Møller S, Jørgensen CL, Andersson M; Danish Breast Cancer Cooperative Group. Gemcitabine plus docetaxel versus docetaxel in patients with predominantly human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: a randomized, phase III study by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2011 Dec 20;29(36):4748-54. Epub 2011 Nov 14. [https://doi.org/10.1200/JCO.2010.33.9507 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22084374 PubMed]
 
−
<!-- Presented, in part, at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL. -->
 
−
# '''SUN 1064:''' Bergh J, Bondarenko IM, Lichinitser MR, Liljegren A, Greil R, Voytko NL, Makhson AN, Cortes J, Lortholary A, Bischoff J, Chan A, Delaloge S, Huang X, Kern KA, Giorgetti C. First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study. J Clin Oncol. 2012 Mar 20;30(9):921-9. Epub 2012 Feb 13. [https://doi.org/10.1200/JCO.2011.35.7376 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22331954 PubMed] NCT00393939
 
−
# '''ROSE/TRIO-12:''' Mackey JR, Ramos-Vazquez M, Lipatov O, McCarthy N, Krasnozhon D, Semiglazov V, Manikhas A, Gelmon KA, Konecny GE, Webster M, Hegg R, Verma S, Gorbunova V, Abi Gerges D, Thireau F, Fung H, Simms L, Buyse M, Ibrahim A, Martín M. Primary results of ROSE/TRIO-12, a randomized placebo-controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer. J Clin Oncol. 2015 Jan 10;33(2):141-8. Epub 2014 Sep 2. [https://doi.org/10.1200/JCO.2014.57.1513 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25185099 PubMed] NCT00703326
 
−
# '''SELECT BC:''' Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. Epub 2015 Nov 27. [https://doi.org/10.1016/S1470-2045(15)00411-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26617202 PubMed] UMIN C000000416
 
−
## '''HRQoL analysis:''' Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Doihara H, Akabane H, Kashiwaba M, Watanabe T, Ohashi Y, Mukai H. Long-term health status as measured by EQ-5D among patients with metastatic breast cancer: comparison of first-line oral S-1 and taxane therapies in the randomized phase III SELECT BC trial. Qual Life Res. 2017 Feb;26(2):445-453. Epub 2016 Aug 12. [https://doi.org/10.1007/s11136-016-1388-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27517267 PubMed]
 
−
 
 
−
==Docetaxel & Bevacizumab {{#subobject:65222f|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, 75/15, indefinite {{#subobject:4040c4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Docetaxel_monotherapy_2|Docetaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS <br>(HR 0.64, 95% CI 0.52-0.80)
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-014-3217-y Lück et al. 2014 (TABEA)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Docetaxel_.28TX.29_.26_Bevacizumab_99|TX & Bevacizumab]]<br>2. [[#Capecitabine.2C_Paclitaxel.2C_Bevacizumab_99|Capecitabine, Paclitaxel, Bevacizumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdw077 Trédan et al. 2016 (GINECO-BR107)]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]], then [[#Exemestane_.26_Bevacizumab_99|Exemestane & Bevacizumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #2, 100/15, 9 cycles {{#subobject:48a438|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.2008.21.6457 Miles et al. 2010 (AVADO)]
 
−
|rowspan=2|2006-2007
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Docetaxel_monotherapy_2|Docetaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|-
 
−
|2. [[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]]; 100/7.5
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 9 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Bevacizumab_monotherapy_2|Bevacizumab]] maintenance
 
−
 
 
−
===Regimen variant #3, 100/15, indefinite {{#subobject:8bn438|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Docetaxel_monotherapy_2|Docetaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS <br>(HR 0.64, 95% CI 0.52-0.80)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
===References===
 
−
# '''AVADO:''' Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3239-47. Epub 2010 May 24. [https://doi.org/10.1200/JCO.2008.21.6457 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20498403 PubMed] NCT00333775
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
# '''TABEA:''' Lück HJ, Lübbe K, Reinisch M, Maass N, Feisel-Schwickardi G, Tomé O, Janni W, Aydogdu M, Neunhöffer T, Ober A, Aktas B, Park-Simon TW, Schumacher C, Höffkes HG, Illmer T, Wagner H, Mehta K, von Minckwitz G, Nekljudova V, Loibl S. Phase III study on efficacy of taxanes plus bevacizumab with or without capecitabine as first-line chemotherapy in metastatic breast cancer. Breast Cancer Res Treat. 2015 Jan;149(1):141-9. Epub 2014 Dec 18. [https://doi.org/10.1007/s10549-014-3217-y link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25519041 PubMed]
 
−
# '''GINECO-BR107:''' Trédan O, Follana P, Moullet I, Cropet C, Trager-Maury S, Dauba J, Lavau-Denes S, Diéras V, Béal-Ardisson D, Gouttebel M, Orfeuvre H, Stefani L, Jouannaud C, Bürki F, Petit T, Guardiola E, Becuwe C, Blot E, Pujade-Lauraine E, Bachelot T. A phase III trial of exemestane plus bevacizumab maintenance therapy in patients with metastatic breast cancer after first-line taxane and bevacizumab: a GINECO group study. Ann Oncol. 2016 Jun;27(6):1020-9. Epub 2016 Feb 24. [https://doi.org/10.1093/annonc/mdw077 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26916095 PubMed] NCT01303679
 
−
 
 
−
==Docetaxel & Doxorubicin (AT) {{#subobject:145802|Regimen=1}}==
 
−
 
 
−
AT: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>T</u>'''axotere (Docetaxel)
 
−
<br>AD: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>D</u>'''ocetaxel
 
−
===Regimen variant #1, 50/75 x 4 {{#subobject:9cca82|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-007-9651-3 Cassier et al. 2007 (ERASME 3)]
 
−
|2000-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Paclitaxel_.28AT.29_2|AT (Taxol)]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV over 15 minutes once on day 1, '''given first'''
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given second'''
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Docetaxel_monotherapy_2|Docetaxel]] x 4
 
−
 
 
−
===Regimen variant #2, 50/75 x 6 {{#subobject:9c6b82|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.06.236 Bontenbal et al. 2005]
 
−
|1997-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#FAC_3|FAC]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.08.125 Alba et al. 2004 (GEICAM-9903)]
 
−
|1999-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_monotherapy_2|A]], then [[#Docetaxel_monotherapy_2|T (Taxotere)]]
 
−
|
 
−
| style="background-color:#d73027" |More toxic
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #3, 50/75 x 8 {{#subobject:9cba382|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.04.040 Nabholtz et al. 2003 (TAX 306)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_3|AC]]
 
−
| style="background-color:#91cf60" |Seems to have superior TTP
 
−
|
 
−
|-
 
−
|[https://www.karger.com/Article/Abstract/320625 Stemmler et al. 2010 (D4)]
 
−
|2001-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Doxorubicin_.28AT.29|AT (Taxotere)]]; weekly docetaxel
 
−
| style="background-color:#ffffbf" |Did not meet secondary endpoint of TTP
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of hematotoxicity
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===References===
 
−
# '''TAX 306:''' Nabholtz JM, Falkson C, Campos D, Szanto J, Martín M, Chan S, Pienkowski T, Zaluski J, Pinter T, Krzakowski M, Vorobiof D, Leonard R, Kennedy I, Azli N, Murawsky M, Riva A, Pouillart P; TAX 306 Study Group. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol. 2003 Mar 15;21(6):968-75. [https://doi.org/10.1200/jco.2003.04.040 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12637459 PubMed]
 
−
# '''GEICAM-9903:''' Alba E, Martín M, Ramos M, Adrover E, Balil A, Jara C, Barnadas A, Fernández-Aramburo A, Sánchez-Rovira P, Amenedo M, Casado A; GEICAM. Multicenter randomized trial comparing sequential with concomitant administration of doxorubicin and docetaxel as first-line treatment of metastatic breast cancer: a Spanish Breast Cancer Research Group (GEICAM-9903) phase III study. J Clin Oncol. 2004 Jul 1;22(13):2587-93. [https://doi.org/10.1200/JCO.2004.08.125 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15226326 PubMed]
 
−
# Bontenbal M, Creemers GJ, Braun HJ, de Boer AC, Janssen JT, Leys RB, Ruit JB, Goey SH, van der Velden PC, Kerkhofs LG, Schothorst KL, Schmitz PI, Bokma HJ, Verweij J, Seynaeve C; Dutch Community Setting Trial for the Clinical Trial Group. Phase II to III study comparing doxorubicin and docetaxel with fluorouracil, doxorubicin, and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: results of a Dutch Community Setting Trial for the Clinical Trial Group of the Comprehensive Cancer Centre. J Clin Oncol. 2005 Oct 1;23(28):7081-8. [https://doi.org/10.1200/JCO.2005.06.236 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16192591 PubMed]
 
−
# '''ERASME 3:''' Cassier PA, Chabaud S, Trillet-Lenoir V, Peaud PY, Tigaud JD, Cure H, Orfeuvre H, Salles B, Martin C, Jacquin JP, Agostini C, Guastalla JP, Pérol D, Bachelot T. A phase-III trial of doxorubicin and docetaxel versus doxorubicin and paclitaxel in metastatic breast cancer: results of the ERASME 3 study. Breast Cancer Res Treat. 2008 May;109(2):343-50. Epub 2007 Jul 5. [https://doi.org/10.1007/s10549-007-9651-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17611792 PubMed]
 
−
# '''D4:''' Stemmler HJ, Harbeck N, Gröll de Rivera I, Vehling Kaiser U, Rauthe G, Abenhardt W, Artmann A, Sommer H, Meerpohl HG, Kiechle M, Heinemann V. Prospective multicenter randomized phase III study of weekly versus standard docetaxel plus doxorubicin (D4) for first-line treatment of metastatic breast cancer. Oncology. 2010;79(3-4):204-10. Epub 2011 Mar 1. [https://www.karger.com/Article/Abstract/320625 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21358208 PubMed]
 
−
 
 
−
==Docetaxel & Epirubicin (DE) {{#subobject:8039af|Regimen=1}}==
 
−
 
 
−
DE: '''<u>D</u>'''ocetaxel & '''<u>E</u>'''pirubicin
 
−
<br>ED: '''<u>E</u>'''pirubicin & '''<u>D</u>'''ocetaxel
 
−
<br>ET: '''<u>E</u>'''pirubicin & '''<u>T</u>'''axotere (Docetaxel)
 
−
===Regimen variant #1, 8 cycles {{#subobject:ab14d5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409942/ Bonneterre et al. 2004]
 
−
|1998-2000
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
 
−
|[[#FEC_3|FEC]]
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdp585 Blohmer et al. 2010]
 
−
|2000-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 8 cycles'''
 
−
 
 
−
===Regimen variant #2, indefinite {{#subobject:bu13d5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdp498 Mavroudis et al. 2009 (HORG CT/02.09)]
 
−
|2002-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_2|TX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# Bonneterre J, Dieras V, Tubiana-Hulin M, Bougnoux P, Bonneterre ME, Delozier T, Mayer F, Culine S, Dohoulou N, Bendahmane B. Phase II multicentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer. Br J Cancer. 2004 Oct 18;91(8):1466-71. [https://www.nature.com/articles/6602179 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409942/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15381937 PubMed]
 
−
# '''HORG CT/02.09:''' Mavroudis D, Papakotoulas P, Ardavanis A, Syrigos K, Kakolyris S, Ziras N, Kouroussis C, Malamos N, Polyzos A, Christophyllakis C, Kentepozidis N, Georgoulias V; Hellenic Oncology Research Group. Randomized phase III trial comparing docetaxel plus epirubicin versus docetaxel plus capecitabine as first-line treatment in women with advanced breast cancer. Ann Oncol. 2010 Jan;21(1):48-54. Epub 2009 Nov 11. [https://doi.org/10.1093/annonc/mdp498 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19906761 PubMed] NCT00429871
 
−
# Blohmer JU, Schmid P, Hilfrich J, Friese K, Kleine-Tebbe A, Koelbl H, Sommer H, Morack G, Wischnewsky MB, Lichtenegger W, Kuemmel S. Epirubicin and cyclophosphamide versus epirubicin and docetaxel as first-line therapy for women with metastatic breast cancer: final results of a randomised phase III trial. Ann Oncol. 2010 Jul;21(7):1430-5. Epub 2010 Jan 20. [https://doi.org/10.1093/annonc/mdp585 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20089562 PubMed]
 
−
 
 
−
==Docetaxel & Gemcitabine {{#subobject:031a92|Regimen=1}}==
 
−
 
 
−
GD: '''<u>G</u>'''emcitabine & '''<u>D</u>'''ocetaxel
 
−
<br>GDoc: '''<u>G</u>'''emcitabine & '''<u>Doc</u>'''etaxel
 
−
===Regimen {{#subobject:c95bcd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.33.9507 Nielsen et al. 2011]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Docetaxel_monotherapy_2|Docetaxel]]
 
−
| style="background-color:#d9ef8b" |Might have superior TTP
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1007/s10549-008-0047-9 Fountzilas et al. 2008]
 
−
|rowspan=2|2002-2006
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_88|Carboplatin & Paclitaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|2. [[#Paclitaxel_monotherapy.2C_weekly_2|Paclitaxel]]; weekly
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdq578 Seidman et al. 2010 (B9E-MC-S273)]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_2|TX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621657/ Del Mastro et al. 2013 (B9E-IT-S376)]
 
−
|2005-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Docetaxel_.26_Gemcitabine|GD]]; weekly<br> 2. [[#Gemcitabine_.26_Paclitaxel|GT]]; q3wk<br> 3. [[#Gemcitabine_.26_Paclitaxel|GT]]; weekly
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
**Nielsen et al. 2011 gave docetaxel on day 8
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
====Subsequent treatment====
 
−
*B9E-MC-S273, upon progression: [[#Capecitabine_monotherapy_3|Capecitabine]]
 
−
 
 
−
===References===
 
−
# Fountzilas G, Dafni U, Dimopoulos MA, Koutras A, Skarlos D, Papakostas P, Gogas H, Bafaloukos D, Kalogera-Fountzila A, Samantas E, Briasoulis E, Pectasides D, Maniadakis N, Matsiakou F, Aravantinos G, Papadimitriou C, Karina M, Christodoulou C, Kosmidis P, Kalofonos HP; Hellenic Cooperative Oncology Group. A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer: a Hellenic Cooperative Oncology Group study. Breast Cancer Res Treat. 2009 May;115(1):87-99. Epub 2008 May 16. [https://doi.org/10.1007/s10549-008-0047-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18483853 PubMed]
 
−
# '''B9E-MC-S273:''' Seidman AD, Brufsky A, Ansari RH, Hart LL, Stein RS, Schwartzberg LS, Stewart JF, Russell CA, Chen SC, Fein LE, De La Cruz Vargas JA, Kim SB, Cavalheiro J, Zhao L, Gill JF, Obasaju CK, Orlando M, Tai DF. Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel with planned crossover to the alternate single agent in metastatic breast cancer. Ann Oncol. 2011 May;22(5):1094-101. Epub 2010 Nov 17. [https://doi.org/10.1093/annonc/mdq578 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21084429 PubMed] NCT00191438
 
−
## '''Pooled update:''' Seidman AD, Chan S, Wang J, Zhu C, Xu C, Xu B. A pooled analysis of gemcitabine plus docetaxel versus capecitabine plus docetaxel in metastatic breast cancer. Oncologist. 2014 May;19(5):443-52. Epub 2014 Apr 4. [https://doi.org/10.1634/theoncologist.2013-0428 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4012969/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24705980/ PubMed]
 
−
# Nielsen DL, Bjerre KD, Jakobsen EH, Cold S, Stenbygaard L, Sørensen PG, Kamby C, Møller S, Jørgensen CL, Andersson M; Danish Breast Cancer Cooperative Group. Gemcitabine plus docetaxel versus docetaxel in patients with predominantly human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: a randomized, phase III study by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2011 Dec 20;29(36):4748-54. Epub 2011 Nov 14. [https://doi.org/10.1200/JCO.2010.33.9507 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22084374 PubMed]
 
−
# '''B9E-IT-S376:''' Del Mastro L, Fabi A, Mansutti M, De Laurentiis M, Durando A, Merlo DF, Bruzzi P, La Torre I, Ceccarelli M, Kazeem G, Marchi P, Boy D, Venturini M, De Placido S, Cognetti F. Randomised phase 3 open-label trial of first-line treatment with gemcitabine in association with docetaxel or paclitaxel in women with metastatic breast cancer: a comparison of different schedules and treatments. BMC Cancer. 2013 Mar 28;13:164. [https://doi.org/10.1186/1471-2407-13-164 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621657/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23537313 PubMed] NCT00236899
 
−
 
 
−
==Doxorubicin monotherapy {{#subobject:8a2b88|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, 20 mg/m<sup>2</sup> weekly {{#subobject:96cac2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/0277-5379(86)90075-1 Gundersen et al. 1986]
 
−
|1982-1983
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[Breast_cancer_-_historical#CAV|VAC]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1016/0277-5379(90)90255-r Gundersen et al. 1990]
 
−
|1984-1986
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_monotherapy_2|Epirubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of ORR/OS
 
−
|-
 
−
|[https://doi.org/10.1016/0959-8049(94)00213-o Gundersen et al. 1994]
 
−
|1987-1990
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#Doxorubicin_.26_MPA_88|Doxorubicin & MPA]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 20 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''7-day cycles'''
 
−
 
 
−
===Regimen variant #2, 60 mg/m<sup>2</sup> q3wk {{#subobject:cf8189|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197402)33:2%3C519::AID-CNCR2820330229%3E3.0.CO;2-X Gottlieb et al. 1974 (SWG02)]
 
−
|1972
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Lomustine_monotherapy_88|Lomustine]]<br>2. [[#Semustine_monotherapy_77|Semustine]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197607)38:1%3C13::AID-CNCR2820380104%3E3.0.CO;2-5 Hoogstraten et al. 1976]
 
−
|1972-1974
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer_-_historical_#CMFVP_2|CMFVP]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior ORR
 
−
|-
 
−
|[https://doi.org/10.1002/mpo.2950160505 Vaughn et al. 1988 (SWOG S8020)]
 
−
|1980-1982
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Etoposide_88|Doxorubicin & Etoposide]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1991.9.12.2148 Perez et al. 1991]
 
−
|1985-1988
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_monotherapy_2|Epirubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of ORR/OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.12.2385 Norris et al. 2000 (NCIC-CTG MA.8)]
 
−
|1992-1995
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Vinorelbine_.28NA.29_99|NA]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.2003.08.013 Sledge et al. 2003 (ECOG E1193)]
 
−
|rowspan=2|1993-1995
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Doxorubicin_.26_Paclitaxel_.28AT.29_2|AT (Taxol)]]
 
−
| style="background-color:#d73027" |Inferior TTF
 
−
|-
 
−
|2. [[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdh097 O'Brien et al. 2004]
 
−
|1998-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Pegylated_liposomal_doxorubicin_monotherapy|PLD]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior PFS
 
−
|-
 
−
|}
 
−
''Note: in NCIC-CTG MA.8, this dose was after a mid-protocol amendment. Treatment in NCIC-CTG MA.8 was given until a cumulative dose of 450 mg/m<sup>2</sup>.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles (see note)'''
 
−
 
 
−
===Regimen variant #3, 75 mg/m<sup>2</sup> q3wk {{#subobject:1982c0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.4.724 Paridaens et al. 2000 (EORTC 10923)]
 
−
|1993-1996
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 7 cycles'''
 
−
 
 
−
===References===
 
−
# '''SWG02:''' Gottlieb JA, Rivkin SE, Spigel SC, Hoogstraten B, O'Bryan RM, Delaney FC, Singhakowinta A; [[Study_Groups#SWOG|SWOG]]. Proceedings: Superiority of adriamycin over oral nitrosoureas in patients with advanced breast carcinoma: a Southwest Cancer Chemotherapy study Group study. Cancer. 1974 Feb;33(2):519-26. [https://doi.org/10.1002/1097-0142(197402)33:2%3C519::AID-CNCR2820330229%3E3.0.CO;2-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/4812769 PubMed]
 
−
# Hoogstraten B, George SL, Samal B, Rivkin SE, Costanzi JJ, Bonnet JD, Thigpen T, Braine H; [[Study_Groups#SWOG|SWOG]]. Combination chemotherapy and adriamycin in patients with advanced breast cancer: a Southwest Oncology Group study. Cancer. 1976 Jul;38(1):13-20. [https://doi.org/10.1002/1097-0142(197607)38:1%3C13::AID-CNCR2820380104%3E3.0.CO;2-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/947510 PubMed]
 
−
# Gundersen S, Kvinnsland S, Klepp O, Kvaløy S, Lund E, Høst H. Weekly adriamycin versus VAC in advanced breast cancer: a randomized trial. Eur J Cancer Clin Oncol. 1986 Dec;22(12):1431-4. [https://doi.org/10.1016/0277-5379(86)90075-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3595668 PubMed]
 
−
# '''SWOG S8020:''' Vaughn CB, Green SJ, O'Bryan R, Reed M, Grozea PN, Fletcher WS, Green JB, Metch B, Oishi N. VP-16 + adriamycin vs adriamycin alone in advanced adenocarcinoma of the breast, phase II, a randomized trial: a Southwest Oncology Group Study. Med Pediatr Oncol. 1988;16(5):312-9. [https://doi.org/10.1002/mpo.2950160505 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3054453 PubMed]
 
−
# Gundersen S, Kvinnsland S, Klepp O, Lund E, Høst H; Norwegian Breast Cancer Group. Weekly Adriamycin vs 4-epidoxorubicin every second week in advanced breast cancer: a randomized trial. Eur J Cancer. 1990 Jan;26(1):45-8. [https://doi.org/10.1016/0277-5379(90)90255-r link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2138477 PubMed]
 
−
# Perez DJ, Harvey VJ, Robinson BA, Atkinson CH, Dady PJ, Kirk AR, Evans BD, Chapman PJ. A randomized comparison of single-agent doxorubicin and epirubicin as first-line cytotoxic therapy in advanced breast cancer. J Clin Oncol. 1991 Dec;9(12):2148-52. [https://doi.org/10.1200/JCO.1991.9.12.2148 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1960557 PubMed]
 
−
# Gundersen S, Hannisdal E, Lundgren S, Wist E; Norwegian Breast Cancer Group. Weekly doxorubicin with or without high-dose medroxyprogesterone acetate in hormone-resistant advanced breast cancer: a randomised study. Eur J Cancer. 1994;30A(12):1775-8. [https://doi.org/10.1016/0959-8049(94)00213-o link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7880604 PubMed]
 
−
# '''EORTC 10923:''' Paridaens R, Biganzoli L, Bruning P, Klijn JG, Gamucci T, Houston S, Coleman R, Schachter J, Van Vreckem A, Sylvester R, Awada A, Wildiers J, Piccart M. Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organisation for Research and Treatment of Cancer Randomized Study with cross-over. J Clin Oncol. 2000 Feb;18(4):724-33. [https://doi.org/10.1200/JCO.2000.18.4.724 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10673513 PubMed]
 
−
## '''HRQoL analysis:''' Kramer JA, Curran D, Piccart M, de Haes JC, Bruning PF, Klijn JG, Bontenbal M, van Pottelsberghe C, Groenvold M, Paridaens R. Randomised trial of paclitaxel versus doxorubicin as first-line chemotherapy for advanced breast cancer: quality of life evaluation using the EORTC QLQ-C30 and the Rotterdam symptom checklist. Eur J Cancer. 2000 Aug;36(12):1488-97. [https://www.ejcancer.com/article/S0959-8049(00)00134-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10930796 PubMed]
 
−
# '''NCIC-CTG MA.8:''' Norris B, Pritchard KI, James K, Myles J, Bennett K, Marlin S, Skillings J, Findlay B, Vandenberg T, Goss P, Latreille J, Rudinskas L, Lofters W, Trudeau M, Osoba D, Rodgers A. Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group study MA8. J Clin Oncol. 2000 Jun;18(12):2385-94. [https://doi.org/10.1200/JCO.2000.18.12.2385 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10856098 PubMed]
 
−
# '''ECOG E1193:''' Sledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK, Wood WC. Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2003 Feb 15;21(4):588-92. [https://doi.org/10.1200/JCO.2003.08.013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12586793 PubMed]
 
−
# O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440-9. [https://doi.org/10.1093/annonc/mdh097 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14998846 PubMed]
 
−
 
 
−
==Doxorubicin & Paclitaxel (AT) {{#subobject:86ac2d|Regimen=1}}==
 
−
 
 
−
AT: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>T</u>'''axol (Paclitaxel)
 
−
===Regimen variant #1, 50/150 {{#subobject:bf9bd0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2003.08.013 Sledge et al. 2003 (ECOG E1193)]
 
−
|1993-1995
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Doxorubicin_monotherapy_2|Doxorubicin]]<br> 2. [[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]; q3wk
 
−
| style="background-color:#1a9850" |Superior TTF
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] as follows, '''given first''':
 
−
**Cycles 1 to 8: 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Paclitaxel (Taxol)]] 150 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1, '''given second, 3 hours after doxorubicin'''
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #2, 50/175 {{#subobject:9cfac2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-007-9651-3 Cassier et al. 2007 (ERASME 3)]
 
−
|2000-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Doxorubicin_.28AT.29|AT (Taxotere)]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV over 15 minutes once on day 1, '''given first'''
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second'''
 
−
 
 
−
'''21-day cycle for 4 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]] x 4
 
−
 
 
−
===Regimen variant #3, 50/220 {{#subobject:adad22|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.6.1707 Jassem et al. 2001]
 
−
|1996-1998
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#FAC_3|FAC]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 23 vs 18.3 mo
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2009 update.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Paclitaxel (Taxol)]] 220 mg/m<sup>2</sup> IV over 3 hours once on day 2
 
−
 
 
−
'''21-day cycle for up to 8 cycles'''
 
−
 
 
−
===Regimen variant #4, 60/200 {{#subobject:91549a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2002.11.005 Biganzoli et al. 2002 (EORTC 10961)]
 
−
|1996-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_3|AC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.06.072 Schmid et al. 2005]
 
−
|1998-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Tandem auto HSCT
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|}
 
−
''Note: in EORTC 10961, first cycle of paclitaxel was 175 mg/m<sup>2</sup>.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV over 15 minutes once on day 1
 
−
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
 
−
'''21-day cycle for up to 6 cycles'''
 
−
 
 
−
===Regimen variant #5, with range {{#subobject:1f6e13|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1995.13.11.2688 Gianni et al. 1995]
 
−
|1993-1994
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Paclitaxel (Taxol)]] 125 to 200 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# Gianni L, Munzone E, Capri G, Fulfaro F, Tarenzi E, Villani F, Spreafico C, Laffranchi A, Caraceni A, Martini C, Stefanelli M, Valagussa P, Bonadonna G. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol. 1995 Nov;13(11):2688-99. [https://doi.org/10.1200/jco.1995.13.11.2688 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7595726 PubMed]
 
−
# Jassem J, Pieńkowski T, Płuzańska A, Jelic S, Gorbunova V, Mrsic-Krmpotic Z, Berzins J, Nagykalnai T, Wigler N, Renard J, Munier S, Weil C; Central & Eastern Europe and Israel Pacitaxel Breast Cancer Study Group. Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial. J Clin Oncol. 2001 Mar 15;19(6):1707-15. [https://doi.org/10.1200/JCO.2001.19.6.1707 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11251000 PubMed]
 
−
##'''Update:''' Jassem J, Pienkowski T, Pluzanska A, Jelic S, Gorbunova V, Berzins J, Nagykalnai T, Biganzoli L, Aloe A, Astier L, Munier S. Doxorubicin and paclitaxel versus fluorouracil, doxorubicin and cyclophosphamide as first-line therapy for women with advanced breast cancer: long-term analysis of the previously published trial. Onkologie. 2009 Sep;32(8-9):468-72. Epub 2009 Jul 20. [https://doi.org/10.1159/000226210 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19745590/ PubMed]
 
−
# '''EORTC 10961:''' Biganzoli L, Cufer T, Bruning P, Coleman R, Duchateau L, Calvert AH, Gamucci T, Twelves C, Fargeot P, Epelbaum R, Lohrisch C, Piccart MJ. Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: The European Organisation for Research and Treatment of Cancer 10961 multicenter phase III trial. J Clin Oncol. 2002 Jul 15;20(14):3114-21. [https://doi.org/10.1200/JCO.2002.11.005 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12118025 PubMed]
 
−
# '''ECOG E1193:''' Sledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK, Wood WC. Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2003 Feb 15;21(4):588-92. [https://doi.org/10.1200/JCO.2003.08.013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12586793 PubMed]
 
−
# Schmid P, Schippinger W, Nitsch T, Huebner G, Heilmann V, Schultze W, Hausmaninger H, Wischnewsky M, Possinger K. Up-front tandem high-dose chemotherapy compared with standard chemotherapy with doxorubicin and paclitaxel in metastatic breast cancer: results of a randomized trial. J Clin Oncol. 2005 Jan 20;23(3):432-40. [https://doi.org/10.1200/JCO.2005.06.072 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15659490 PubMed]
 
−
# '''ERASME 3:''' Cassier PA, Chabaud S, Trillet-Lenoir V, Peaud PY, Tigaud JD, Cure H, Orfeuvre H, Salles B, Martin C, Jacquin JP, Agostini C, Guastalla JP, Pérol D, Bachelot T. A phase-III trial of doxorubicin and docetaxel versus doxorubicin and paclitaxel in metastatic breast cancer: results of the ERASME 3 study. Breast Cancer Res Treat. 2008 May;109(2):343-50. Epub 2007 Jul 5. [https://doi.org/10.1007/s10549-007-9651-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17611792 PubMed]
 
−
 
 
−
==Pegylated liposomal doxorubicin monotherapy {{#subobject:2b08a6|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, 45 mg/m<sup>2</sup> {{#subobject:c2baf3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433520/ Smorenburg et al. 2014 (OMEGA)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Capecitabine_monotherapy_2|Capecitabine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 45 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycle for 6 cycles'''
 
−
 
 
−
===Regimen variant #2, 50 mg/m<sup>2</sup> {{#subobject:6ebaf9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdh097 O'Brien et al. 2004]
 
−
|1998-2000
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Doxorubicin_monotherapy_2|Doxorubicin]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222915/ Harbeck et al. 2016 (PELICAN)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Capecitabine_monotherapy_2|Capecitabine]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 50 mg/m<sup>2</sup> IV over up to 60 minutes once on day 1
 
−
**If infusion reactions occurred, infusion could be given over up to 90 minutes
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440-9. [https://doi.org/10.1093/annonc/mdh097 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14998846 PubMed]
 
−
# '''OMEGA:''' Smorenburg CH, de Groot SM, van Leeuwen-Stok AE, Hamaker ME, Wymenga AN, de Graaf H, de Jongh FE, Braun JJ, Los M, Maartense E, van Tinteren H, Nortier JW, Seynaeve C; Dutch Breast Cancer Research Group. A randomized phase III study comparing pegylated liposomal doxorubicin with capecitabine as first-line chemotherapy in elderly patients with metastatic breast cancer: results of the OMEGA study of the Dutch Breast Cancer Research Group BOOG. Ann Oncol. 2014 Mar;25(3):599-605. Epub 2014 Feb 6. [https://doi.org/10.1093/annonc/mdt588 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433520/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24504445 PubMed] ISRCTN11114726
 
−
# '''PELICAN:''' Harbeck N, Saupe S, Jäger E, Schmidt M, Kreienberg R, Müller L, Otremba BJ, Waldenmaier D, Dorn J, Warm M, Scholz M, Untch M, de Wit M, Barinoff J, Lück HJ, Harter P, Augustin D, Harnett P, Beckmann MW, Al-Batran SE; PELICAN Investigators. A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. Breast Cancer Res Treat. 2017 Jan;161(1):63-72. Epub 2016 Oct 31. [https://doi.org/10.1007/s10549-016-4033-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222915/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27798749 PubMed] NCT00266799
 
−
 
 
−
==Cyclophosphamide & Epirubicin (EC) {{#subobject:b81844|Regimen=1}}==
 
−
 
 
−
EC: '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide
 
−
 
 
−
===Regimen variant #1, 75/600 {{#subobject:8466d6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdh393 Chan et al. 2004]
 
−
|1996-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Non-pegylated_liposomal_doxorubicin_.28MC.29|MC]]
 
−
| style="background-color:#d73027" |Inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.01.1817 Langley et al. 2005 (UKNCRI AB01)]
 
−
|1996-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_.26_Paclitaxel_.28EP.29_3|EP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 6 to 8 cycles'''
 
−
 
 
−
===Regimen variant #2, 90/600 {{#subobject:6079b8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdp585 Blohmer et al. 2010]
 
−
|2000-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Epirubicin_.28DE.29_2|ED]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 8 cycles'''
 
−
 
 
−
===Regimen variant #3, with range {{#subobject:21d6fa|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Epirubicin_.28EC.29_.26_Bevacizumab|EC & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 90 to 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 8 cycles'''
 
−
===References===
 
−
# Chan S, Davidson N, Juozaityte E, Erdkamp F, Pluzanska A, Azarnia N, Lee LW. Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer. Ann Oncol. 2004 Oct;15(10):1527-34. [https://doi.org/10.1093/annonc/mdh393 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15367414 PubMed]
 
−
<!-- Presented at the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12-15, 2001. -->
 
−
# '''UKNCRI AB01:''' Langley RE, Carmichael J, Jones AL, Cameron DA, Qian W, Uscinska B, Howell A, Parmar M. Phase III trial of epirubicin plus paclitaxel compared with epirubicin plus cyclophosphamide as first-line chemotherapy for metastatic breast cancer: United Kingdom National Cancer Research Institute trial AB01. J Clin Oncol. 2005 Nov 20;23(33):8322-30. [https://doi.org/10.1200/jco.2005.01.1817 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16293863 PubMed]
 
−
# Blohmer JU, Schmid P, Hilfrich J, Friese K, Kleine-Tebbe A, Koelbl H, Sommer H, Morack G, Wischnewsky MB, Lichtenegger W, Kuemmel S. Epirubicin and cyclophosphamide versus epirubicin and docetaxel as first-line therapy for women with metastatic breast cancer: final results of a randomised phase III trial. Ann Oncol. 2010 Jul;21(7):1430-5. Epub 2010 Jan 20. [https://doi.org/10.1093/annonc/mdp585 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20089562 PubMed]
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
 
 
−
==Cyclophosphamide & Epirubicin (EC) & Bevacizumab {{#subobject:3e6b59|Regimen=1}}==
 
−
 
 
−
EC & Bevacizumab: '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, Bevacizumab
 
−
===Regimen {{#subobject:56e1be|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]]
 
−
| style="background-color:#1a9850" |Superior PFS <br>(HR 0.64, 95% CI 0.52-0.80)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 90 to 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Bevacizumab_monotherapy_2|Bevacizumab]] maintenance, if no PD
 
−
 
 
−
===References===
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
 
 
−
==Epirubicin & Paclitaxel (EP) {{#subobject:e10567|Regimen=1}}==
 
−
 
 
−
EP: '''<u>E</u>'''pirubicin & '''<u>P</u>'''aclitaxel
 
−
<br>ET: '''<u>E</u>'''pirubicin & '''<u>T</u>'''axol (Paclitaxel)
 
−
===Regimen variant #1, 60/175 {{#subobject:1a480a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-013-2589-8 Lück et al. 2013]
 
−
|2002-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Paclitaxel_.28XP.29_99|XP]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 6 cycles'''
 
−
 
 
−
===Regimen variant #2, 75/175 {{#subobject:d6aabd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-011-1880-9 Hatschek et al. 2011 (TEX trial)]
 
−
|2002-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TEX_99|TEX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: the doses of this regimen were individually adjusted after cycle 1; see paper for details.''
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #3, 75/200 {{#subobject:f9fb8b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.01.1817 Langley et al. 2005 (UKNCRI AB01)]
 
−
|1996-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 6 cycles'''
 
−
 
 
−
===Regimen variant #4, 80/175 {{#subobject:2bee43|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdh395 Fountzilas et al. 2004]
 
−
|1999-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 80 mg/m<sup>2</sup> IV once on day 1, '''given second'''
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
 
−
 
 
−
'''21-day cycle for up to 6 cycles'''
 
−
 
 
−
===Regimen variant #5, 90/200 {{#subobject:cabbcf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.20400 Conte et al. 2004]
 
−
|1996-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_monotherapy_2|E]], then [[#Paclitaxel_monotherapy.2C_q3wk|P]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 cycles'''
 
−
 
 
−
===References===
 
−
# Conte PF, Guarneri V, Bruzzi P, Prochilo T, Salvadori B, Bolognesi A, Aldrighetti D, Venturini M, Rosso R, Mammoliti S, Carnino F, Giannessi P, Costantini M, Moyano A, Baldini E; GONO. Concomitant versus sequential administration of epirubicin and paclitaxel as first-line therapy in metastatic breast carcinoma: results for the Gruppo Oncologico Nord Ovest randomized trial. Cancer. 2004 Aug 15;101(4):704-12. [https://doi.org/full/10.1002/cncr.20400 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15305399 PubMed]
 
−
# Fountzilas G, Kalofonos HP, Dafni U, Papadimitriou C, Bafaloukos D, Papakostas P, Kalogera-Fountzila A, Gogas H, Aravantinos G, Moulopoulos LA, Economopoulos T, Pectasides D, Maniadakis N, Siafaka V, Briasoulis E, Christodoulou C, Tsavdaridis D, Makrantonakis P, Razis E, Kosmidis P, Skarlos D, Dimopoulos MA; Hellenic Cooperative Oncology Group. Paclitaxel and epirubicin versus paclitaxel and carboplatin as first-line chemotherapy in patients with advanced breast cancer: a phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol. 2004 Oct;15(10):1517-26. [https://doi.org/10.1093/annonc/mdh395 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15367413 PubMed]
 
−
<!-- Presented at the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12-15, 2001. -->
 
−
# '''UKNCRI AB01:''' Langley RE, Carmichael J, Jones AL, Cameron DA, Qian W, Uscinska B, Howell A, Parmar M. Phase III trial of epirubicin plus paclitaxel compared with epirubicin plus cyclophosphamide as first-line chemotherapy for metastatic breast cancer: United Kingdom National Cancer Research Institute trial AB01. J Clin Oncol. 2005 Nov 20;23(33):8322-30. [https://doi.org/10.1200/jco.2005.01.1817 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16293863 PubMed]
 
−
# '''TEX trial:''' Hatschek T, Carlsson L, Einbeigi Z, Lidbrink E, Linderholm B, Lindh B, Loman N, Malmberg M, Rotstein S, Söderberg M, Sundquist M, Walz TM, Hellström M, Svensson H, Aström G, Brandberg Y, Carstensen J, Fernö M, Bergh J. Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial. Breast Cancer Res Treat. 2012 Feb;131(3):939-47. Epub 2011 Nov 18. [https://doi.org/10.1007/s10549-011-1880-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22094937 PubMed] NCT01433614
 
−
# Lück HJ, Du Bois A, Loibl S, Schrader I, Huober J, Heilmann V, Beckmann M, Stähler A, Jackisch C, Hubalek M, Richter B, Stickeler E, Eidtmann H, Thomssen C, Untch M, Wollschläger K, Schuster T, von Minckwitz G; AGO Breast Cancer Study Group. Capecitabine plus paclitaxel versus epirubicin plus paclitaxel as first-line treatment for metastatic breast cancer: efficacy and safety results of a randomized, phase III trial by the AGO Breast Cancer Study Group. Breast Cancer Res Treat. 2013 Jun;139(3):779-87. Epub 2013 Jun 15. [https://doi.org/10.1007/s10549-013-2589-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23771714 PubMed]
 
−
 
 
−
==Epirubicin monotherapy {{#subobject:e941f2|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, 35 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:e75cc8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdi181 Feher et al. 2005]
 
−
|1996-1999
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Gemcitabine_monotherapy|Gemcitabine]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 35 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #2, 40 mg/m<sup>2</sup> {{#subobject:740b22|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="3" |[https://doi.org/10.1200/jco.1996.14.4.1146 Bastholt et al. 1996]
 
−
|rowspan=3|1987-1991
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#Epirubicin_monotherapy_2|Epirubicin]]; 60 mg/m<sup>2</sup>
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|2. [[#Epirubicin_monotherapy_2|Epirubicin]]; 90 mg/m<sup>2</sup>
 
−
| style="background-color:#d73027" |Inferior TTP
 
−
|-
 
−
|3. [[#Epirubicin_monotherapy_2|Epirubicin]]; 135 mg/m<sup>2</sup>
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #3, 50 mg/m<sup>2</sup> {{#subobject:7408cc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/0277-5379(90)90255-r Gundersen et al. 1990]
 
−
|1984-1986
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Doxorubicin_monotherapy_2|Doxorubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of ORR/OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''14-day cycles'''
 
−
 
 
−
===Regimen variant #4, 60 mg/m<sup>2</sup> {{#subobject:5b43d9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a057748 Nielsen et al. 1990]
 
−
|1983-1986
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_.26_Vindesine_99|Epirubicin & Vindesine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
| [https://doi.org/10.1200/jco.1996.14.4.1146 Bastholt et al. 1996]
 
−
|1987-1991
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#Epirubicin_monotherapy_2|Epirubicin]]; 40 mg/m<sup>2</sup><br> 2. [[#Epirubicin_monotherapy_2|Epirubicin]]; 90 mg/m<sup>2</sup><br> 3. [[#Epirubicin_monotherapy_2|Epirubicin]]; 135 mg/m<sup>2</sup>
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #5, 70 mg/m<sup>2</sup>, 2 out of 4 weeks {{#subobject:03c8f3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1007/s002800000178 Nielsen et al. 2000]
 
−
|1987-1990
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_Epirubicin_88|Cisplatin & Epirubicin]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior TTP
 
−
| style="background-color:#1a9850" |Superior toxicity
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 70 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycles until maximum dose of epirubicin reached (1000 mg/m<sup>2</sup>)'''
 
−
 
 
−
===Regimen variant #6, 75 mg/m<sup>2</sup> {{#subobject:e8gaa6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1991.9.2.305 Bonneterre & Hurteloup 1991]
 
−
|rowspan=2|NR
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#FEC_3|FEC]]; FEC 50
 
−
| style="background-color:#fc8d59" |Seems to have inferior ORR
 
−
|-
 
−
|[[#FEC_3|FEC]]; FEC 75
 
−
| style="background-color:#d73027" |Inferior ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #7, 90 mg/m<sup>2</sup> {{#subobject:e56ea6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1991.9.12.2148 Perez et al. 1991]
 
−
|1985-1988
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Doxorubicin_monotherapy_2|Doxorubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of ORR/OS
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.1996.14.4.1146 Bastholt et al. 1996]
 
−
|rowspan=2|1987-1991
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Epirubicin_monotherapy_2|Epirubicin]]; 40 mg/m<sup>2</sup>
 
−
| style="background-color:#1a9850" |Superior TTP
 
−
|-
 
−
|2. [[#Epirubicin_monotherapy_2|Epirubicin]]; 60 mg/m<sup>2</sup><br> 3. [[#Epirubicin_monotherapy_2|Epirubicin]]; 135 mg/m<sup>2</sup>
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.11.503 Ejlertsen et al. 2004 (SBG 9403)]
 
−
|1995-1999
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_.26_Vinorelbine_.28VE.29|VE]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #8, 120 mg/m<sup>2</sup>, split doses {{#subobject:45c4d9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.4.1165 Dogliotti et al. 1996]
 
−
|1991-1993
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_.26_Lonidamine_77|Epirubicin & Lonidamine]]
 
−
| style="background-color:#d73027" |Inferior ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2002.08.012 Berruti et al. 2002]
 
−
|1995-1999
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Cisplatin_.26_Epirubicin_99|Cisplatin & Epirubicin]]<br>2. [[#Cisplatin.2C_Epirubicin.2C_Lonidamine_77|Cisplatin, Epirubicin, Lonidamine]]<br>3. [[#Epirubicin_.26_Lonidamine_77|Epirubicin & Lonidamine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #9, 135 mg/m<sup>2</sup> {{#subobject:e0a80d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| [https://doi.org/10.1200/jco.1996.14.4.1146 Bastholt et al. 1996]
 
−
|1987-1991
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Epirubicin_monotherapy_2|Epirubicin]]; 40 mg/m<sup>2</sup><br> 2. [[#Epirubicin_monotherapy_2|Epirubicin]]; 60 mg/m<sup>2</sup><br> 3. [[#Epirubicin_monotherapy_2|Epirubicin]]; 90 mg/m<sup>2</sup>
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 135 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# Gundersen S, Kvinnsland S, Klepp O, Lund E, Høst H; Norwegian Breast Cancer Group. Weekly Adriamycin vs 4-epidoxorubicin every second week in advanced breast cancer: a randomized trial. Eur J Cancer. 1990 Jan;26(1):45-8. [https://doi.org/10.1016/0277-5379(90)90255-r link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2138477 PubMed]
 
−
# Nielsen D, Dombernowsky P, Skovsgaard T, Jensen J, Andersen E, Engelholm SA, Hansen M. Epirubicin or epirubicin and vindesine in advanced breast cancer: a phase III study. Ann Oncol. 1990 Jul;1(4):275-80. [https://doi.org/10.1093/oxfordjournals.annonc.a057748 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2265137 PubMed]
 
−
# Bonneterre J, Hurteloup P; French Epirubicin Study Group. A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. J Clin Oncol. 1991 Feb;9(2):305-12. [https://doi.org/10.1200/JCO.1991.9.2.305 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1988577 PubMed]
 
−
# Perez DJ, Harvey VJ, Robinson BA, Atkinson CH, Dady PJ, Kirk AR, Evans BD, Chapman PJ. A randomized comparison of single-agent doxorubicin and epirubicin as first-line cytotoxic therapy in advanced breast cancer. J Clin Oncol. 1991 Dec;9(12):2148-52. [https://doi.org/10.1200/JCO.1991.9.12.2148 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1960557 PubMed]
 
−
# Bastholt L, Dalmark M, Gjedde SB, Pfeiffer P, Pedersen D, Sandberg E, Kjaer M, Mouridsen HT, Rose C, Nielsen OS, Jakobsen P, Bentzen SM; Danish Breast Cancer Cooperative Group. Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: a randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 1996 Apr;14(4):1146-55. [https://doi.org/10.1200/jco.1996.14.4.1146 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8648369 PubMed]
 
−
# Dogliotti L, Berruti A, Buniva T, Zola P, Baù MG, Farris A, Sarobba MG, Bottini A, Alquati P, Deltetto F, Gosso P, Monzeglio C, Moro G, Sussio M, Perroni D. Lonidamine significantly increases the activity of epirubicin in patients with advanced breast cancer: results from a multicenter prospective randomized trial. J Clin Oncol. 1996 Apr;14(4):1165-72. [https://doi.org/10.1200/JCO.1996.14.4.1165 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8648371 PubMed]
 
−
# Nielsen D, Dombernowsky P, Larsen SK, Hansen OP, Skovsgaard T. Epirubicin or epirubicin and cisplatin as first-line therapy in advanced breast cancer: a phase III study. Cancer Chemother Pharmacol. 2000;46(6):459-66. [https://doi.org/10.1007/s002800000178 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11138459 PubMed]
 
−
# Berruti A, Bitossi R, Gorzegno G, Bottini A, Alquati P, De Matteis A, Nuzzo F, Giardina G, Danese S, De Lena M, Lorusso V, Farris A, Sarobba MG, DeFabiani E, Bonazzi G, Castiglione F, Bumma C, Moro G, Bruzzi P, Dogliotti L; Epirubicin-Lonidamine Group. Time to progression in metastatic breast cancer patients treated with epirubicin is not improved by the addition of either cisplatin or lonidamine: final results of a phase III study with a factorial design. J Clin Oncol. 2002 Oct 15;20(20):4150-9. [https://doi.org/10.1200/JCO.2002.08.012 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12377958 PubMed]
 
−
# '''SBG 9403:''' Ejlertsen B, Mouridsen HT, Langkjer ST, Andersen J, Sjöström J, Kjaer M; Scandinavian Breast Group. Phase III study of intravenous vinorelbine in combination with epirubicin versus epirubicin alone in patients with advanced breast cancer: a Scandinavian Breast Group Trial (SBG9403). J Clin Oncol. 2004 Jun 15;22(12):2313-20. [https://doi.org/10.1200/JCO.2004.11.503 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15197192 PubMed]
 
−
# Feher O, Vodvarka P, Jassem J, Morack G, Advani SH, Khoo KS, Doval DC, Ermisch S, Roychowdhury D, Miller MA, von Minckwitz G. First-line gemcitabine versus epirubicin in postmenopausal women aged 60 or older with metastatic breast cancer: a multicenter, randomized, phase III study. Ann Oncol. 2005 Jun;16(6):899-908. Epub 2005 Apr 8. [https://doi.org/10.1093/annonc/mdi181 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15821120 PubMed]
 
−
 
 
−
==FAC {{#subobject:b0cb|Regimen=1}}==
 
−
 
 
−
FAC: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
 
−
<br>CAF: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil
 
−
<br>AFC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil, '''<u>C</u>'''yclophosphamide
 
−
===Regimen variant #1, 500/50/500 {{#subobject:c92289|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197708)40:2%3C625::AID-CNCR2820400206%3E3.0.CO;2-M Smalley et al. 1977]
 
−
|1974-1975
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[Breast_cancer_-_historical#CMFVP_2|CMFVP]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1988.6.10.1611 Bennett et al. 1988]
 
−
|1983-1985
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CNF_99|CNF]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of TTF/OS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199111073251904 Muss et al. 1991]
 
−
|1984-1989
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/full/10.1002/%28SICI)1097-0142%2819990301%2985%3A5%3C1091%3A%3AAID-CNCR12%3E3.0.CO%3B2-A Blajman et al. 1999]
 
−
|1991-1994
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Vinorelbine_.28NA.29_99|NA]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.6.1707 Jassem et al. 2001]
 
−
|1996-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Paclitaxel_.28AT.29_2|AT (Taxol)]]
 
−
| style="background-color:#d73027" |Inferior OS<sup>2</sup>
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.06.236 Bontenbal et al. 2005]
 
−
|1997-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Doxorubicin_.28AT.29|AT (Taxotere)]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FAC_.26_Bevacizumab|FAC & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for Smalley et al. 1977 is based on the 1983 update.''<br>
 
−
''<sup>2</sup>Reported efficacy for Jassem et al. 2001 is based on the 2009 update.''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 6 to 8 cycles'''
 
−
====Subsequent treatment====
 
−
*Muss et al. 1991: [[Breast_cancer_-_historical#CMFP|CMFP]] versus [[Breast_cancer_-_null_regimens#Observation_2|observation]], then CMFP at progression
 
−
 
 
−
===Regimen variant #2, 600/50/600 {{#subobject:dbd450|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/BF00666487 Alonso et al. 1995]
 
−
|1988-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CNF_99|CNF]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of ORR/OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup>/day IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 10 cycles'''
 
−
 
 
−
===Regimen variant #3, 800/40/400 {{#subobject:dajb20|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197806)41:6%3C2078::AID-CNCR2820410602%3E3.0.CO;2-Q Tranum et al. 1978]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|1. [[#Doxorubicin_.26_Fluorouracil_.28FA.29_99|AF]]<br> 2. [[Breast_cancer_-_historical#CAMF|AFCM]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #4, 1000/40/500 {{#subobject:d56b20|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1995.13.6.1443 Aisner et al. 1995 (CALGB 8281)]
 
−
|1982-1987
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#VATH_99|VATH]]<br> 2. [[#VATH.2FCMFVP_99|VATH/CMFVP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2003.05.119 Parnes et al. 2003 (CALGB 9140)]
 
−
|1991-1995
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FAC_.26_Folinic_acid_99|FAC & Leucovorin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: Aisner et al. 1995 does not describe dosing; included here because it is a CALGB study.''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #5, 1000/50/500 {{#subobject:ed75b0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197911)44:5%3C1955::AID-CNCR2820440559%3E3.0.CO;2-P Hortobagyi et al. 1979]
 
−
|1974-NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FAC-BCG_99|FAC-BCG]]
 
−
| style="background-color:#d73027" |Inferior OS in responders
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8 or days 1 & 4
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #6, 1000/50/1400 {{#subobject:b25f0f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1987.5.10.1523 Aisner et al. 1987]
 
−
|rowspan=2|1976-1980
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[Breast_cancer_-_historical#CAFVP|CAFVP]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[#CMF_2|CMF]]
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|[https://doi.org/10.1007/BF01807589 Kardinal et al. 1983 (CALGB 8081)]
 
−
|1980-1982
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#CAFT_99|CAFT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
 
 
−
'''28-day cycle for up to 9 cycles'''
 
−
 
 
−
===Regimen variant #7, 1000/60/1400 x 6 {{#subobject:b89f0f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.2.262 Sledge et al. 2000 (ECOG E3186)]
 
−
|1988-1992
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CAFTH_88|CAFTH]]
 
−
| style="background-color:#fee08b" |Might have inferior TTF
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
 
 
−
'''28-day cycle for up to 6 cycles'''
 
−
 
 
−
===Regimen variant #8, 1000/60/1400, maximum doxorubicin of 500 mg/m<sup>2</sup> {{#subobject:b93f0f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1985.3.7.932 Cummings et al. 1985]
 
−
|1978-1979
 
−
| style="background-color:#1a9851" |Randomized (E-de-esc)
 
−
|[[Breast_cancer_-_historical#CMFP_2|CMFP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1987.5.6.881 Falkson et al. 1987 (ECOG E2177)]
 
−
|NR-1983
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#O.2BCAF_99|O+CAF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/TTF/OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
 
 
−
'''28-day cycles until maximum cumulative dose of doxorubicin of 500 mg/m<sup>2</sup>'''
 
−
 
 
−
===Regimen variant #9, 1000/60/1400, indefinite {{#subobject:b89f0f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J Bull et al. 1978]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CMF_2|CMF]]
 
−
| style="background-color:#d9ef8b" |Might have superior ORR
 
−
|-
 
−
|[https://www.ejcancer.com/article/0959-8049(94)90123-6/pdf Tominaga et al. 1994]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer_-_historical#CAF_.26_MPA|CAF & MPA]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior ORR
 
−
|-
 
−
|}
 
−
''Note: the dosing details of Tominaga et al. 1994 are not described in the abstract.''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# Smalley RV, Carpenter J, Bartolucci A, Vogel C, Krauss S; Southeastern Cancer Study Group. A comparison of cyclophosphamide, adriamycin, 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone (CMFVP) in patients with metastatic breast cancer: a Southeastern Cancer Study Group project. Cancer. 1977 Aug;40(2):625-32. [https://doi.org/10.1002/1097-0142(197708)40:2%3C625::AID-CNCR2820400206%3E3.0.CO;2-M link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/329975 PubMed]
 
−
## '''Update:''' Smalley RV, Lefante J, Bartolucci A, Carpenter J, Vogel C, Krauss S. A comparison of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) in patients with advanced breast cancer. Breast Cancer Res Treat. 1983;3(2):209-20. [https://doi.org/10.1007/BF01803563 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6688538 PubMed]
 
−
# Bull JM, Tormey DC, Li SH, Carbone PP, Falkson G, Blom J, Perlin E, Simon R. A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer. 1978 May;41(5):1649-57. [https://doi.org/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J link to original article] [https://pubmed.ncbi.nlm.nih.gov/348293 PubMed]
 
−
# Tranum B, Hoogstraten B, Kennedy A, Vaughn CB, Samal B, Thigpen T, Rivkin S, Smith F, Palmer RL, Costanzi J, Tucker WG, Wilson H, Maloney TR; [[Study_Groups#SWOG|SWOG]]. Adriamycin in combination for the treatment of breast cancer: a Southwest Oncology Group study. Cancer. 1978 Jun;41(6):2078-83. [https://doi.org/10.1002/1097-0142(197806)41:6%3C2078::AID-CNCR2820410602%3E3.0.CO;2-Q link to original article] [https://pubmed.ncbi.nlm.nih.gov/657081 PubMed]
 
−
# Hortobagyi GN, Gutterman JU, Blumenschein GR, Tashima CK, Burgess MA, Einhorn L, Buzdar AU, Richman SP, Hersh EM. Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG. Cancer. 1979 Nov;44(5):1955-62. [https://doi.org/10.1002/1097-0142(197911)44:5%3C1955::AID-CNCR2820440559%3E3.0.CO;2-P link to original article] [https://pubmed.ncbi.nlm.nih.gov/387212 PubMed]
 
−
# Cummings FJ, Gelman R, Horton J. Comparison of CAF versus CMFP in metastatic breast cancer: analysis of prognostic factors. J Clin Oncol. 1985 Jul;3(7):932-40. [https://doi.org/10.1200/JCO.1985.3.7.932 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3894587 PubMed]
 
−
# '''ECOG E2177:''' Falkson G, Gelman RS, Tormey DC, Falkson CI, Wolter JM, Cummings FJ. Treatment of metastatic breast cancer in premenopausal women using CAF with or without oophorectomy: an Eastern Cooperative Oncology Group Study. J Clin Oncol. 1987 Jun;5(6):881-9. [https://doi.org/10.1200/JCO.1987.5.6.881 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3585444 PubMed]
 
−
## '''Update:''' Falkson G, Holcroft C, Gelman RS, Tormey DC, Wolter JM, Cummings FJ. Ten-year follow-up study of premenopausal women with metastatic breast cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 1995 Jun;13(6):1453-8. [https://doi.org/10.1200/JCO.1995.13.6.1453 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7751892 PubMed]
 
−
# Aisner J, Weinberg V, Perloff M, Weiss R, Perry M, Korzun A, Ginsberg S, Holland JF; [[Study_Groups#CALGB|CALGB]]. Chemotherapy versus chemoimmunotherapy (CAF v CAFVP v CMF each +/- MER) for metastatic carcinoma of the breast: a CALGB study. J Clin Oncol. 1987 Oct;5(10):1523-33. [https://doi.org/10.1200/JCO.1987.5.10.1523 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3655855 PubMed]
 
−
# '''CALGB 8081:''' Kardinal CG, Perry MC, Weinberg V, Wood W, Ginsberg S, Raju RN. Chemoendocrine therapy vs chemotherapy alone for advanced breast cancer in postmenopausal women: preliminary report of a randomized study. Breast Cancer Res Treat. 1983;3(4):365-71. [https://doi.org/10.1007/BF01807589 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6365209 PubMed]
 
−
## '''Update:''' Perry MC, Kardinal CG, Korzun AH, Ginsberg SJ, Raich PC, Holland JF, Ellison RR, Kopel S, Schilling A, Aisner J, Schulman P, Weinberg V, Rice MA, Wood W. Chemohormonal therapy in advanced carcinoma of the breast: Cancer and Leukemia Group B protocol 8081. J Clin Oncol. 1987 Oct;5(10):1534-45. [https://doi.org/10.1200/JCO.1987.5.10.1534 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3655856 PubMed]
 
−
# Bennett JM, Muss HB, Doroshow JH, Wolff S, Krementz ET, Cartwright K, Dukart G, Reisman A, Schoch I. A randomized multicenter trial comparing mitoxantrone, cyclophosphamide, and fluorouracil with doxorubicin, cyclophosphamide, and fluorouracil in the therapy of metastatic breast carcinoma. J Clin Oncol. 1988 Oct;6(10):1611-20. [https://doi.org/10.1200/JCO.1988.6.10.1611 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3049953 PubMed]
 
−
# Muss HB, Case LD, Richards F 2nd, White DR, Cooper MR, Cruz JM, Powell BL, Spurr CL, Capizzi RL; Piedmont Oncology Association. Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. N Engl J Med. 1991 Nov 7;325(19):1342-8. [https://doi.org/10.1056/NEJM199111073251904 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1922236 PubMed]
 
−
# Tominaga T, Abe O, Ohshima A, Hayasaka H, Uchino J, Abe R, Enomoto K, Izuo M, Watanabe H, Takatani O, Yoshida M, Sakai K, Koyama H, Hattori T, Senoo T, Monden Y, Nomura Y. Comparison of chemotherapy with or without medroxyprogesterone acetate for advanced or recurrent breast cancer. Eur J Cancer. 1994;30A(7):959-64. [https://www.ejcancer.com/article/0959-8049(94)90123-6/pdf link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7946592 PubMed]
 
−
# Alonso MC, Tabernero JM, Ojeda B, Llanos M, Solà C, Climent MA, Seguí MA, López JJ. A phase III randomized trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) versus cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) in patients with metastatic breast cancer. Breast Cancer Res Treat. 1995 Apr;34(1):15-24. [https://doi.org/10.1007/BF00666487 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7749156 PubMed]
 
−
# '''CALGB 8281:''' Aisner J, Cirrincione C, Perloff M, Perry M, Budman D, Abrams J, Panasci L, Muss H, Citron M, Holland J, Wood W, Henderson IC. Combination chemotherapy for metastatic or recurrent carcinoma of the breast--a randomized phase III trial comparing CAF versus VATH versus VATH alternating with CMFVP: Cancer and Leukemia Group B Study 8281. J Clin Oncol. 1995 Jun;13(6):1443-52. [https://doi.org/10.1200/JCO.1995.13.6.1443 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/7751891 PubMed]
 
−
# Blajman C, Balbiani L, Block J, Coppola F, Chacon R, Fein L, Bonicatto S, Alvarez A, Schmilovich A, Delgado FM. A prospective, randomized Phase III trial comparing combination chemotherapy with cyclophosphamide, doxorubicin, and 5-fluorouracil with vinorelbine plus doxorubicin in the treatment of advanced breast carcinoma. Cancer. 1999 Mar 1;85(5):1091-7. [https://doi.org/full/10.1002/%28SICI)1097-0142%2819990301%2985%3A5%3C1091%3A%3AAID-CNCR12%3E3.0.CO%3B2-A link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10091793 PubMed]
 
−
# '''ECOG E3186:''' Sledge GW Jr, Hu P, Falkson G, Tormey D, Abeloff M. Comparison of chemotherapy with chemohormonal therapy as first-line therapy for metastatic, hormone-sensitive breast cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2000 Jan;18(2):262-6. [https://doi.org/10.1200/JCO.2000.18.2.262 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10637238 PubMed]
 
−
# Jassem J, Pieńkowski T, Płuzańska A, Jelic S, Gorbunova V, Mrsic-Krmpotic Z, Berzins J, Nagykalnai T, Wigler N, Renard J, Munier S, Weil C; Central & Eastern Europe and Israel Pacitaxel Breast Cancer Study Group. Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial. J Clin Oncol. 2001 Mar 15;19(6):1707-15. [https://doi.org/10.1200/JCO.2001.19.6.1707 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11251000 PubMed]
 
−
##'''Update:''' Jassem J, Pienkowski T, Pluzanska A, Jelic S, Gorbunova V, Berzins J, Nagykalnai T, Biganzoli L, Aloe A, Astier L, Munier S. Doxorubicin and paclitaxel versus fluorouracil, doxorubicin and cyclophosphamide as first-line therapy for women with advanced breast cancer: long-term analysis of the previously published trial. Onkologie. 2009 Sep;32(8-9):468-72. Epub 2009 Jul 20. [https://doi.org/10.1159/000226210 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19745590/ PubMed]
 
−
# '''CALGB 9140:''' Parnes HL, Cirrincione C, Aisner J, Berry DA, Allen SL, Abrams J, Chuang E, Cooper MR, Perry MC, Duggan DB, Szatrowski TP, Henderson IC, Norton L; [[Study_Groups#CALGB|CALGB]]. Phase III study of cyclophosphamide, doxorubicin, and fluorouracil (CAF) plus leucovorin versus CAF for metastatic breast cancer: Cancer and Leukemia Group B 9140. J Clin Oncol. 2003 May 1;21(9):1819-24. [https://doi.org/10.1200/JCO.2003.05.119 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12721259 PubMed]
 
−
# Bontenbal M, Creemers GJ, Braun HJ, de Boer AC, Janssen JT, Leys RB, Ruit JB, Goey SH, van der Velden PC, Kerkhofs LG, Schothorst KL, Schmitz PI, Bokma HJ, Verweij J, Seynaeve C; Dutch Community Setting Trial for the Clinical Trial Group. Phase II to III study comparing doxorubicin and docetaxel with fluorouracil, doxorubicin, and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: results of a Dutch Community Setting Trial for the Clinical Trial Group of the Comprehensive Cancer Centre. J Clin Oncol. 2005 Oct 1;23(28):7081-8. [https://doi.org/10.1200/JCO.2005.06.236 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16192591 PubMed]
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
 
 
−
==FAC & Bevacizumab {{#subobject:4e04d9|Regimen=1}}==
 
−
 
 
−
FAC & Bevacizumab: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, Bevacizumab
 
−
===Regimen {{#subobject:961016|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#FAC_3|FAC]]
 
−
| style="background-color:#1a9850" |Superior PFS <br>(HR 0.64, 95% CI 0.52-0.80)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Bevacizumab_monotherapy_2|Bevacizumab]] maintenance, if no PD
 
−
===References===
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
 
 
−
==FEC {{#subobject:ed96e7|Regimen=1}}==
 
−
 
 
−
FEC: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide
 
−
<br>CEF: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>F</u>'''luorouracil
 
−
===Regimen variant #1, 500/50/500 ("FEC 50") {{#subobject:d92480|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1991.9.2.305 Bonneterre & Hurteloup 1991]
 
−
|rowspan=2|NR
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_monotherapy_2|Epirubicin]]
 
−
| style="background-color:#91cf60" |Seems to have superior ORR
 
−
|-
 
−
|[[#FEC_3|FEC]]; FEC 75
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1993.11.7.1253 Focan et al. 1993]
 
−
|1985-1990
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_3|FEC]]; FEC 100
 
−
| style="background-color:#fc8d59" |Seems to have inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1023/a:1008295427877 Brufman et al. 1997 (HEPI 010)]
 
−
|1989-1992
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_3|FEC]]; FEC 100
 
−
| style="background-color:#d73027" |Inferior ORR
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdf306 Heidemann et al. 2002 (GER-AIO-01/92)]
 
−
|1992-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Mitoxantrone_monotherapy_99|Mitoxantrone]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 to 12 cycles'''
 
−
 
 
−
===Regimen variant #2, 500/60/500 {{#subobject:eb63d8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1993.11.3.467 Blomqvist et al. 1993]
 
−
|1987-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_3|FEC]]; weekly
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #3, 500/75/500 ("FEC 75") {{#subobject:0df196|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1991.9.2.305 Bonneterre & Hurteloup 1991]
 
−
|rowspan=2|NR
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Epirubicin_monotherapy_2|Epirubicin]]
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|[[#FEC_3|FEC]]; FEC 50
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(00)00068-X Pacini et al. 2000]
 
−
|1991-1996
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Epirubicin_.26_Mitomycin_.28EM.29_88|EM]]<br>2. [[#Epirubicin_.26_Mitomycin_.28EM.29_.26_Lonidamine_77|EM & Lonidamine]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1179/joc.2003.15.2.184 Capotorto et al. 2003]
 
−
|rowspan=2|1995-1998
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Dose-dense_FEC_88|ddFEC]]
 
−
| style="background-color:#d73027" |Inferior ORR
 
−
|-
 
−
|2. [[#Dose-dense_MMM_99|ddMMM]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of ORR
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409942/ Bonneterre et al. 2004]
 
−
|1998-2000
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#Docetaxel_.26_Epirubicin_.28DE.29_2|DE]]
 
−
| style="background-color:#d73027" |Inferior ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #4, 500/90/500 {{#subobject:8aa343|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.12.106 Zielinksi et al. 2005 (CECOG BM1)]
 
−
|1999-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#GET_99|GET]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_.26_Bevacizumab|FEC & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: this is the lower bound of the dosing range allowed in RIBBON-1.''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 8 cycles'''
 
−
 
 
−
===Regimen variant #5, 500/100/500 ("FEC 100") {{#subobject:33c356|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1993.11.7.1253 Focan et al. 1993]
 
−
|1985-1990
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#FEC_3|FEC]]; FEC 50
 
−
| style="background-color:#91cf60" |Seems to have superior TTP
 
−
|-
 
−
|[https://doi.org/10.1023/a:1008295427877 Brufman et al. 1997 (HEPI 010)]
 
−
|1989-1992
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#FEC_3|FEC]]; FEC 50
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_.26_Bevacizumab|FEC & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: this is the upper bound of the dosing range allowed in RIBBON-1.''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
**Note: in Focan et al. 1993, dose was split: 50 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
 
 
−
===Regimen variant #6, 600/60/600 ("CEF21") {{#subobject:80e015|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1987.5.3.339 Conte et al. 1987]
 
−
|1983-1985
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#DES-CEF_99|DES-CEF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a010637 Conte et al. 1996]
 
−
|1985-1990
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#DES-CEF_99|DES-CEF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(05)80145-5/pdf Ejlertsen et al. 1993]
 
−
|1986-1989
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC_3|FEC]] x 18 mo
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.8.2213 Del Mastro et al. 2001]
 
−
|1994-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#HD-CEF14_99|HD-CEF14]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: dosing information was not available in the abstract of Ejlertsen et al. 1993; this dosing has been used in other studies by this group.''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for 8 to 12 cycles'''
 
−
 
 
−
===Regimen variant #7, 1000/50/500 until max anthracycline {{#subobject:caf441|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1988.6.6.976 Ambrosini et al. 1988]
 
−
|1983-1985
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#FAC_3|FAC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint
 
−
| style="background-color:#1a9850" |Less toxic
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 14 cycles (maximum of 700 mg/m<sup>2</sup> epirubicin)'''
 
−
 
 
−
===Regimen variant #8, 1000/60/1400 {{#subobject:8505fe|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1023/a:1006387801960 Esteban et al. 1999]
 
−
|1987-1993
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CNF_99|CNF]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Epirubicin (Ellence)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #9, 1000/100/800 {{#subobject:830d7f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2001.19.4.943 Ackland et al. 2001 (HEPI 013)]
 
−
|1990-1992
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CMF_2|CMF]]
 
−
| style="background-color:#1a9850" |Superior TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
 
−
'''28-day cycle for 6 to 8 cycles'''
 
−
 
 
−
===References===
 
−
# Conte PF, Pronzato P, Rubagotti A, Alama A, Amadori D, Demicheli R, Gardin G, Gentilini P, Jacomuzzi A, Lionetto R, Monzeglio C, Nicolin A, Rosso R, Sismondi P, Sussio M, Santi L. Conventional versus cytokinetic polychemotherapy with estrogenic recruitment in metastatic breast cancer: results of a randomized cooperative trial. J Clin Oncol. 1987 Mar;5(3):339-47. [https://doi.org/10.1200/JCO.1987.5.3.339 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3546611 PubMed]
 
−
# Ambrosini G, Balli M, Garusi G, Demicheli R, Jirillo A, Bonciarelli G, Bruscagnin G, Fila G, Bumma C, Lacroix F, Buzzi F, Di Costanzo F, Padalino D, Brugia M, Calabresi F, Natali M, Cartei G, Chiesa G, Blasina B, Ciambellotti E, Moro G, D'Aquino S, Altavilla G, Adamo V, De Maria D, Falchi AM, Bertoncelli P, Farris A, Fiorentino M, Fornasiero A, Fosser V, Daniele O, Foggi CM, Speranza GB, Sartori S, Camilluzzi E, Gallo L, Poggio R, Secondo V, Gambi A, Grignani F, Capodicasa E, Lopez M, Papaldo P, Di Lauro L, Vici P, Marenco G, Folco U, Bonanni F, Marsilio P, Palazzotto G, Di Carlo A, Cusimano MP, Pastorino G, Puccetti C, Giusto M, Rausa L, Gebbia N, Palmeri S, D'Alessandro N, Saccani F, Becchi G, Schieppati G, Spinelli I, Tagliagambe A, Tonato M, Minotti V, Ardia A, Viaro D, De Micheli P, Zingali G, Sacchetti G, Intini C; Italian Multicentre Breast Study with Epirubicin. Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial. J Clin Oncol. 1988 Jun;6(6):976-82. [https://doi.org/10.1200/JCO.1988.6.6.976 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2897433 PubMed]
 
−
# Bonneterre J, Hurteloup P; French Epirubicin Study Group. A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. J Clin Oncol. 1991 Feb;9(2):305-12. [https://doi.org/10.1200/JCO.1991.9.2.305 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1988577 PubMed]
 
−
# Ejlertsen B, Pfeiffer P, Pedersen D, Mouridsen HT, Rose C, Overgaard M, Sandberg E, Kristensen B. Decreased efficacy of cyclophosphamide, epirubicin and 5-fluorouracil in metastatic breast cancer when reducing treatment duration from 18 to 6 months. Eur J Cancer. 1993;29A(4):527-31. [https://www.ejcancer.com/article/S0959-8049(05)80145-5/pdf link to original article] [https://pubmed.ncbi.nlm.nih.gov/8435205 PubMed]
 
−
# Blomqvist C, Elomaa I, Rissanen P, Hietanen P, Nevasaari K, Helle L. Influence of treatment schedule on toxicity and efficacy of cyclophosphamide, epirubicin, and fluorouracil in metastatic breast cancer: a randomized trial comparing weekly and every-4-week administration. J Clin Oncol. 1993 Mar;11(3):467-73. [https://doi.org/10.1200/JCO.1993.11.3.467 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8445422 PubMed]
 
−
# Focan C, Andrien JM, Closon MT, Dicato M, Driesschaert P, Focan-Henrard D, Lemaire M, Lobelle JP, Longree L, Ries F. Dose-response relationship of epirubicin-based first-line chemotherapy for advanced breast cancer: a prospective randomized trial. J Clin Oncol. 1993 Jul;11(7):1253-63. [https://doi.org/10.1200/JCO.1993.11.7.1253 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8315422 PubMed]
 
−
# Conte PF, Baldini E, Gardin G, Pronzato P, Amadori D, Carnino F, Monzeglio C, Gentilini P, Gallotti P, DeMicheli R, Venturini M, Rubagotti A, Rosso R; GONO. Chemotherapy with or without estrogenic recruitment in metastatic breast cancer: a randomized trial of the Gruppo Oncologico Nord Ovest (GONO). Ann Oncol. 1996 Jul;7(5):487-90. [https://doi.org/10.1093/oxfordjournals.annonc.a010637 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8839903 PubMed]
 
−
# '''HEPI 010:''' Brufman G, Colajori E, Ghilezan N, Lassus M, Martoni A, Perevodchikova N, Tosello C, Viaro D, Zielinski C; Epirubicin High Dose (HEPI 010) Study Group. Doubling epirubicin dose intensity (100 mg/m<sup>2</sup> versus 50 mg/m<sup>2</sup>) in the FEC regimen significantly increases response rates: an international randomised phase III study in metastatic breast cancer. Ann Oncol. 1997 Feb;8(2):155-62. [https://doi.org/10.1023/a:1008295427877 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9093724 PubMed]
 
−
# Esteban E, Lacave AJ, Fernández JL, Corral N, Buesa JM, Estrada E, Palacio I, Vieitez JM, Muñiz I, Alvarez E. Phase III trial of cyclophosphamide, epirubicin, fluorouracil (CEF) versus cyclophosphamide, mitoxantrone, fluorouracil (CNF) in women with metastatic breast cancer. Breast Cancer Res Treat. 1999 Nov;58(2):141-50. [https://doi.org/10.1023/a:1006387801960 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10674879 PubMed]
 
−
# Pacini P, Rinaldini M, Algeri R, Guarneri A, Tucci E, Barsanti G, Neri B, Bastiani P, Marzano S, Fallai C. FEC (5-fluorouracil, epidoxorubicin and cyclophosphamide) versus EM (epidoxorubicin and mitomycin-C) with or without lonidamine as first-line treatment for advanced breast cancer, a multicentric randomised study: final results. Eur J Cancer. 2000 May;36(8):966-75. [https://www.ejcancer.com/article/S0959-8049(00)00068-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10885599 PubMed]
 
−
# '''HEPI 013:''' Ackland SP, Anton A, Breitbach GP, Colajori E, Tursi JM, Delfino C, Efremidis A, Ezzat A, Fittipaldo A, Kolaric K, Lopez M, Viaro D; HEPI 013 study group. Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study. J Clin Oncol. 2001 Feb 15;19(4):943-53. [https://doi.org/10.1200/jco.2001.19.4.943 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11181656 PubMed]
 
−
# Del Mastro L, Venturini M, Lionetto R, Carnino F, Guarneri D, Gallo L, Contu A, Pronzato P, Vesentini L, Bergaglio M, Comis S, Rosso R; GONO; MIG. Accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with standard CEF in metastatic breast cancer patients: results of a multicenter, randomized phase III study of the Italian Gruppo Oncologico Nord-Ouest-Mammella Inter Gruppo Group. J Clin Oncol. 2001 Apr 15;19(8):2213-21. [https://doi.org/10.1200/JCO.2001.19.8.2213 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11304774 PubMed]
 
−
# '''GER-AIO-01/92:''' Heidemann E, Stoeger H, Souchon R, Hirschmann WD, Bodenstein H, Oberhoff C, Fischer JT, Schulze M, Clemens M, Andreesen R, Mahlke M, König M, Scharl A, Fehnle K, Kaufmann M. Is first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial. Ann Oncol. 2002 Nov;13(11):1717-29. [https://doi.org/10.1093/annonc/mdf306 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12419743/ PubMed] NCT00002544
 
−
# Capotorto AM, Pavesi L, Pedrazzoli P, Da Prada GA, Zamagni C, Massidda B, Farris A, Martoni A, Lelli G, Robustelli della Cuna G. Randomized, controlled, multicenter phase III trial of standard-dose fluorouracil-epirubicin-cyclophosphamide (FEC), compared with time-intensive FEC (FEC-G) and mitoxantrone-methotrexate-mitomycin C (MMM-G) in metastatic breast carcinoma. J Chemother. 2003 Apr;15(2):184-91. [https://doi.org/10.1179/joc.2003.15.2.184 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12797397/ PubMed]
 
−
# Bonneterre J, Dieras V, Tubiana-Hulin M, Bougnoux P, Bonneterre ME, Delozier T, Mayer F, Culine S, Dohoulou N, Bendahmane B. Phase II multicentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer. Br J Cancer. 2004 Oct 18;91(8):1466-71. [https://www.nature.com/articles/6602179 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409942/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15381937 PubMed]
 
−
# '''CECOG BM1:''' Zielinski C, Beslija S, Mrsic-Krmpotic Z, Welnicka-Jaskiewicz M, Wiltschke C, Kahan Z, Grgic M, Tzekova V, Inbar M, Cervek J, Chernozemsky I, Szanto J, Spanik S, Wagnerova M, Ghilezan N, Pawlega J, Vrbanec D, Khamtsov D, Soldatenkova V, Brodowicz T. Gemcitabine, epirubicin, and paclitaxel versus fluorouracil, epirubicin, and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: a Central European Cooperative Oncology Group International, multicenter, prospective, randomized phase III trial. J Clin Oncol. 2005 Mar 1;23(7):1401-8. [https://doi.org/10.1200/JCO.2005.12.106 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15735116 PubMed]
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
 
 
−
==FEC & Bevacizumab {{#subobject:72fe69|Regimen=1}}==
 
−
 
 
−
FEC & Bevacizumab: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, Bevacizumab
 
−
===Regimen {{#subobject:cb9b3a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#FEC_3|FEC]]
 
−
| style="background-color:#1a9850" |Superior PFS <br>(HR 0.64, 95% CI 0.52-0.80)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 90 to 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 8 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Bevacizumab_monotherapy_2|Bevacizumab]] maintenance, if no PD
 
−
===References===
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
 
 
−
==Gemcitabine monotherapy {{#subobject:b240d6|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:7ea6c2|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1995.13.11.2731 Carmichael et al. 1995]
 
−
|NR
 
−
| style="background-color:#ffffbe" |Phase 2, less than 20 pts in this subgroup
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# Carmichael J, Possinger K, Phillip P, Beykirch M, Kerr H, Walling J, Harris AL. Advanced breast cancer: a phase II trial with gemcitabine. J Clin Oncol. 1995 Nov;13(11):2731-6. [https://doi.org/10.1200/jco.1995.13.11.2731 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7595731 PubMed]
 
−
 
 
−
==Gemcitabine & Paclitaxel {{#subobject:1285e|Regimen=1}}==
 
−
 
 
−
GT: '''<u>G</u>'''emcitabine & '''<u>T</u>'''axol (Paclitaxel)
 
−
<br>PG: '''<u>P</u>'''aclitaxel & '''<u>G</u>'''emcitabine
 
−
===Regimen variant #1, 6 cycles {{#subobject:5e5f66|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.45.2490 Park et al. 2013 (KCSG-BR07-02)]
 
−
|2007-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given second on day 1'''
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1, '''given first'''
 
−
 
 
−
'''21-day cycle for 6 cycles'''
 
−
====Subsequent treatment====
 
−
*[[#Gemcitabine_.26_Paclitaxel_2|PG]] maintenance versus [[Breast_cancer_-_null_regimens#Observation_2|Observation]]
 
−
 
 
−
===Regimen variant #2, indefinite {{#subobject:7a28ec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.11.9362 Albain et al. 2008]
 
−
|1999-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 18.6 vs 15.8 mo<br>(HR 0.78, 95% CI 0.64-0.96)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621657/ Del Mastro et al. 2013 (B9E-IT-S376)]
 
−
|2005-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Docetaxel_.26_Gemcitabine|GD]]; weekly<br> 2. [[#Docetaxel_.26_Gemcitabine|GD]]; q3wk<br> 3. [[#Gemcitabine_.26_Paclitaxel|GT]]; weekly
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 & 8, '''given second on day 1'''
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
<!-- Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003, and the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004. -->
 
−
# Albain KS, Nag SM, Calderillo-Ruiz G, Jordaan JP, Llombart AC, Pluzanska A, Rolski J, Melemed AS, Reyes-Vidal JM, Sekhon JS, Simms L, O'Shaughnessy J. Gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol. 2008 Aug 20;26(24):3950-7. [https://doi.org/10.1200/jco.2007.11.9362 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18711184 PubMed]
 
−
# '''B9E-IT-S376:''' Del Mastro L, Fabi A, Mansutti M, De Laurentiis M, Durando A, Merlo DF, Bruzzi P, La Torre I, Ceccarelli M, Kazeem G, Marchi P, Boy D, Venturini M, De Placido S, Cognetti F. Randomised phase 3 open-label trial of first-line treatment with gemcitabine in association with docetaxel or paclitaxel in women with metastatic breast cancer: a comparison of different schedules and treatments. BMC Cancer. 2013 Mar 28;13:164. [https://doi.org/10.1186/1471-2407-13-164 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621657/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23537313 PubMed] NCT00236899
 
−
# '''KCSG-BR07-02:''' Park YH, Jung KH, Im SA, Sohn JH, Ro J, Ahn JH, Kim SB, Nam BH, Oh DY, Han SW, Lee S, Park IH, Lee KS, Kim JH, Kang SY, Lee MH, Park HS, Ahn JS, Im YH. Phase III, multicenter, randomized trial of maintenance chemotherapy versus observation in patients with metastatic breast cancer after achieving disease control with six cycles of gemcitabine plus paclitaxel as first-line chemotherapy: KCSG-BR07-02. J Clin Oncol. 2013 May 10;31(14):1732-9. Epub 2013 Apr 8. [https://doi.org/10.1200/JCO.2012.45.2490 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23569309 PubMed] NCT00561119
 
−
 
 
−
==Cyclophosphamide & Non-pegylated liposomal doxorubicin (MC) {{#subobject:7ac8f8|Regimen=1}}==
 
−
 
 
−
MC: '''<u>M</u>'''yocet (non-pegylated liposomal doxorubicin) & '''<u>C</u>'''yclophosphamide
 
−
===Regimen variant #1, 60/600 {{#subobject:57bc79|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.spandidos-publications.com/ijo/45/5/2137 Lorusso et al. 2014]
 
−
|2006-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Non-pegylated_liposomal_doxorubicin_.26_Vinorelbine_77|NPLD & Vinorelbine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Non-pegylated liposomal doxorubicin (Myocet)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #2, 75/600 {{#subobject:57bc80|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdh393 Chan et al. 2004]
 
−
|1996-1997
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]]
 
−
| style="background-color:#1a9850" |Superior TTP<br>Median TTP: 7.7 vs 5.6 mo<br>(HR 0.66, 95% CI 0.45-0.94)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Non-pegylated liposomal doxorubicin (Myocet)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 8 cycles'''
 
−
 
 
−
===References===
 
−
# Chan S, Davidson N, Juozaityte E, Erdkamp F, Pluzanska A, Azarnia N, Lee LW. Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer. Ann Oncol. 2004 Oct;15(10):1527-34. [https://doi.org/10.1093/annonc/mdh393 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15367414 PubMed]
 
−
# Lorusso V, Giotta F, Bordonaro R, Maiello E, Del Prete S, Gebbia V, Filippelli G, Pisconti S, Cinieri S, Romito S, Riccardi F, Forcignanò R, Ciccarese M, Petrucelli L, Saracino V, Lupo LI, Gambino A, Leo S, Colucci G; Gruppo Oncologico Dell'Italia Meridionale. Non-pegylated liposome-encapsulated doxorubicin citrate plus cyclophosphamide or vinorelbine in metastatic breast cancer not previously treated with chemotherapy:a multicenter phase III study. Int J Oncol. 2014 Nov;45(5):2137-42. Epub 2014 Aug 18. [https://www.spandidos-publications.com/ijo/45/5/2137 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25176223 PubMed]
 
−
 
 
−
==Paclitaxel monotherapy, weekly {{#subobject:3e5448|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, 80 mg/m<sup>2</sup> weekly {{#subobject:718d5b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2001.19.22.4216 Perez et al. 2001]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.11.6699 Seidman et al. 2008 (CALGB 9840)]
 
−
|1998-NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]; q3wk
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 24 vs 12 mo<br>(HR 0.78, 95% CI 0.65-0.94)
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-008-0047-9 Fountzilas et al. 2008]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_88|Carboplatin & Paclitaxel]]<br> 2. [[#Docetaxel_.26_Gemcitabine|Docetaxel & Gemcitabine]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdw562 Martin et al. 2017 (BELLE-4)]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Buparlisib_.26_Paclitaxel_99|Buparlisib & Paclitaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #2, 80 mg/m<sup>2</sup> 3 weeks out of 4 {{#subobject:b70577|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00411-8 Takashima et al. 2015 (SELECT BC)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#S-1_monotherapy|S-1]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior OS
 
−
| style="background-color:#d73027" |Inferior EQ-5D score
 
−
|-
 
−
|[https://www.nature.com/articles/s41416-019-0391-z Fujiwara et al. 2019 (A3105301)]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#NK105_monotherapy_77|NK105]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS
 
−
| style="background-color:#d73027" |Higher rate of CIPN
 
−
|-
 
−
|}
 
−
''Note: this is the lower limit of dosing allowed in SELECT BC.''
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #3, 90 mg/m<sup>2</sup> 3 weeks out of 4 {{#subobject:1a1adf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa072113 Miller et al. 2007 (ECOG E2100)]
 
−
|2001-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(16)32470-4 Miles et al. 2016 (MERiDiAN)]
 
−
|2012-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 90 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #4, 100 mg/m<sup>2</sup> weekly {{#subobject:f8eb25|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1998.16.10.3353 Seidman et al. 1998]
 
−
|NR
 
−
| style="background-color:#ffffbe" |Phase 2, less than 20 pts in this subgroup
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #5, 100 mg/m<sup>2</sup> 3 weeks out of 4 {{#subobject:1a1adf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00411-8 Takashima et al. 2015 (SELECT BC)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#S-1_monotherapy|S-1]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior OS
 
−
| style="background-color:#d73027" |Inferior EQ-5D score
 
−
|-
 
−
|}
 
−
''Note: this is the upper limit of dosing allowed in SELECT BC.''
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# Seidman AD, Hudis CA, Albanell J, Tong W, Tepler I, Currie V, Moynahan ME, Theodoulou M, Gollub M, Baselga J, Norton L. Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol. 1998 Oct;16(10):3353-61. Erratum in: J Clin Oncol. 2006 May 10;24(14):2220. Albanel, J [corrected to Albanell, J ]. [https://doi.org/10.1200/JCO.1998.16.10.3353 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9779712 PubMed]
 
−
# Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001 Nov 15;19(22):4216-23. [https://doi.org/10.1200/jco.2001.19.22.4216 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11709565 PubMed]
 
−
# '''ECOG E2100:''' Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76. [https://doi.org/10.1056/NEJMoa072113 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18160686 PubMed] NCT00028990
 
−
<!-- Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA. -->
 
−
# '''CALGB 9840:''' Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. [https://doi.org/10.1200/jco.2007.11.6699 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18375893 PubMed] NCT00003440
 
−
# Fountzilas G, Dafni U, Dimopoulos MA, Koutras A, Skarlos D, Papakostas P, Gogas H, Bafaloukos D, Kalogera-Fountzila A, Samantas E, Briasoulis E, Pectasides D, Maniadakis N, Matsiakou F, Aravantinos G, Papadimitriou C, Karina M, Christodoulou C, Kosmidis P, Kalofonos HP; Hellenic Cooperative Oncology Group. A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer: a Hellenic Cooperative Oncology Group study. Breast Cancer Res Treat. 2009 May;115(1):87-99. Epub 2008 May 16. [https://doi.org/10.1007/s10549-008-0047-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18483853 PubMed]
 
−
# '''SELECT BC:''' Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. Epub 2015 Nov 27. [https://doi.org/10.1016/S1470-2045(15)00411-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26617202 PubMed] UMIN C000000416
 
−
## '''HRQoL analysis:''' Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Doihara H, Akabane H, Kashiwaba M, Watanabe T, Ohashi Y, Mukai H. Long-term health status as measured by EQ-5D among patients with metastatic breast cancer: comparison of first-line oral S-1 and taxane therapies in the randomized phase III SELECT BC trial. Qual Life Res. 2017 Feb;26(2):445-453. Epub 2016 Aug 12. [https://doi.org/10.1007/s11136-016-1388-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27517267 PubMed]
 
−
# '''MERiDiAN:''' Miles D, Cameron D, Bondarenko I, Manzyuk L, Alcedo JC, Lopez RI, Im SA, Canon JL, Shparyk Y, Yardley DA, Masuda N, Ro J, Denduluri N, Hubeaux S, Quah C, Bais C, O'Shaughnessy J. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer. 2017 Jan;70:146-155. Epub 2016 Nov 4. [https://www.ejcancer.com/article/S0959-8049(16)32470-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27817944 PubMed] NCT01663727
 
−
## '''Update:''' Miles D, Cameron D, Hilton M, Garcia J, O'Shaughnessy J. Overall survival in MERiDiAN, a double-blind placebo-controlled randomised phase III trial evaluating first-line bevacizumab plus paclitaxel for HER2-negative metastatic breast cancer. Eur J Cancer. 2018 Feb;90:153-155. Epub 2017 Nov 23. [https://www.ejcancer.com/article/S0959-8049(17)31358-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29174181 PubMed]
 
−
# '''BELLE-4:''' Martín M, Chan A, Dirix L, O'Shaughnessy J, Hegg R, Manikhas A, Shtivelband M, Krivorotko P, Batista López N, Campone M, Ruiz Borrego M, Khan QJ, Beck JT, Ramos Vázquez M, Urban P, Goteti S, Di Tomaso E, Massacesi C, Delaloge S. A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4). Ann Oncol. 2017 Feb 1;28(2):313-320. [https://doi.org/10.1093/annonc/mdw562 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27803006 PubMed] NCT01572727
 
−
# '''A3105301:''' Fujiwara Y, Mukai H, Saeki T, Ro J, Lin YC, Nagai SE, Lee KS, Watanabe J, Ohtani S, Kim SB, Kuroi K, Tsugawa K, Tokuda Y, Iwata H, Park YH, Yang Y, Nambu Y. A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients. Br J Cancer. 2019 Mar;120(5):475-480. Epub 2019 Feb 12. [https://www.nature.com/articles/s41416-019-0391-z link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30745582 PubMed] NCT01644890
 
−
 
 
−
==Paclitaxel monotherapy, q3wk {{#subobject:3e5448|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, 175 mg/m<sup>2</sup> q3wk {{#subobject:72389a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1995.13.10.2575 Seidman et al. 1995]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.08.048 Winer et al. 2004 (CALGB 9342)]
 
−
|1994-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]; 210 mg/m<sup>2</sup> q3wk<br> 2. [[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]; 250 mg/m<sup>2</sup> q3wk
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.11.6699 Seidman et al. 2008 (CALGB 9840)]
 
−
|1998-NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_monotherapy.2C_weekly_2|Paclitaxel]]; weekly
 
−
| style="background-color:#d73027" |Inferior OS
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.11.9362 Albain et al. 2008]
 
−
|1999-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Gemcitabine_.26_Paclitaxel|GT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.04.937 Gradishar et al. 2005 (CA012-0)]
 
−
|2001-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#nab-Paclitaxel_monotherapy_2|nab-Paclitaxel]]
 
−
| style="background-color:#d73027" |Inferior TTP
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651098/ Di Leo et al. 2008 (EGF30001)]
 
−
|2004-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Lapatinib_.26_Paclitaxel_99|Lapatinib & Paclitaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
| style="background-color:#1a9850" |Less toxic
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00411-8 Takashima et al. 2015 (SELECT BC)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#S-1_monotherapy|S-1]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior OS
 
−
| style="background-color:#d73027" |Inferior EQ-5D score
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512366/ Park et al. 2016 (GPMBC301)]
 
−
|2008-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_polymeric_micelle_formulation_monotherapy_88|Genexol-PM]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior ORR
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''Note: patients in EGF30001 were NOT required to be HER2-positive.''
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #2, 175 mg/m<sup>2</sup>, CI {{#subobject:e67gb7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.2003.08.013 Sledge et al. 2003 (ECOG E1193)]
 
−
|rowspan=2|1993-1995
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Doxorubicin_.26_Paclitaxel_.28AT.29_2|AT (Taxol)]]
 
−
| style="background-color:#d73027" |Inferior TTF
 
−
|-
 
−
|2. [[#Doxorubicin_monotherapy_2|Doxorubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #3, 175 mg/m<sup>2</sup> q4wk {{#subobject:42c791|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00411-8 Takashima et al. 2015 (SELECT BC)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#S-1_monotherapy|S-1]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior OS
 
−
| style="background-color:#d73027" |Inferior EQ-5D score
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #4, 200 mg/m<sup>2</sup> {{#subobject:2e25d1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1999.17.8.2355 Bishop et al. 1999]
 
−
|1993-NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[Breast_cancer_-_historical#CMFP_2|CMFP]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.4.724 Paridaens et al. 2000 (EORTC 10923)]
 
−
|1993-1996
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Doxorubicin_monotherapy_2|Doxorubicin]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
 
−
'''21-day cycle for 7 or 8 cycles'''
 
−
 
 
−
===Regimen variant #5, 250 mg/m<sup>2</sup> {{#subobject:e60257|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/jnci/83.24.1797-a Holmes et al. 1991]
 
−
|1990
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1999.17.11.3403 Smith et al. 1996 (NSABP B-26)]
 
−
|1994-1996
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]; 250 mg/m<sup>2</sup> over 3 hours
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: Holmes et al. 1991 is of historic interest, being the first phase II trial of a taxane in breast cancer.''
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 250 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# Holmes FA, Walters RS, Theriault RL, Forman AD, Newton LK, Raber MN, Buzdar AU, Frye DK, Hortobagyi GN. Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst. 1991 Dec 18;83(24):1797-805. [https://doi.org/10.1093/jnci/83.24.1797-a link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1683908 PubMed]
 
−
# Seidman AD, Tiersten A, Hudis C, Gollub M, Barrett S, Yao TJ, Lepore J, Gilewski T, Currie V, Crown J, Hakes T, Baselga J, Sklarin N, Moynihan ME, Tong W, Egorin M, Kearns C, Spriggs D, Norton L. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol. 1995 Oct;13(10):2575-81. [https://doi.org/10.1200/jco.1995.13.10.2575 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7595709 PubMed]
 
−
# Bishop JF, Dewar J, Toner GC, Smith J, Tattersall MH, Olver IN, Ackland S, Kennedy I, Goldstein D, Gurney H, Walpole E, Levi J, Stephenson J, Canetta R. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2355-64. [https://doi.org/10.1200/JCO.1999.17.8.2355 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10561297 PubMed]
 
−
# '''NSABP B-26:''' Smith RE, Brown AM, Mamounas EP, Anderson SJ, Lembersky BC, Atkins JH, Shibata HR, Baez L, DeFusco PA, Davila E, Tipping SJ, Bearden JD, Thirlwell MP. Randomized trial of 3-hour versus 24-hour infusion of high-dose paclitaxel in patients with metastatic or locally advanced breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-26. J Clin Oncol. 1999 Nov;17(11):3403-11. [https://doi.org/10.1200/JCO.1999.17.11.3403 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10550134 PubMed]
 
−
# '''EORTC 10923:''' Paridaens R, Biganzoli L, Bruning P, Klijn JG, Gamucci T, Houston S, Coleman R, Schachter J, Van Vreckem A, Sylvester R, Awada A, Wildiers J, Piccart M. Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organisation for Research and Treatment of Cancer Randomized Study with cross-over. J Clin Oncol. 2000 Feb;18(4):724-33. [https://doi.org/10.1200/JCO.2000.18.4.724 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10673513 PubMed]
 
−
## '''HRQoL analysis:''' Kramer JA, Curran D, Piccart M, de Haes JC, Bruning PF, Klijn JG, Bontenbal M, van Pottelsberghe C, Groenvold M, Paridaens R. Randomised trial of paclitaxel versus doxorubicin as first-line chemotherapy for advanced breast cancer: quality of life evaluation using the EORTC QLQ-C30 and the Rotterdam symptom checklist. Eur J Cancer. 2000 Aug;36(12):1488-97. [https://www.ejcancer.com/article/S0959-8049(00)00134-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10930796 PubMed]
 
−
# '''ECOG E1193:''' Sledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK, Wood WC. Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2003 Feb 15;21(4):588-92. [https://doi.org/10.1200/JCO.2003.08.013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12586793 PubMed]
 
−
# '''CALGB 9342:''' Winer EP, Berry DA, Woolf S, Duggan D, Kornblith A, Harris LN, Michaelson RA, Kirshner JA, Fleming GF, Perry MC, Graham ML, Sharp SA, Keresztes R, Henderson IC, Hudis C, Muss H, Norton L. Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: Cancer and Leukemia Group B trial 9342. J Clin Oncol. 2004 Jun 1;22(11):2061-8. [https://doi.org/10.1200/JCO.2004.08.048 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15169793 PubMed]
 
−
<!-- Presented in part at the 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003. -->
 
−
# '''CA012-0:''' Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. Epub 2005 Sep 19. [https://doi.org/10.1200/jco.2005.04.937 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16172456 PubMed] NCT00046527
 
−
<!-- Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA. -->
 
−
# '''CALGB 9840:''' Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. [https://doi.org/10.1200/jco.2007.11.6699 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18375893 PubMed] NCT00003440
 
−
<!-- Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003, and the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004. -->
 
−
# Albain KS, Nag SM, Calderillo-Ruiz G, Jordaan JP, Llombart AC, Pluzanska A, Rolski J, Melemed AS, Reyes-Vidal JM, Sekhon JS, Simms L, O'Shaughnessy J. Gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol. 2008 Aug 20;26(24):3950-7. [https://doi.org/10.1200/jco.2007.11.9362 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18711184 PubMed]
 
−
# '''EGF30001:''' Di Leo A, Gomez HL, Aziz Z, Zvirbule Z, Bines J, Arbushites MC, Guerrera SF, Koehler M, Oliva C, Stein SH, Williams LS, Dering J, Finn RS, Press MF. Phase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer. J Clin Oncol. 2008 Dec 1;26(34):5544-52. Epub 2008 Oct 27. Erratum in: J Clin Oncol. 2009 Apr 10;27(11):1923. [https://doi.org/10.1200/JCO.2008.16.2578 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651098/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18955454 PubMed] NCT00075270
 
−
# '''SELECT BC:''' Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. Epub 2015 Nov 27. [https://doi.org/10.1016/S1470-2045(15)00411-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26617202 PubMed] UMIN C000000416
 
−
## '''HRQoL analysis:''' Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Doihara H, Akabane H, Kashiwaba M, Watanabe T, Ohashi Y, Mukai H. Long-term health status as measured by EQ-5D among patients with metastatic breast cancer: comparison of first-line oral S-1 and taxane therapies in the randomized phase III SELECT BC trial. Qual Life Res. 2017 Feb;26(2):445-453. Epub 2016 Aug 12. [https://doi.org/10.1007/s11136-016-1388-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27517267 PubMed]
 
−
# '''GPMBC301:''' Park IH, Sohn JH, Kim SB, Lee KS, Chung JS, Lee SH, Kim TY, Jung KH, Cho EK, Kim YS, Song HS, Seo JH, Ryoo HM, Lee SA, Yoon SY, Kim CS, Kim YT, Kim SY, Jin MR, Ro J. An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer. Cancer Res Treat. 2017 Jul;49(3):569-577. Epub 2016 Sep 12. [https://doi.org/10.4143/crt.2016.289 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512366/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27618821 PubMed] NCT00876486
 
−
 
 
−
==Paclitaxel & Bevacizumab {{#subobject:ab5252|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:1c2f5c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa072113 Miller et al. 2007 (ECOG E2100)]
 
−
|2001-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Paclitaxel_monotherapy.2C_weekly_2|Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11.8 vs 5.9 mo<br>(HR 0.60)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617186/ Robert et al. 2011 (SUN 1094)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_.26_Sunitinib_99|Paclitaxel & Sunitinib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70566-1 Lang et al. 2013 (TURANDOT)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Capecitabine_.26_Bevacizumab|Capecitabine & Bevacizumab]]
 
−
| style="background-color:#eeee01" |Non-inferior OS<sup>1</sup>
 
−
|-
 
−
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500830/ Rugo et al. 2015 (CALGB 40502/NCCTG N063H)]
 
−
|rowspan=2|2008-2011
 
−
| rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Stub#Ixabepilone_.26_Bevacizumab|Ixabepilone & Bevacizumab]]
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|-
 
−
|2. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d9ef8b" |Might have superior PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5057418/ Rochlitz et al. 2016 (SAKK 24/09)]
 
−
|2010-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine.2C_Cyclophosphamide.2C_Bevacizumab_99|Capecitabine, Cyclophosphamide, Bevacizumab]]
 
−
| style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(16)32470-4 Miles et al. 2016 (MERiDiAN)]
 
−
|2012-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Paclitaxel_monotherapy.2C_weekly_2|Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11 vs 8.8 mo<br>(HR 0.68, 99% CI 0.51-0.91)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for TURANDOT is based on the 2016 update.''<br>
 
−
''Note: ECOG E2100 was the basis for accelerated approval of bevacizumab in breast cancer.''
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 90 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# '''ECOG E2100:''' Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76. [https://doi.org/10.1056/NEJMoa072113 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18160686 PubMed] NCT00028990
 
−
# '''SUN 1094:''' Robert NJ, Saleh MN, Paul D, Generali D, Gressot L, Copur MS, Brufsky AM, Minton SE, Giguere JK, Smith JW 2nd, Richards PD, Gernhardt D, Huang X, Liau KF, Kern KA, Davis J. Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial. Clin Breast Cancer. 2011 Apr;11(2):82-92. Epub 2011 Apr 11. Erratum in: Clin Breast Cancer. 2011 Aug;11(4):273. [https://www.clinical-breast-cancer.com/article/S1526-8209(11)00006-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617186/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21569994 PubMed] NCT00373256
 
−
# '''TURANDOT:''' Lang I, Brodowicz T, Ryvo L, Kahan Z, Greil R, Beslija S, Stemmer SM, Kaufman B, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Messinger D, Zielinski C; Central European Cooperative Oncology Group. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial. Lancet Oncol. 2013 Feb;14(2):125-33. Epub 2013 Jan 10. [https://doi.org/10.1016/S1470-2045(12)70566-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23312888 PubMed] NCT00600340
 
−
## '''Update:''' Zielinski C, Láng I, Inbar M, Kahán Z, Greil R, Beslija S, Stemmer SM, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Petruzelka L, Eniu A, Nisenbaum B, Dank M, Anghel R, Messinger D, Brodowicz T; TURANDOT investigators. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. Lancet Oncol. 2016 Sep;17(9):1230-9. Epub 2016 Aug 5. [https://doi.org/10.1016/S1470-2045(16)30154-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27501767 PubMed]
 
−
# '''CALGB 40502/NCCTG N063H:''' Rugo HS, Barry WT, Moreno-Aspitia A, Lyss AP, Cirrincione C, Leung E, Mayer EL, Naughton M, Toppmeyer D, Carey LA, Perez EA, Hudis C, Winer EP. Randomized phase III trial of paclitaxel once per week compared with nanoparticle albumin-bound nab-paclitaxel once per week or ixabepilone with bevacizumab as first-line chemotherapy for locally recurrent or metastatic breast cancer: CALGB 40502/NCCTG N063H (Alliance). J Clin Oncol. 2015 Jul 20;33(21):2361-9. Epub 2015 Jun 8. [https://doi.org/10.1200/JCO.2014.59.5298 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500830/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26056183 PubMed] NCT00785291
 
−
# '''SAKK 24/09:''' Rochlitz C, Bigler M, von Moos R, Bernhard J, Matter-Walstra K, Wicki A, Zaman K, Anchisi S, Küng M, Na KJ, Bärtschi D, Borner M, Rordorf T, Rauch D, Müller A, Ruhstaller T, Vetter M, Trojan A, Hasler-Strub U, Cathomas R, Winterhalder R; Swiss Group for Clinical Cancer Research (SAKK). SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial. BMC Cancer. 2016 Oct 10;16(1):780. [https://doi.org/10.1186/s12885-016-2823-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5057418/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27724870/ PubMed] NCT01131195
 
−
# '''MERiDiAN:''' Miles D, Cameron D, Bondarenko I, Manzyuk L, Alcedo JC, Lopez RI, Im SA, Canon JL, Shparyk Y, Yardley DA, Masuda N, Ro J, Denduluri N, Hubeaux S, Quah C, Bais C, O'Shaughnessy J. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer. 2017 Jan;70:146-155. Epub 2016 Nov 4. [https://www.ejcancer.com/article/S0959-8049(16)32470-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27817944 PubMed] NCT01663727
 
−
## '''Update:''' Miles D, Cameron D, Hilton M, Garcia J, O'Shaughnessy J. Overall survival in MERiDiAN, a double-blind placebo-controlled randomised phase III trial evaluating first-line bevacizumab plus paclitaxel for HER2-negative metastatic breast cancer. Eur J Cancer. 2018 Feb;90:153-155. Epub 2017 Nov 23. [https://www.ejcancer.com/article/S0959-8049(17)31358-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29174181 PubMed]
 
−
 
 
−
==Paclitaxel & Vinorelbine {{#subobject:ab6465|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:1c8hcc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1999.17.1.74 Romero Acuña et al. 1999]
 
−
|1995-1997
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second'''
 
−
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV over 20 minutes once per day on days 1 & 8
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# Romero Acuña L, Langhi M, Pérez J, Romero Acuña J, Machiavelli M, Lacava J, Vallejo C, Romero A, Fasce H, Ortiz E, Grasso S, Amato S, Rodríguez R, Barbieri M, Leone B. Vinorelbine and paclitaxel as first-line chemotherapy in metastatic breast cancer. J Clin Oncol. 1999 Jan;17(1):74-81. [https://doi.org/10.1200/JCO.1999.17.1.74 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10458220 PubMed]
 
−
 
 
−
==nab-Paclitaxel monotherapy {{#subobject:5dc417|Regimen=1}}==
 
−
 
 
−
===Example orders===
 
−
*[[Example orders for Paclitaxel, nanoparticle albumin-bound (Abraxane) in breast cancer]]
 
−
 
 
−
===Regimen variant #1, 100 mg/m<sup>2</sup>, 3 weeks out of 4 {{#subobject:f0096c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2008.18.5397 Gradishar et al. 2009]
 
−
|2005-2006
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
−
|1. [[#Docetaxel_monotherapy_2|Docetaxel]]<br> 2. [[#nab-Paclitaxel_monotherapy_2|nab-Paclitaxel]]; weekly, 150 mg/m<sup>2</sup><br> 3. [[#nab-Paclitaxel_monotherapy_2|nab-Paclitaxel]]; q3wk
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #2, 150 mg/m<sup>2</sup> weekly, 3 weeks out of 4 {{#subobject:f0096c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2008.18.5397 Gradishar et al. 2009]
 
−
|2005-2006
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
−
|1. [[#Docetaxel_monotherapy_2|Docetaxel]]<br> 2. [[#nab-Paclitaxel_monotherapy_2|nab-Paclitaxel]]; weekly, 100 mg/m<sup>2</sup><br> 3. [[#nab-Paclitaxel_monotherapy_2|nab-Paclitaxel]]; q3wk
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 150 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #3, 260 mg/m<sup>2</sup> q3wk {{#subobject:bf6371|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.04.937 Gradishar et al. 2005 (CA012-0)]
 
−
|2001-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]; q3wk
 
−
| style="background-color:#1a9850" |Superior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 260 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*CA012-0: No corticosteroid or antihistamine premedication
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #4, 300 mg/m<sup>2</sup> q3wk {{#subobject:11b87e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2008.18.5397 Gradishar et al. 2009]
 
−
|2005-2006
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
−
|1. [[#Docetaxel_monotherapy_2|Docetaxel]]<br> 2. [[#nab-Paclitaxel_monotherapy_2|nab-Paclitaxel]]; weekly, 100 mg/m<sup>2</sup><br> 3. [[#nab-Paclitaxel_monotherapy_2|nab-Paclitaxel]]; weekly, 150 mg/m<sup>2</sup>
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 300 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
<!-- Presented in part at the 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003. -->
 
−
# '''CA012-0:''' Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. Epub 2005 Sep 19. [https://doi.org/10.1200/jco.2005.04.937 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16172456 PubMed] NCT00046527
 
−
<!-- Presented in part at the 29th Annual San Antonio Breast Cancer Symposium, December 14-17, 2006, San Antonio, TX; the 43rd Annual Meeting of the American Society for Clinical Oncology, June 1-5, 2007, Chicago, IL; the 14th European Cancer Conference, September 23-27, 2007, Barcelona, Spain; and the 6th European Breast Cancer Conference, April 15-19, 2008, Berlin, Germany. -->
 
−
# Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009 Aug 1;27(22):3611-9. Epub 2009 May 26. Erratum in: J Clin Oncol. 2011 Jul 1;29(19):2739. [https://doi.org/10.1200/jco.2008.18.5397 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19470941 PubMed]
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
 
 
−
==Paclitaxel, nanoparticle albumin-bound & Bevacizumab {{#subobject:17e71f|Regimen=1}}==
 
−
 
 
−
===Example orders===
 
−
*[[Example orders for Paclitaxel, nanoparticle albumin-bound & Bevacizumab in breast cancer]]
 
−
 
 
−
===Regimen variant #1, 150 mg/m<sup>2</sup>, 3 weeks out of 4 {{#subobject:1fce34|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500830/ Rugo et al. 2015 (CALGB 40502/NCCTG N063H)]
 
−
|rowspan=2|2008-2011
 
−
| rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[Stub#Ixabepilone_.26_Bevacizumab|Ixabepilone & Bevacizumab]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#fee08b" |Might have inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 150 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #2, 260 mg/m<sup>2</sup> q3wk {{#subobject:8ded2a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#nab-Paclitaxel_monotherapy_2|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS <br>(HR 0.64, 95% CI 0.52-0.80)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 260 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
<!-- # '''Abstract:''' M. A. Danso, J. L. Blum, N. J. Robert, L. Krekow, R. Rotche, D. A. Smith, P. Richards, T. Anderson, D. A. Richards and J. O'Shaughnessy. Phase II trial of weekly nab-paclitaxel in combination with bevacizumab as first-line treatment in metastatic breast cancer. 2008 ASCO Annual Meeting abstract 1075. [http://meeting.ascopubs.org/cgi/content/abstract/26/15_suppl/1075 link to abstract] -->
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
# '''CALGB 40502/NCCTG N063H:''' Rugo HS, Barry WT, Moreno-Aspitia A, Lyss AP, Cirrincione C, Leung E, Mayer EL, Naughton M, Toppmeyer D, Carey LA, Perez EA, Hudis C, Winer EP. Randomized phase III trial of paclitaxel once per week compared with nanoparticle albumin-bound nab-paclitaxel once per week or ixabepilone with bevacizumab as first-line chemotherapy for locally recurrent or metastatic breast cancer: CALGB 40502/NCCTG N063H (Alliance). J Clin Oncol. 2015 Jul 20;33(21):2361-9. Epub 2015 Jun 8. [https://doi.org/10.1200/JCO.2014.59.5298 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500830/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26056183 PubMed] NCT00785291
 
−
 
 
−
==Pemetrexed monotherapy {{#subobject:93e4ed|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, 500 mg/m<sup>2</sup> {{#subobject:b49e6b|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/12/3/832.long Gomez et al. 2006]
 
−
|2001-2002
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
 
−
''Patients in the study were "chemotherapy-naïve, with advanced (T4 and N0-N2, M0, M1) breast cancer."''
 
−
====Chemotherapy====
 
−
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Dexamethasone (Decadron)]] 4 mg PO twice per day on days -1 to 2 (3 days)
 
−
*[[Folic acid (Folate)]] 350 to 1000 mcg PO once per day, to start 5 to 7 days prior to start of [[Pemetrexed (Alimta)]], to continue throughout therapy
 
−
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, the first dose given before the study's pretreatment biopsy, to continue throughout therapy
 
−
 
 
−
'''21-day cycle for up to 3 cycles'''
 
−
 
 
−
===Regimen variant #2, 600 mg/m<sup>2</sup> {{#subobject:a2f6d|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-010-1286-0 Robert et al. 2011]
 
−
|2005-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Pemetrexed (Alimta)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
====Supportive therapy====
 
−
*[[Dexamethasone (Decadron)]] 4 mg PO twice per day on days -1 to 2 (3 days)
 
−
*[[Folic acid (Folate)]] 350 to 1000 mcg PO once per day, to start at least 5 days prior to start of [[Pemetrexed (Alimta)]], to continue throughout therapy, and until 3 weeks after the last dose of pemetrexed
 
−
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 8 to 10 weeks, the first dose given at least 1 week prior to start of [[Pemetrexed (Alimta)]], to continue throughout therapy, and until 3 weeks after the last dose of pemetrexed
 
−
 
 
−
'''14-day cycles'''
 
−
===References===
 
−
# Gomez HL, Santillana SL, Vallejos CS, Velarde R, Sanchez J, Wang X, Bauer NL, Hockett RD, Chen VJ, Niyikiza C, Hanauske AR. A phase II trial of pemetrexed in advanced breast cancer: clinical response and association with molecular target expression. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):832-8. [http://clincancerres.aacrjournals.org/content/12/3/832.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16467096 PubMed]
 
−
# Robert NJ, Conkling PR, O'Rourke MA, Kuefler PR, McIntyre KJ, Zhan F, Asmar L, Wang Y, Shonukan OO, O'Shaughnessy JA. Results of a phase II study of pemetrexed as first-line chemotherapy in patients with advanced or metastatic breast cancer. Breast Cancer Res Treat. 2011 Feb;126(1):101-8. Epub 2010 Dec 25. [https://doi.org/10.1007/s10549-010-1286-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21188632 PubMed]
 
−
 
 
−
==S-1 monotherapy {{#subobject:7702f2|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:48e547|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00411-8 Takashima et al. 2015 (SELECT BC)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Docetaxel_monotherapy_2|Docetaxel]]<br> 2. [[#Paclitaxel_monotherapy.2C_weekly_2|Paclitaxel]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior OS
 
−
| style="background-color:#1a9850" |Superior EQ-5D score
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548517/ Mukai et al. 2021 (SELECT BC-CONFIRM)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_3|AC]]<br>2. [[#FAC_3|FAC]]<br>3. [[#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]]<br>4. [[#FEC_3|FEC]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
 
−
**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28
 
−
**BSA at least 1.25 m<sup>2</sup> and less than 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 28
 
−
**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 28
 
−
 
 
−
'''42-day cycles'''
 
−
 
 
−
===References===
 
−
# '''SELECT BC:''' Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. Epub 2015 Nov 27. [https://doi.org/10.1016/S1470-2045(15)00411-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26617202 PubMed] UMIN C000000416
 
−
## '''HRQoL analysis:''' Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Doihara H, Akabane H, Kashiwaba M, Watanabe T, Ohashi Y, Mukai H. Long-term health status as measured by EQ-5D among patients with metastatic breast cancer: comparison of first-line oral S-1 and taxane therapies in the randomized phase III SELECT BC trial. Qual Life Res. 2017 Feb;26(2):445-453. Epub 2016 Aug 12. [https://doi.org/10.1007/s11136-016-1388-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27517267 PubMed]
 
−
# '''SELECT BC-CONFIRM:''' Mukai H, Uemura Y, Akabane H, Watanabe T, Park Y, Takahashi M, Sagara Y, Nishimura R, Takashima T, Fujisawa T, Hozumi Y, Kawahara T. Anthracycline-containing regimens or taxane versus S-1 as first-line chemotherapy for metastatic breast cancer. Br J Cancer. 2021 Oct;125(9):1217-1225. Epub 2021 Sep 3. [https://doi.org/10.1038/s41416-021-01531-6 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548517/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34480096/ PubMed] UMIN000005449
 
−
 
 
−
==Capecitabine & Docetaxel (TX) {{#subobject:9d5b30|Regimen=1}}==
 
−
 
 
−
TX: '''<u>T</u>'''axotere (Docetaxel) & '''<u>X</u>'''eloda (Capecitabine)
 
−
<br>CD: '''<u>C</u>'''apecitabine & '''<u>D</u>'''ocetaxel
 
−
===Regimen variant #1, 1900/75 {{#subobject:acuqib|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdp498 Mavroudis et al. 2009 (HORG CT/02.09)]
 
−
|2002-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Docetaxel_.26_Epirubicin_.28DE.29_2|DE]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 950 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #2, 2000/75, limited duration of docetaxel {{#subobject:acd1c7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.29492 Wang et al. 2015 (ML25241)]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#Capecitabine_.26_Vinorelbine|NX]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS
 
−
|-
 
−
|}
 
−
''Note: only patients without progression proceeded to the capecitabine maintenance phase.''
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycles 1 to 6 up to 8: 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #3, 2000/75, indefinite {{#subobject:ad8cc7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdq578 Seidman et al. 2010 (B9E-MC-S273)]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Gemcitabine|GD]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
====Subsequent treatment====
 
−
*Upon progression: [[#Gemcitabine_monotherapy_2|Gemcitabine]]
 
−
 
 
−
===References===
 
−
# '''HORG CT/02.09:''' Mavroudis D, Papakotoulas P, Ardavanis A, Syrigos K, Kakolyris S, Ziras N, Kouroussis C, Malamos N, Polyzos A, Christophyllakis C, Kentepozidis N, Georgoulias V; Hellenic Oncology Research Group. Randomized phase III trial comparing docetaxel plus epirubicin versus docetaxel plus capecitabine as first-line treatment in women with advanced breast cancer. Ann Oncol. 2010 Jan;21(1):48-54. Epub 2009 Nov 11. [https://doi.org/10.1093/annonc/mdp498 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19906761 PubMed] NCT00429871
 
−
# '''B9E-MC-S273:''' Seidman AD, Brufsky A, Ansari RH, Hart LL, Stein RS, Schwartzberg LS, Stewart JF, Russell CA, Chen SC, Fein LE, De La Cruz Vargas JA, Kim SB, Cavalheiro J, Zhao L, Gill JF, Obasaju CK, Orlando M, Tai DF. Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel with planned crossover to the alternate single agent in metastatic breast cancer. Ann Oncol. 2011 May;22(5):1094-101. Epub 2010 Nov 17. [https://doi.org/10.1093/annonc/mdq578 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21084429 PubMed] NCT00191438
 
−
## '''Pooled update:''' Seidman AD, Chan S, Wang J, Zhu C, Xu C, Xu B. A pooled analysis of gemcitabine plus docetaxel versus capecitabine plus docetaxel in metastatic breast cancer. Oncologist. 2014 May;19(5):443-52. Epub 2014 Apr 4. [https://doi.org/10.1634/theoncologist.2013-0428 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4012969/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24705980/ PubMed]
 
−
# '''ML25241:''' Wang J, Xu B, Yuan P, Ma F, Li Q, Zhang P, Cai R, Fan Y, Luo Y, Li Q. Capecitabine combined with docetaxel versus vinorelbine followed by capecitabine maintenance medication for first-line treatment of patients with advanced breast cancer: phase 3 randomized trial. Cancer. 2015 Oct 1;121(19):3412-21. Epub 2015 Jun 19. [https://doi.org/full/10.1002/cncr.29492 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26096296 PubMed] NCT01126138
 
−
 
 
−
==Epirubicin & Vinorelbine (VE) {{#subobject:e329f2|Regimen=1}}==
 
−
 
 
−
VE: '''<u>V</u>'''inorelbine & '''<u>E</u>'''pirubicin
 
−
===Regimen {{#subobject:ea3na6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.11.503 Ejlertsen et al. 2004 (SBG 9403)]
 
−
|1995-1999
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Epirubicin_monotherapy_2|Epirubicin]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycle for up to 18 cycles (1 year)'''
 
−
===References===
 
−
# '''SBG 9403:''' Ejlertsen B, Mouridsen HT, Langkjer ST, Andersen J, Sjöström J, Kjaer M; Scandinavian Breast Group. Phase III study of intravenous vinorelbine in combination with epirubicin versus epirubicin alone in patients with advanced breast cancer: a Scandinavian Breast Group Trial (SBG9403). J Clin Oncol. 2004 Jun 15;22(12):2313-20. [https://doi.org/10.1200/JCO.2004.11.503 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15197192 PubMed]
 
−
 
 
−
=Metastatic disease, maintenance after first-line therapy=
 
−
==Bevacizumab monotherapy {{#subobject:0e6349|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:f64795|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.0982 Robert et al. 2011 (RIBBON-1)]
 
−
|2005-2007
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2008.21.6457 Miles et al. 2010 (AVADO)]
 
−
|2006-2007
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70444-9 Gligorov et al. 2014 (IMELDA)]
 
−
|2009-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Bevacizumab_2|Capecitabine & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*AVADO: [[#Docetaxel_.26_Bevacizumab|Docetaxel & Bev]] x 9
 
−
*RIBBON-1: [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_.26_Bevacizumab_2|AC & Bev]] x 8 or [[#Cyclophosphamide_.26_Epirubicin_.28EC.29_.26_Bevacizumab|EC & Bev]] x 8 or [[#FAC_.26_Bevacizumab|FAC & Bev]] x 8 or [[#FEC_.26_Bevacizumab|FEC & Bev]] x 8
 
−
*IMELDA: [[#Docetaxel_.26_Bevacizumab|Docetaxel & Bev]] x 3 to 6
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
===References===
 
−
# '''AVADO:''' Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3239-47. Epub 2010 May 24. [https://doi.org/10.1200/JCO.2008.21.6457 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20498403 PubMed] NCT00333775
 
−
<!-- Presented in part at the 45th Annual Meeting of the American Society for Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany. -->
 
−
# '''RIBBON-1:''' Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. [https://doi.org/10.1200/JCO.2010.28.0982 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21383283 PubMed] NCT00262067
 
−
# '''IMELDA:''' Gligorov J, Doval D, Bines J, Alba E, Cortes P, Pierga JY, Gupta V, Costa R, Srock S, de Ducla S, Freudensprung U, Mustacchi G. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1351-60. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70444-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25273343 PubMed] NCT00929240
 
−
 
 
−
==Capecitabine & Bevacizumab {{#subobject:hca349|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:f67gcjc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70444-9 Gligorov et al. 2014 (IMELDA)]
 
−
|2009-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Bevacizumab_monotherapy_2|Bevacizumab]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 39 vs 23.7 mo<br>(HR 0.43, 95% CI 0.26-0.69)
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[#Docetaxel_.26_Bevacizumab|Docetaxel & Bev]] x 3 to 6
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
===References===
 
−
# '''IMELDA:''' Gligorov J, Doval D, Bines J, Alba E, Cortes P, Pierga JY, Gupta V, Costa R, Srock S, de Ducla S, Freudensprung U, Mustacchi G. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1351-60. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70444-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25273343 PubMed] NCT00929240
 
−
 
 
−
==Gemcitabine & Paclitaxel {{#subobject:a86e9e|Regimen=1}}==
 
−
 
 
−
GT: '''<u>G</u>'''emcitabine & '''<u>T</u>'''axol (Paclitaxel)
 
−
<br>PG: '''<u>P</u>'''aclitaxel & '''<u>G</u>'''emcitabine
 
−
===Regimen {{#subobject:19fc21|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.45.2490 Park et al. 2013 (KCSG-BR07-02)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation_2|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 32.3 vs 23.5 mo<br>(HR 0.65, 95% CI 0.42-0.99)
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[#Gemcitabine_.26_Paclitaxel|PG]] x 6
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given second on day 1'''
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1, '''given first'''
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# '''KCSG-BR07-02:''' Park YH, Jung KH, Im SA, Sohn JH, Ro J, Ahn JH, Kim SB, Nam BH, Oh DY, Han SW, Lee S, Park IH, Lee KS, Kim JH, Kang SY, Lee MH, Park HS, Ahn JS, Im YH. Phase III, multicenter, randomized trial of maintenance chemotherapy versus observation in patients with metastatic breast cancer after achieving disease control with six cycles of gemcitabine plus paclitaxel as first-line chemotherapy: KCSG-BR07-02. J Clin Oncol. 2013 May 10;31(14):1732-9. Epub 2013 Apr 8. [https://doi.org/10.1200/JCO.2012.45.2490 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23569309 PubMed] NCT00561119
 
−
 
 
−
=Metastatic disease, subsequent lines of chemotherapy=
 
−
==Capecitabine monotherapy {{#subobject:bd9beb|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, 1000 mg/m<sup>2</sup> PO twice per day {{#subobject:4eb6c8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br> 2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br> 3. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br> 4. [[#Paclitaxel_.26_Bevacizumab_2|Paclitaxel & Bevacizumab]]<br> 5. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]] <br> 6. [[#Vinorelbine_.26_Bevacizumab|Vinorelbine & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855860/ Barrios et al. 2010 (SUN 1107)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Sunitinib_monotherapy_99|Sunitinib]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 4.2 vs 2.8 mo<br>(HR 0.68, 95% CI 0.53-0.86)
 
−
|
 
−
|-
 
−
|[https://www.clinical-breast-cancer.com/article/S1526-8209(17)30005-8 Baselga et al. 2017 (RESILIENCE)]
 
−
|2010-NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Sorafenib_99|Capecitabine & Sorafenib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 5.4 vs 5.5 mo<br>(HR 1.03, 95% CI 0.82-1.28)
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2203690 Modi et al. 2022 (DESTINY-Breast04)]
 
−
|2018-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|
 
−
|-
 
−
|Awaiting publication (TROPiCS-02)
 
−
|2019-2024
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Sacituzumab_govitecan_monotherapy_66|Sacituzumab govitecan]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
| style="background-color:#d73027" |Faster deterioration of global QoL
 
−
|-
 
−
|}
 
−
''Note: in SUN 1107, this dosage was used for patients older than 65 years. This was the lower bound of dosing in DESTINY-Breast04 & TROPiCS-02.''
 
−
====Prior treatment criteria====
 
−
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
 
−
====Biomarker eligibility criteria====
 
−
*DESTINY-Breast04: HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
 
−
*TROPiCS-02: HR+
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #2, 1250 mg/m<sup>2</sup> PO twice per day {{#subobject:f3e92c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1999.17.2.485 Blum et al. 1999]
 
−
|1996
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdg346 Reichardt et al. 2003]
 
−
|1999-2000
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.05.098 Miller et al. 2005 (AVF2119g)]
 
−
|2000-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdr405 Pallis et al. 2011 (HORG CT/02.11)]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Gemcitabine_.26_Vinorelbine_99|Gemcitabine & Vinorelbine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 5.2 vs 5.4 mo
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.12.6557 Thomas et al. 2007 (CA163-046)]
 
−
|2003-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Ixabepilone|Capecitabine & Ixabepilone]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903325/ Sparano et al. 2010 (CA163-048)]
 
−
|2003-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Ixabepilone|Capecitabine & Ixabepilone]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855860/ Barrios et al. 2010 (SUN 1107)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Sunitinib_monotherapy_99|Sunitinib]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 4.2 vs 2.8 mo<br>(HR 0.68, 95% CI 0.53-0.86)
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463422/ Kaufman et al. 2015 (E7389-G000-301)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Eribulin_monotherapy|Eribulin]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.43.3391 Crown et al. 2013 (A6181099)]
 
−
|2007-2009 (C)
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Sunitinib_99|Capecitabine & Sunitinib]]
 
−
| style="background-color:#d9ef8b" |Might have superior PFS<br>Median PFS: 5.9 vs 5.5 mo<br>(HR 0.82, 95% CI 0.63-1.05)
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-016-4075-6 Yamamoto et al. 2016 (JO21095)]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdy063 Martin et al. 2018 (L00070 IN 305 B0)]
 
−
|2009-2011 (C)
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Vinflunine|Capecitabine & Vinflunine]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333992/ Park et al. 2018 (PROCEED)]
 
−
|2011-2016 (C)
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CAPIRI_99|IX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 4.7 vs 6.4 mo
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(17)30088-8 Zhang et al. 2017 (BG01-1323L)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Utidelone_77|Capecitabine & Utidelone]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2203690 Modi et al. 2022 (DESTINY-Breast04)]
 
−
|2018-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|
 
−
|-
 
−
|Awaiting publication (TROPiCS-02)
 
−
|2019-2024
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Sacituzumab_govitecan_monotherapy_66|Sacituzumab govitecan]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
| style="background-color:#d73027" |Faster deterioration of global QoL
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for BG01-1323L is based on the 2020 update.''<br>
 
−
''Note: To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm in this context. This was the upper bound of dosing in DESTINY-Breast04 & TROPiCS-02.''
 
−
====Prior treatment criteria====
 
−
*Blum et al. 1999: Exposure to paclitaxel and an anthracycline
 
−
*Reichardt et al. 2003: Exposure to a [[Regimen_classes#Taxane-based_regimen|taxane-containing regimen]]
 
−
*AVF2119g, HORG CT/02.11, CA163-046, CA163-048, SUN 1107, E7389-G000-301, A6181099, L00070 IN 305 B0, PROCEED, BG01-1323L: Exposure to a taxane and an anthracycline
 
−
*JO21095: Exposure to an [[Regimen_classes#Anthracycline-based_regimen|anthracycline-containing regimen]] and [[#Docetaxel_monotherapy_3|docetaxel]], with PD
 
−
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
 
−
====Biomarker eligibility criteria====
 
−
*DESTINY-Breast04: HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
 
−
*TROPiCS-02: HR+
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# Blum JL, Jones SE, Buzdar AU, Mucci LoRusso P, Kuter I, Vogel C, Osterwalder B, Burger HU, Stoner Brown C, Griffin T. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol. 1999 Feb;17(2):485-93. [https://doi.org/10.1200/JCO.1999.17.2.485 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10080589 PubMed]
 
−
# Reichardt P, Von Minckwitz G, Thuss-Patience PC, Jonat W, Kölbl H, Jänicke F, Kieback DG, Kuhn W, Schindler AE, Mohrmann S, Kaufmann M, Lück HJ. Multicenter phase II study of oral capecitabine (Xeloda) in patients with metastatic breast cancer relapsing after treatment with a taxane-containing therapy. Ann Oncol. 2003 Aug;14(8):1227-33. [https://doi.org/10.1093/annonc/mdg346 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12881384 PubMed]
 
−
# '''AVF2119g:''' Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005 Feb 1;23(4):792-9. [https://doi.org/10.1200/JCO.2005.05.098 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15681523 PubMed] NCT00109239
 
−
<!-- Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 3, 2007, Chicago, IL. -->
 
−
# '''CA163-046:''' Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Pivot XB, Klimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat LT, Roché HH. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210-7. [https://doi.org/10.1200/jco.2007.12.6557 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17968020 PubMed] NCT00080301
 
−
## '''Update:''' Hortobagyi GN, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Lerzo GL, Pivot XB, Hurtado de Mendoza F, Xu B, Vahdat LT, Peck RA, Mukhopadhyay P, Roché HH. Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes. Breast Cancer Res Treat. 2010 Jul;122(2):409-18. Epub 2010 May 8. [https://doi.org/10.1007/s10549-010-0901-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20454927 PubMed]
 
−
# '''SUN 1107:''' Barrios CH, Liu MC, Lee SC, Vanlemmens L, Ferrero JM, Tabei T, Pivot X, Iwata H, Aogi K, Lugo-Quintana R, Harbeck N, Brickman MJ, Zhang K, Kern KA, Martin M. Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer. Breast Cancer Res Treat. 2010 May;121(1):121-31. Epub 2010 Mar 26. [https://doi.org/10.1007/s10549-010-0788-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855860/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20339913 PubMed]
 
−
<!-- Presented in part at the American Society of Clinical Oncology Breast Cancer Symposium, September 5-7, 2008, Washington, DC (abstr 186). -->
 
−
# '''CA163-048:''' Sparano JA, Vrdoljak E, Rixe O, Xu B, Manikhas A, Medina C, Da Costa SC, Ro J, Rubio G, Rondinon M, Perez Manga G, Peck R, Poulart V, Conte P. Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2010 Jul 10;28(20):3256-63. [https://doi.org/10.1200/jco.2009.24.4244 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903325/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20530276 PubMed] NCT00082433
 
−
# '''HORG CT/02.11:''' Pallis AG, Boukovinas I, Ardavanis A, Varthalitis I, Malamos N, Georgoulias V, Mavroudis D; Hellenic Oncology Research Group. A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer. Ann Oncol. 2012 May;23(5):1164-9. Epub 2011 Sep 21. [https://doi.org/10.1093/annonc/mdr405 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21937705 PubMed] NCT00431106
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
<!-- Presented in part at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''A6181099:''' Crown JP, Diéras V, Staroslawska E, Yardley DA, Bachelot T, Davidson N, Wildiers H, Fasching PA, Capitain O, Ramos M, Greil R, Cognetti F, Fountzilas G, Blasinska-Morawiec M, Liedtke C, Kreienberg R, Miller WH Jr, Tassell V, Huang X, Paolini J, Kern KA, Romieu G. Phase III trial of sunitinib in combination with capecitabine versus capecitabine monotherapy for the treatment of patients with pretreated metastatic breast cancer. J Clin Oncol. 2013 Aug 10;31(23):2870-8. Epub 2013 Jul 15. [https://doi.org/10.1200/jco.2012.43.3391 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23857972 PubMed] NCT00435409
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
# '''E7389-G000-301:''' Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20;33(6):594-601. Epub 2015 Jan 20. [https://doi.org/10.1200/JCO.2013.52.4892 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463422/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25605862 PubMed] NCT00337103
 
−
# '''JO21095:''' Yamamoto D, Sato N, Rai Y, Yamamoto Y, Saito M, Iwata H, Masuda N, Oura S, Watanabe J, Hattori S, Matsuura Y, Kuroi K. Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. Breast Cancer Res Treat. 2017 Feb;161(3):473-482. Epub 2016 Dec 22. [https://doi.org/10.1007/s10549-016-4075-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28005247 PubMed]
 
−
# '''BG01-1323L:''' Zhang P, Sun T, Zhang Q, Yuan Z, Jiang Z, Wang XJ, Cui S, Teng Y, Hu XC, Yang J, Pan H, Tong Z, Li H, Yao Q, Wang Y, Yin Y, Sun P, Zheng H, Cheng J, Lu J, Zhang B, Geng C, Liu J, Peng R, Yan M, Zhang S, Huang J, Tang L, Qiu R, Xu B; BG01-1323L study group. Utidelone plus capecitabine versus capecitabine alone for heavily pretreated metastatic breast cancer refractory to anthracyclines and taxanes: a multicentre, open-label, superiority, phase 3, randomised controlled trial. Lancet Oncol. 2017 Mar;18(3):371-383. Epub 2017 Feb 11. [https://doi.org/10.1016/S1470-2045(17)30088-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28209298 PubMed] NCT02253459
 
−
## '''Update:''' Xu B, Sun T, Zhang Q, Zhang P, Yuan Z, Jiang Z, Wang X, Cui S, Teng Y, Hu XC, Yang J, Pan H, Tong Z, Li H, Yao Q, Wang Y, Yin Y, Sun P, Zheng H, Cheng J, Lu J, Zhang B, Geng C, Liu J, Shen K, Yu S, Li H, Tang L, Qiu R; study group of BG01-1323L. Efficacy of utidelone plus capecitabine versus capecitabine for heavily pretreated, anthracycline- and taxane-refractory metastatic breast cancer: final analysis of overall survival in a phase III randomised controlled trial. Ann Oncol. 2021 Feb;32(2):218-228. Epub 2020 Nov 11. [https://doi.org/10.1016/j.annonc.2020.10.600 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33188874/ PubMed]
 
−
# '''RESILIENCE:''' Baselga J, Zamagni C, Gómez P, Bermejo B, Nagai SE, Melichar B, Chan A, Mángel L, Bergh J, Costa F, Gómez HL, Gradishar WJ, Hudis CA, Rapoport BL, Roché H, Maeda P, Huang L, Meinhardt G, Zhang J, Schwartzberg LS. RESILIENCE: phase III randomized, double-blind trial comparing sorafenib with capecitabine versus placebo with capecitabine in locally advanced or metastatic HER2-negative breast cancer. Clin Breast Cancer. 2017 Dec;17(8):585-594.e4. Epub 2017 May 22. [https://www.clinical-breast-cancer.com/article/S1526-8209(17)30005-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28830796 PubMed] NCT01234337
 
−
# '''PROCEED:''' Park IH, Im SA, Jung KH, Sohn JH, Park YH, Lee KS, Sim SH, Park KH, Kim JH, Nam BH, Kim HJ, Kim TY, Lee KH, Kim SB, Ahn JH, Lee S, Ro J. Randomized open label phase III trial of irinotecan plus capecitabine versus capecitabine monotherapy in patients with metastatic breast cancer previously treated with anthracycline and taxane: PROCEED trial (KCSG BR 11-01). Cancer Res Treat. 2019 Jan;51(1):43-52. Epub 2018 Feb 14. [https://www.e-crt.org/journal/view.php?doi=10.4143/crt.2017.562 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333992/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29458237 PubMed] NCT01501669
 
−
# '''L00070 IN 305 B0:''' Martin M, Campone M, Bondarenko I, Sakaeva D, Krishnamurthy S, Roman L, Lebedeva L, Vedovato JC, Aapro M. Randomised phase III trial of vinflunine plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with an anthracycline and resistant to taxane. Ann Oncol. 2018 May 1;29(5):1195-1202. [https://doi.org/10.1093/annonc/mdy063 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29447329 PubMed] NCT01095003
 
−
# '''DESTINY-Breast04:''' Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. [https://doi.org/10.1056/nejmoa2203690 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35665782/ PubMed] NCT03734029
 
−
# '''EVER-132-002:''' NCT04639986
 
−
# '''TROPiCS-02:''' NCT03901339
 
−
 
 
−
==Capecitabine & Bevacizumab {{#subobject:16ed34|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, 2000/15 {{#subobject:a7ad32|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br> 2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br> 3. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br> 4. [[#Paclitaxel_monotherapy.2C_weekly_3|Paclitaxel]]<br> 5. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]<br> 6. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 7.2 vs 5.1 mo<br>(HR 0.78, 95% CI 0.64-0.93)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #2, 2500/15 {{#subobject:f3e77b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.05.098 Miller et al. 2005 (AVF2119g)]
 
−
|2000-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Capecitabine_monotherapy_3|Capecitabine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 4.86 vs 4.17 mo<br>(HR 0.98, 95% CI 0.77-1.25)
 
−
|-
 
−
|}
 
−
''Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.''
 
−
====Prior treatment criteria====
 
−
*Prior therapy with both an anthracycline and a taxane, and 1 to 2 prior chemotherapy regimens for metastatic disease
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# '''AVF2119g:''' Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005 Feb 1;23(4):792-9. [https://doi.org/10.1200/JCO.2005.05.098 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15681523 PubMed] NCT00109239
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
 
 
−
==Capecitabine & Docetaxel (TX) {{#subobject:a11c57|Regimen=1}}==
 
−
 
 
−
TX: '''<u>T</u>'''axotere (Docetaxel) & '''<u>X</u>'''eloda (Capecitabine)
 
−
<br>XT: '''<u>X</u>'''eloda (Capecitabine) & '''<u>T</u>'''axotere (Docetaxel)
 
−
<br>DC: '''<u>D</u>'''ocetaxel & '''<u>C</u>'''apecitabine
 
−
<br>CD: '''<u>C</u>'''apecitabine & '''<u>D</u>'''ocetaxel
 
−
===Regimen variant #1, 825/60 {{#subobject:5bcf6a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-016-4075-6 Yamamoto et al. 2016 (JO21095)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Docetaxel_monotherapy_3|Docetaxel]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 10.5 vs 9.8 mo<br>(HR 0.62, 95% CI 0.40-0.97)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #2, 1250/75 {{#subobject:6c7dba|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.09.002 O'Shaughnessy et al. 2002]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Docetaxel_monotherapy_3|Docetaxel]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 14.5 vs 11.5 mo<br>(HR 0.78, 95% CI 0.645-0.94)
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2007.15.8485 Chan et al. 2009 (B9E-US-S188)]
 
−
|2002-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Gemcitabine_99|GD]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for O'Shaughnessy et al. 2002 is based on the 2004 update.''
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# O'Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol. 2002 Jun 15;20(12):2812-23. [https://doi.org/10.1200/jco.2002.09.002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12065558 PubMed]
 
−
## '''Update:''' Miles D, Vukelja S, Moiseyenko V, Cervantes G, Mauriac L, Van Hazel G, Liu WY, Ayoub JP, O'Shaughnessy JA. Survival benefit with capecitabine/docetaxel versus docetaxel alone: analysis of therapy in a randomized phase III trial. Clin Breast Cancer. 2004 Oct;5(4):273-8. [https://www.clinical-breast-cancer.com/article/S1526-8209(11)70377-9/pdf link to original article] [https://pubmed.ncbi.nlm.nih.gov/15507172 PubMed]
 
−
# '''B9E-US-S188:''' Chan S, Romieu G, Huober J, Delozier T, Tubiana-Hulin M, Schneeweiss A, Lluch A, Llombart A, du Bois A, Kreienberg R, Mayordomo JI, Antón A, Harrison M, Jones A, Carrasco E, Vaury AT, Frimodt-Moller B, Fumoleau P. Phase III study of gemcitabine plus docetaxel compared with capecitabine plus docetaxel for anthracycline-pretreated patients with metastatic breast cancer. J Clin Oncol. 2009 Apr 10;27(11):1753-60. Epub 2009 Mar 9. [https://doi.org/10.1200/JCO.2007.15.8485 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19273714 PubMed] NCT00191152
 
−
## '''Pooled update:''' Seidman AD, Chan S, Wang J, Zhu C, Xu C, Xu B. A pooled analysis of gemcitabine plus docetaxel versus capecitabine plus docetaxel in metastatic breast cancer. Oncologist. 2014 May;19(5):443-52. Epub 2014 Apr 4. [https://doi.org/10.1634/theoncologist.2013-0428 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4012969/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24705980/ PubMed]
 
−
# '''JO21095:''' Yamamoto D, Sato N, Rai Y, Yamamoto Y, Saito M, Iwata H, Masuda N, Oura S, Watanabe J, Hattori S, Matsuura Y, Kuroi K. Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. Breast Cancer Res Treat. 2017 Feb;161(3):473-482. Epub 2016 Dec 22. [https://doi.org/10.1007/s10549-016-4075-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28005247 PubMed]
 
−
 
 
−
==Capecitabine & Ixabepilone {{#subobject:9ce286|Regimen=1}}==
 
−
 
 
−
XI: '''<u>X</u>'''eloda (Capecitabine) & '''<u>I</u>'''xabepilone
 
−
===Regimen {{#subobject:f5cae3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.12.6557 Thomas et al. 2007 (CA163-046)]
 
−
|2003-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Capecitabine_monotherapy_3|Capecitabine]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 5.8 vs 4.2 mo<br>(HR 0.75, 95% CI 0.64-0.88)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903325/ Sparano et al. 2010 (CA163-048)]
 
−
|2003-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Capecitabine_monotherapy_3|Capecitabine]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 16.4 vs 15.6 mo<br>(HR 0.90, 95% CI 0.78-1.03)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Ixabepilone (Ixempra)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
<!-- Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 3, 2007, Chicago, IL. -->
 
−
# '''CA163-046:''' Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Pivot XB, Klimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat LT, Roché HH. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210-7. [https://doi.org/10.1200/jco.2007.12.6557 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17968020 PubMed] NCT00080301
 
−
## '''Update:''' Hortobagyi GN, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Lerzo GL, Pivot XB, Hurtado de Mendoza F, Xu B, Vahdat LT, Peck RA, Mukhopadhyay P, Roché HH. Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes. Breast Cancer Res Treat. 2010 Jul;122(2):409-18. Epub 2010 May 8. [https://doi.org/10.1007/s10549-010-0901-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20454927 PubMed]
 
−
<!-- Presented in part at the American Society of Clinical Oncology Breast Cancer Symposium, September 5-7, 2008, Washington, DC (abstr 186). -->
 
−
# '''CA163-048:''' Sparano JA, Vrdoljak E, Rixe O, Xu B, Manikhas A, Medina C, Da Costa SC, Ro J, Rubio G, Rondinon M, Perez Manga G, Peck R, Poulart V, Conte P. Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2010 Jul 10;28(20):3256-63. [https://doi.org/10.1200/jco.2009.24.4244 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903325/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20530276 PubMed] NCT00082433
 
−
 
 
−
==Capecitabine & Vinflunine {{#subobject:bd9hg1|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:f3e92c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdy063 Martin et al. 2018 (L00070 IN 305 B0)]
 
−
|2009-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Capecitabine_monotherapy_3|Capecitabine]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 5.6 vs 4.3 mo<br>(HR 0.84, 95% CI 0.71-0.99)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Vinflunine (Javlor)]] 280 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
===References===
 
−
# '''L00070 IN 305 B0:''' Martin M, Campone M, Bondarenko I, Sakaeva D, Krishnamurthy S, Roman L, Lebedeva L, Vedovato JC, Aapro M. Randomised phase III trial of vinflunine plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with an anthracycline and resistant to taxane. Ann Oncol. 2018 May 1;29(5):1195-1202. [https://doi.org/10.1093/annonc/mdy063 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29447329 PubMed] NCT01095003
 
−
 
 
−
==Carboplatin & Gemcitabine (GCb) {{#subobject:83a5ee|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:e571d|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.clinical-breast-cancer.com/article/S1526-8209(11)70540-7 Nagourney et al. 2008]
 
−
|2002-2005
 
−
| style="background-color:#ffffbe" |Pilot, less than 20 pts
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Carboplatin (Paraplatin)]] AUC 2 IV over 60 minutes once per day on days 1 & 8
 
−
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8
 
−
 
 
−
'''21-day cycles until CR or indefinitely'''
 
−
 
 
−
===References===
 
−
# Nagourney RA, Flam M, Link J, Hager S, Blitzer J, Lyons W, Sommers BL, Evans S. Carboplatin plus gemcitabine repeating doublet therapy in recurrent breast cancer. Clin Breast Cancer. 2008 Oct;8(5):432-5. [http://www.clinical-breast-cancer.com/article/S1526-8209(11)70540-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18952557 PubMed]
 
−
 
 
−
==Cisplatin & Vinorelbine (CVb) {{#subobject:c1c866|Regimen=1}}==
 
−
 
 
−
CVb: '''<u>C</u>'''isplatin & '''<u>V</u>'''inorel'''<u>b</u>'''ine
 
−
===Regimen {{#subobject:9caba1|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1002/(SICI)1097-0142(19980101)82:1%3C134::AID-CNCR16%3E3.0.CO;2-3 Ray-Coquard et al. 1998]
 
−
|1992-1994
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://doi.org/10.1023/a:1008377724931 Vassilomanolakis et al. 2000]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV over 5 to 10 minutes once per day on days 1 & 8
 
−
 
 
−
====Supportive therapy====
 
−
*Normal saline 200 mL bolus after [[Vinorelbine (Navelbine)]] to prevent phlebitis
 
−
*Normal saline 2000 mL with KCl (unspecified amount of KCl) IV over 4 hours once on day 1, prior to [[Cisplatin (Platinol)]]
 
−
*[[Furosemide (Lasix)]] 40 mg IV once on day 1; 20 minutes prior to [[Cisplatin (Platinol)]]
 
−
*Normal saline 1000 mL and D5W 1000 mL IV over 4 hours once on day 1, after [[Cisplatin (Platinol)]]
 
−
**Paper did not say whether fluids were given sequentially or concurrently
 
−
*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonists]] used
 
−
 
 
−
'''21-day cycle for up to 6 cycles'''
 
−
 
 
−
===References===
 
−
# Ray-Coquard I, Biron P, Bachelot T, Guastalla JP, Catimel G, Merrouche Y, Droz JP, Chauvin F, Blay JY. Vinorelbine and cisplatin (CIVIC regimen) for the treatment of metastatic breast carcinoma after failure of anthracycline- and/or paclitaxel-containing regimens. Cancer. 1998 Jan 1;82(1):134-40. [https://doi.org/10.1002/(SICI)1097-0142(19980101)82:1%3C134::AID-CNCR16%3E3.0.CO;2-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9428489 PubMed]
 
−
# Vassilomanolakis M, Koumakis G, Barbounis V, Demiri M, Pateras H, Efremidis AP. Vinorelbine and cisplatin in metastatic breast cancer patients previously treated with anthracyclines. Ann Oncol. 2000 Sep;11(9):1155-60. [https://doi.org/10.1023/a:1008377724931 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11061611 Pubmed]
 
−
 
 
−
==Cyclophosphamide & Methotrexate (CM) {{#subobject:fb8chd|Regimen=1}}==
 
−
 
 
−
CM: '''<u>C</u>'''yclophosphamide & '''<u>M</u>'''ethotrexate
 
−
===Regimen variant #1 {{#subobject:fc3ubz|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdf013 Colleoni et al. 2002]
 
−
|1997-2000
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day
 
−
*[[Methotrexate (MTX)]] 2.5 mg PO twice per day on days 1 & 2
 
−
 
 
−
'''7-day cycles'''
 
−
 
 
−
===Regimen variant #2, metronomic {{#subobject:fcdhb1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdj066 Colleoni et al. 2005]
 
−
|2000-2003
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#Cyclophosphamide_.26_Methotrexate_.28CM.29_.26_Thalidomide_99|CM & Thalidomide]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of % reduction in VEGF after 2 months of treatment
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day
 
−
*[[Methotrexate (MTX)]] 2.5 mg PO twice per day on days 1 & 4
 
−
 
 
−
'''7-day cycles'''
 
−
 
 
−
===References===
 
−
# Colleoni M, Rocca A, Sandri MT, Zorzino L, Masci G, Nolè F, Peruzzotti G, Robertson C, Orlando L, Cinieri S, de Braud F, Viale G, Goldhirsch A. Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels. Ann Oncol. 2002 Jan;13(1):73-80. [https://doi.org/10.1093/annonc/mdf013 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11863115 PubMed]
 
−
# Colleoni M, Orlando L, Sanna G, Rocca A, Maisonneuve P, Peruzzotti G, Ghisini R, Sandri MT, Zorzino L, Nolè F, Viale G, Goldhirsch A. Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects. Ann Oncol. 2006 Feb;17(2):232-8. Epub 2005 Dec 1. [https://doi.org/10.1093/annonc/mdj066 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16322118 PubMed]
 
−
 
 
−
==Cyclophosphamide monotherapy {{#subobject:fb7cyd|Regimen=1}}==
 
−
 
 
−
===Regimen {{#subobject:fc71g9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdy051 Cortes et al. 2018 (L00070 IN 308 B0)]
 
−
|2009-2011 (C)
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Vinflunine_monotherapy_99|Vinflunine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 9.3 vs 9.1 mo<br>(HR 0.96)
 
−
|-
 
−
|}
 
−
''Note: this was the most commonly used comparator arm; doses were not provided in the manuscript.''
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
 
 
−
===References===
 
−
# '''L00070 IN 308 B0:''' Cortes J, Perez-Garcia J, Levy C, Gómez Pardo P, Bourgeois H, Spazzapan S, Martínez-Jañez N, Chao TC, Espié M, Nabholtz JM, Gonzàlez Farré X, Beliakouski V, Román García J, Holgado E, Campone M. Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer. Ann Oncol. 2018 Apr 1;29(4):881-887. [https://doi.org/10.1093/annonc/mdy051 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29481630 PubMed] NCT01091168
 
−
 
 
−
==Docetaxel monotherapy {{#subobject:fb8c8d|Regimen=1}}==
 
−
 
 
−
D: '''<u>D</u>'''ocetaxel
 
−
<br>T: '''<u>T</u>'''axotere (Docetaxel)
 
−
===Regimen variant #1, 40 mg/m<sup>2</sup> 3 weeks out of 4 {{#subobject:f1b265|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.23321 Rivera et al. 2008]
 
−
|2001-2004
 
−
| style="background-color:#91cf61" |Phase 3 (C), less than 20 pts in this subgroup
 
−
|[[#Docetaxel_monotherapy_3|Docetaxel]]; q3wk
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
| style="background-color:#1a9850" |Superior toxicity
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycle 1: 35 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 
−
**Cycle 2 onwards: 40 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===Regimen variant #2, 40 mg/m<sup>2</sup> 6 weeks out of 8 {{#subobject:b23d7b|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2000.18.6.1212 Burstein et al. 2000]
 
−
|1998
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
 
−
 
 
−
'''8-week cycles'''
 
−
 
 
−
===Regimen variant #3, 60 mg/m<sup>2</sup> {{#subobject:f90ee9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074308/ Adachi et al. 1996]
 
−
|1993
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2005.05.0294 Harvey et al. 2006 (TAX 313)]
 
−
| rowspan="2" |1995-2001
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-de-esc)
 
−
|1. [[#Docetaxel_monotherapy_3|Docetaxel]]; 75 mg/m<sup>2</sup> q3wk
 
−
| style="background-color:#fee08b" |Might have inferior TTP
 
−
|-
 
−
|2. [[#Docetaxel_monotherapy_3|Docetaxel]]; 100 mg/m<sup>2</sup> q3wk
 
−
| style="background-color:#fee08b" |Might have inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: this is the dosage used for Japanese patients; Adachi et al. 1996 reported 21- to 28-day cycles''
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #4, 70 mg/m<sup>2</sup> {{#subobject:a74e46|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-016-4075-6 Yamamoto et al. 2016 (JO21095)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_3|TX]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 70 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*Upon progression: [[#Capecitabine_monotherapy_2|Capecitabine]]
+
*[[Surgery#Surgical_resection|Complete resection]]
−
 
+
</div></div>
−
===Regimen variant #5, 75 mg/m<sup>2</sup> {{#subobject:81b82f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2005.05.0294 Harvey et al. 2006 (TAX 313)]
 
−
| rowspan="2" |1995-2001
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[#Docetaxel_monotherapy_3|Docetaxel]]; 60 mg/m<sup>2</sup> q3wk
 
−
| style="background-color:#d9ef8b" |Might have superior TTP
 
−
|-
 
−
|2. [[#Docetaxel_monotherapy_3|Docetaxel]]; 100 mg/m<sup>2</sup> q3wk
 
−
| style="background-color:#fee08b" |Might have inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br> 2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br> 3. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br> 4. [[#Paclitaxel_.26_Bevacizumab_2|Paclitaxel & Bevacizumab]]<br> 5. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]] <br> 6. [[#Vinorelbine_.26_Bevacizumab|Vinorelbine & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: This is the lower end of the range of docetaxel dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===Regimen variant #6, 100 mg/m<sup>2</sup> {{#subobject:67c50d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://www.annalsofoncology.org/article/S0923-7534(19)63147-9/pdf ten Bokkel Huinink et al. 1994]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1999.17.5.1413 Nabholtz et al. 1999 (TAX 304)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-de-esc)
 
−
|[[#Mitomycin_.26_Vinblastine_.28MV.29_88|Mitomycin & Vinblastine (MV)]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1999.17.8.2341 Chan et al. 1999 (TAX 303)]
 
−
|1994-1997
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Doxorubicin_monotherapy_3|Doxorubicin]]
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(99)00122-7 Sjöström et al. 1999]
 
−
|1994-1997
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#Fluorouracil_.26_Methotrexate_.28MF.29_88|MF]]
 
−
| style="background-color:#1a9850" |Superior TTP
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.09.002 O'Shaughnessy et al. 2002]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Docetaxel_.28TX.29_3|TX]]
 
−
| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.02.027 Jones et al. 2005 (TAX 311)]
 
−
|1994-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Paclitaxel_monotherapy.2C_q3wk_2|Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 15.4 vs 12.7 mo<br>(HR 0.71, 95% CI 0.58-0.87)
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408916/ Bonneterre et al. 2002]
 
−
|1995-1997
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#Fluorouracil_.26_Vinorelbine_88|5-FU & Vinorelbine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
| style="background-color:#1a9850" |Less toxic
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2005.05.0294 Harvey et al. 2006 (TAX 313)]
 
−
|rowspan=2|1995-2001
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[#Docetaxel_monotherapy_3|Docetaxel]]; 60 mg/m<sup>2</sup> q3wk
 
−
| style="background-color:#d9ef8b" |Might have superior TTP
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|2. [[#Docetaxel_monotherapy_3|Docetaxel]]; 75 mg/m<sup>2</sup> q3wk
 
−
| style="background-color:#d9ef8b" |Might have superior TTP
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.23321 Rivera et al. 2008]
 
−
|2001-2004
 
−
| style="background-color:#91cf61" |Phase 3 (C), less than 20 pts in this subgroup
 
−
|[[#Docetaxel_monotherapy_3|Docetaxel]]; weekly
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
| style="background-color:#d73027" |Inferior toxicity
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.33.9507 Nielsen et al. 2011]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Gemcitabine_88|Docetaxel & Gemcitabine]]
 
−
| style="background-color:#fee08b" |Might have inferior TTP
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(10)01207-4 Schröder et al. 2011]
 
−
|2001-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_monotherapy_3|Docetaxel]]; weekly
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br> 2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br> 3. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br> 4. [[#Paclitaxel_.26_Bevacizumab_2|Paclitaxel & Bevacizumab]]<br> 5. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]] <br> 6. [[#Vinorelbine_.26_Bevacizumab|Vinorelbine & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for O'Shaughnessy et al. 2002 is based on the 2004 update.''<br>
 
−
''Note: this is the upper end of the range of docetaxel dosing described in TANIA. TAX 304 stopped treatment after 10 cycles. TAX 303 stopped treatment after 7 cycles.''
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
**Note: Rivera et al. 2008 gave 75 mg/m<sup>2</sup> in cycle 1, with escalation to 100 mg/m<sup>2</sup> depending on toxicity
 
−
 
 
−
'''21-day cycles (see note)'''
 
−
 
 
 
===References===
 
===References===
−
# ten Bokkel Huinink WW, Prove AM, Piccart M, Steward W, Tursz T, Wanders J, Franklin H, Clavel M, Verweij J, Alakl M, Bayssas M, Kaye SB; [[Study_Groups#EORTC|EORTC]] Early Clinical Trials Group. A phase II trial with docetaxel (Taxotere) in second line treatment with chemotherapy for advanced breast cancer: a study of the EORTC Early Clinical Trials Group. Ann Oncol. 1994 Jul;5(6):527-32. [https://www.annalsofoncology.org/article/S0923-7534(19)63147-9/pdf link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7918124 PubMed]
+
#'''CheckMate 816:''' Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. [https://doi.org/10.1056/nejmoa2202170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35403841/ PubMed] [https://clinicaltrials.gov/study/NCT02998528 NCT02998528]
−
# Adachi I, Watanabe T, Takashima S, Narabayashi M, Horikoshi N, Aoyama H, Taguchi T. A late phase II study of RP56976 (docetaxel) in patients with advanced or recurrent breast cancer. Br J Cancer. 1996 Jan;73(2):210-6. [https://doi.org/10.1038/bjc.1996.37 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074308/ link to PMC article] '''contains dosing details in abstract'''  [https://pubmed.ncbi.nlm.nih.gov/8546908 PubMed]
+
Start of hidden/commented information for virtual editor End of hidden/commented information for virtual editor
−
# '''TAX 304:''' Nabholtz JM, Senn HJ, Bezwoda WR, Melnychuk D, Deschênes L, Douma J, Vandenberg TA, Rapoport B, Rosso R, Trillet-Lenoir V, Drbal J, Molino A, Nortier JW, Richel DJ, Nagykalnai T, Siedlecki P, Wilking N, Genot JY, Hupperets PS, Pannuti F, Skarlos D, Tomiak EM, Murawsky M, Alakl M, Aapro M; 304 Study Group. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. J Clin Oncol. 1999 May;17(5):1413-24. [https://doi.org/10.1200/JCO.1999.17.5.1413 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10334526 PubMed]
 
−
# '''Review:''' Burris HA 3rd. Single-agent docetaxel (Taxotere) in randomized phase III trials. Semin Oncol. 1999 Jun;26(3 Suppl 9):1-6. [https://pubmed.ncbi.nlm.nih.gov/10426452 PubMed]
 
−
# '''TAX 303:''' Chan S, Friedrichs K, Noel D, Pintér T, Van Belle S, Vorobiof D, Duarte R, Gil Gil M, Bodrogi I, Murray E, Yelle L, von Minckwitz G, Korec S, Simmonds P, Buzzi F, González Mancha R, Richardson G, Walpole E, Ronzoni M, Murawsky M, Alakl M, Riva A, Crown J; 303 Study Group. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2341-54. [https://doi.org/10.1200/jco.1999.17.8.2341 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561296 PubMed]
 
−
# Sjöström J, Blomqvist C, Mouridsen H, Pluzanska A, Ottosson-Lönn S, Bengtsson NO, Ostenstad B, Mjaaland I, Palm-Sjövall M, Wist E, Valvere V, Anderson H, Bergh J; Scandinavian Breast Group. Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group. Eur J Cancer. 1999 Aug;35(8):1194-201. [https://www.ejcancer.com/article/S0959-8049(99)00122-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10615229 PubMed]
 
−
# O'Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol. 2002 Jun 15;20(12):2812-23. [https://doi.org/10.1200/jco.2002.09.002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12065558 PubMed]
 
−
## '''Update:''' Miles D, Vukelja S, Moiseyenko V, Cervantes G, Mauriac L, Van Hazel G, Liu WY, Ayoub JP, O'Shaughnessy JA. Survival benefit with capecitabine/docetaxel versus docetaxel alone: analysis of therapy in a randomized phase III trial. Clin Breast Cancer. 2004 Oct;5(4):273-8. [https://www.clinical-breast-cancer.com/article/S1526-8209(11)70377-9/pdf link to original article] [https://pubmed.ncbi.nlm.nih.gov/15507172 PubMed]
 
−
# Bonneterre J, Roché H, Monnier A, Guastalla JP, Namer M, Fargeot P, Assadourian S. Docetaxel vs 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure. Br J Cancer. 2002 Nov 18;87(11):1210-5. [https://www.nature.com/articles/6600645 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408916/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/12439707 PubMed]
 
−
# '''TAX 311:''' Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, Laufman L, Sundaram S, Urba WJ, Pritchard KI, Mennel R, Richards D, Olsen S, Meyers ML, Ravdin PM. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol. 2005 Aug 20;23(24):5542-51. [https://doi.org/10.1200/JCO.2005.02.027 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16110015 PubMed] NCT00002662
 
−
# '''TAX 313:''' Harvey V, Mouridsen H, Semiglazov V, Jakobsen E, Voznyi E, Robinson BA, Groult V, Murawsky M, Cold S. Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol. 2006 Nov 1;24(31):4963-70. Epub 2006 Oct 10. [https://doi.org/10.1200/jco.2005.05.0294 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17033039 PubMed]
 
−
# Rivera E, Mejia JA, Arun BK, Adinin RB, Walters RS, Brewster A, Broglio KR, Yin G, Esmaeli B, Hortobagyi GN, Valero V. Phase 3 study comparing the use of docetaxel on an every-3-week versus weekly schedule in the treatment of metastatic breast cancer. Cancer. 2008 Apr 1;112(7):1455-61. [https://doi.org/full/10.1002/cncr.23321 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18300256 PubMed]
 
−
# Schröder CP, de Munck L, Westermann AM, Smit WM, Creemers GJ, de Graaf H, Stouthard JM, van Deijk G, Erjavec Z, van Bochove A, Vader W, Willemse PH. Weekly docetaxel in metastatic breast cancer patients: no superior benefits compared to three-weekly docetaxel. Eur J Cancer. 2011 Jun;47(9):1355-62. Epub 2011 Jan 19. [https://www.ejcancer.com/article/S0959-8049(10)01207-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21251813 PubMed]
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
# Nielsen DL, Bjerre KD, Jakobsen EH, Cold S, Stenbygaard L, Sørensen PG, Kamby C, Møller S, Jørgensen CL, Andersson M; Danish Breast Cancer Cooperative Group. Gemcitabine plus docetaxel versus docetaxel in patients with predominantly human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: a randomized, phase III study by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2011 Dec 20;29(36):4748-54. Epub 2011 Nov 14. [https://doi.org/10.1200/JCO.2010.33.9507 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22084374 PubMed]
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
# '''JO21095:''' Yamamoto D, Sato N, Rai Y, Yamamoto Y, Saito M, Iwata H, Masuda N, Oura S, Watanabe J, Hattori S, Matsuura Y, Kuroi K. Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. Breast Cancer Res Treat. 2017 Feb;161(3):473-482. Epub 2016 Dec 22. [https://doi.org/10.1007/s10549-016-4075-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28005247 PubMed]
 
−
# '''ATTAIN:''' Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. [https://doi.org/10.1001/jamaoncol.2022.0514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100460/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35552364/ PubMed] NCT02915744
 
−
 
 
−
==Docetaxel & Bevacizumab {{#subobject:481e73|Regimen=1}}==
 
−
 
 
−
===Regimen variant #1, docetaxel 60 mg/m<sup>2</sup> {{#subobject:f90ee9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
''Note: this is the dosage used for Japanese patients.''
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
  
−
'''21-day cycles'''
 
−
 
−
===Regimen variant #2, docetaxel 75 mg/m<sup>2</sup> {{#subobject:81b82f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br> 2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br> 3. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br> 4. [[#Paclitaxel_monotherapy.2C_weekly_3|Paclitaxel]]<br> 5. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]<br> 6. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 7.2 vs 5.1 mo<br>(HR 0.78, 95% CI 0.64-0.93)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
''Note: this is the lower end of the range of docetaxel dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===Regimen variant #3, docetaxel 100 mg/m<sup>2</sup> {{#subobject:67c50d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br> 2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br> 3. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br> 4. [[#Paclitaxel_monotherapy.2C_weekly_3|Paclitaxel]]<br> 5. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]<br> 6. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 7.2 vs 5.1 mo<br>(HR 0.78, 95% CI 0.64-0.93)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
''Note: this is the upper end of the range of docetaxel dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
 
−
==Docetaxel & Gemcitabine {{#subobject:80fe2|Regimen=1}}==
 
−
 
−
DG: '''<u>D</u>'''ocetaxel & '''<u>G</u>'''emcitabine
 
−
===Regimen {{#subobject:2d16cd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-009-0553-4 Tomova et al. 2010]
 
−
|NR in abstract
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Docetaxel_monotherapy_3|Docetaxel]], then [[#Gemcitabine_monotherapy_2|Gemcitabine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 8
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
−
'''21-day cycle for 8 cycles'''
 
−
 
−
===References===
 
−
# Tomova A, Bartsch R, Brodowicz T, Tzekova V, Timcheva C, Wiltschke C, Gerges DA, Pawlega J, Spanik S, Inbar M, Zielinski CC. Concomitant docetaxel plus gemcitabine versus sequential docetaxel followed by gemcitabine in anthracycline-pretreated metastatic or locally recurrent inoperable breast cancer patients: a prospective multicentre trial of the Central European Cooperative Oncology Group (CECOG). Breast Cancer Res Treat. 2010 Jan;119(1):169-76. [https://doi.org/10.1007/s10549-009-0553-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19768533/ PubMed]
 
−
 
−
==Doxorubicin monotherapy {{#subobject:4f9e89|Regimen=1}}==
 
−
 
−
===Regimen variant #1, 20 mg/m<sup>2</sup> weekly {{#subobject:39a14f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: this is the lower end of the range of weekly doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 20 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''7-day cycles'''
 
−
 
−
===Regimen variant #2, 25 mg/m<sup>2</sup> weekly {{#subobject:903e76|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: this is the higher end of the range of weekly doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''7-day cycles'''
 
−
 
−
===Regimen variant #3, 60 mg/m<sup>2</sup> q3wk {{#subobject:fdff75|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://academic.oup.com/jnci/article-abstract/83/15/1077/882648 Cowan et al. 1991 (SWOG S8203)]
 
−
|1983-1986
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Bisantrene_monotherapy_77|Bisantrene]]<br> 2. [[Breast_cancer_-_historical#Mitoxantrone_monotherapy|Mitoxantrone]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.12.2385 Norris et al. 2000 (NCIC-CTG MA.8)]
 
−
|1992-1995
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Vinorelbine_.28NA.29_99|NA]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2003.04.075 Reyno et al. 2004 (NCIC CT MA.19)]
 
−
|1998-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Tesmilifene_77|Doxorubicin & Tesmilifene]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: in NCIC-CTG MA.8, this dose was after a mid-protocol amendment. Treatment in NCIC-CTG MA.8 & MA.19 was given until a cumulative dose of 450 mg/m<sup>2</sup>. This is the lower end of the range of q3wk doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''21-day cycles (see note)'''
 
−
 
−
===Regimen variant #4, 75 mg/m<sup>2</sup> q3wk, limited duration {{#subobject:ccbd9e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1999.17.8.2341 Chan et al. 1999 (TAX 303)]
 
−
|1994-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_monotherapy_3|Docetaxel]]
 
−
| style="background-color:#d73027" |Inferior ORR
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''21-day cycle for up to 7 cycles'''
 
−
 
−
===Regimen variant #5, 75 mg/m<sup>2</sup> q3wk, indefinite {{#subobject:a3529b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150384/ Bontenbal et al. 1998 (EORTC 10811)]
 
−
|1982-1986
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_monotherapy_99|Epirubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: this is the higher end of the range of q3wk doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# '''SWOG S8203:''' Cowan JD, Neidhart J, McClure S, Coltman CA Jr, Gumbart C, Martino S, Hutchins LF, Stephens RL, Vaughan CB, Osborne CK. Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study. J Natl Cancer Inst. 1991 Aug 7;83(15):1077-84. [https://academic.oup.com/jnci/article-abstract/83/15/1077/882648 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1875415 PubMed]
 
−
# '''EORTC 10811:''' Bontenbal M, Andersson M, Wildiers J, Cocconi G, Jassem J, Paridaens R, Rotmensz N, Sylvester R, Mouridsen HT, Klijn JG, van Oosterom AT; [[Study_Groups#EORTC|EORTC]] Breast Cancer Cooperative Group. Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study in advanced breast cancer. Br J Cancer. 1998 Jun;77(12):2257-63. [https://www.nature.com/articles/bjc1998375 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150384/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9649142 PubMed]
 
−
# '''TAX 303:''' Chan S, Friedrichs K, Noel D, Pintér T, Van Belle S, Vorobiof D, Duarte R, Gil Gil M, Bodrogi I, Murray E, Yelle L, von Minckwitz G, Korec S, Simmonds P, Buzzi F, González Mancha R, Richardson G, Walpole E, Ronzoni M, Murawsky M, Alakl M, Riva A, Crown J; 303 Study Group. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2341-54. [https://doi.org/10.1200/jco.1999.17.8.2341 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561296 PubMed]
 
−
# '''NCIC-CTG MA.8:''' Norris B, Pritchard KI, James K, Myles J, Bennett K, Marlin S, Skillings J, Findlay B, Vandenberg T, Goss P, Latreille J, Rudinskas L, Lofters W, Trudeau M, Osoba D, Rodgers A. Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group study MA8. J Clin Oncol. 2000 Jun;18(12):2385-94. [https://doi.org/10.1200/JCO.2000.18.12.2385 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10856098 PubMed]
 
−
# '''NCIC CT MA.19:''' Reyno L, Seymour L, Tu D, Dent S, Gelmon K, Walley B, Pluzanska A, Gorbunova V, Garin A, Jassem J, Pienkowski T, Dancey J, Pearce L, MacNeil M, Marlin S, Lebwohl D, Voi M, Pritchard K; National Cancer Institute of Canada Clinical Trials Group. Phase III study of N,N-diethyl-2-[4-(phenylmethyl) phenoxy]ethanamine (BMS-217380-01) combined with doxorubicin versus doxorubicin alone in metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA.19. J Clin Oncol. 2004 Jan 15;22(2):269-76. [https://doi.org/10.1200/JCO.2003.04.075 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14722035 PubMed]
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
 
−
==Doxorubicin & Bevacizumab {{#subobject:b345a5|Regimen=1}}==
 
−
 
−
===Regimen variant #1, doxorubicin 20 mg/m<sup>2</sup> weekly {{#subobject:d9cf13|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
''Note: this is the lower end of the range of weekly doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #2, doxorubicin 25 mg/m<sup>2</sup> weekly {{#subobject:bb2f9f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
''Note: this is the higher end of the range of weekly doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #3, doxorubicin 60 mg/m<sup>2</sup> q3wk {{#subobject:e69410|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
''Note: this is the lower end of the range of q3wk doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===Regimen variant #4, doxorubicin 75 mg/m<sup>2</sup> q3wk {{#subobject:1effcd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
''Note: this is the higher end of the range of q3wk doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
 
−
==Eribulin monotherapy {{#subobject:ef2415|Regimen=1}}==
 
−
===Regimen variant #1 {{#subobject:25ef0y|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|Awaiting publication (TROPiCS-02)
 
−
|2019-2024
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Sacituzumab_govitecan_monotherapy_66|Sacituzumab govitecan]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
| style="background-color:#d73027" |Faster deterioration of global QoL
 
−
|-
 
−
|}
 
−
''Note: This dosing is the one commonly used in Europe. To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
====Biomarker eligibility criteria====
 
−
*TROPiCS-02: HR+
 
−
 
−
====Chemotherapy====
 
−
*[[Eribulin (Halaven)]] 1.23 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
−
'''21-day cycles'''
 
−
===Regimen variant #2 {{#subobject:25ef0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(11)60070-6 Cortes et al. 2011 (EMBRACE)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|Investigator's choice
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 13.1 vs 10.6 mo<br>(HR 0.81, 95% CI 0.66-0.99)
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463422/ Kaufman et al. 2015 (E7389-G000-301)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Capecitabine_monotherapy_3|Capecitabine]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 15.9 vs 14.5 mo<br>(HR 0.88, 95% CI 0.77-1.00)
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(15)00332-0 Perez et al. 2015 (BEACON<sub>brca</sub>)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Etirinotecan_pegol_monotherapy_77|Etirinotecan pegol]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/j.ejca.2019.02.002 Yuan et al. 2019 (E7389-C086-304)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Vinorelbine_monotherapy_2|Vinorelbine]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 2.8 vs 2.8 mo<br>(HR 0.80, 95% CI 0.65-0.98)
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100460/ Tripathy et al. 2022 (ATTAIN)]
 
−
|2017-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Etirinotecan_pegol_monotherapy_99|Etirinotecan pegol]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2203690 Modi et al. 2022 (DESTINY-Breast04)]
 
−
|2018-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|
 
−
|-
 
−
|Awaiting publication (TROPiCS-02)
 
−
|2019-2024
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Sacituzumab_govitecan_monotherapy_66|Sacituzumab govitecan]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
| style="background-color:#d73027" |Faster deterioration of global QoL
 
−
|-
 
−
|}
 
−
''Note: BEACON should not be confused for the trial by the same name in several other cancer types. This dosing is the one commonly used in North America.''
 
−
====Prior treatment criteria====
 
−
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
 
−
====Biomarker eligibility criteria====
 
−
*DESTINY-Breast04: HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
 
−
*TROPiCS-02: HR+
 
−
 
−
====Chemotherapy====
 
−
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV over 2 to 5 minutes once per day on days 1 & 8
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# '''EMBRACE:''' Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Diéras V, Delozier T, Vladimirov V, Cardoso F, Koh H, Bougnoux P, Dutcus CE, Seegobin S, Mir D, Meneses N, Wanders J, Twelves C; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011 Mar 12;377(9769):914-23. Epub 2011 Mar 2. [https://doi.org/10.1016/s0140-6736(11)60070-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21376385 PubMed] NCT00388726
 
−
# '''E7389-G000-301:''' Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20;33(6):594-601. Epub 2015 Jan 20. [https://doi.org/10.1200/JCO.2013.52.4892 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463422/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25605862 PubMed] NCT00337103
 
−
# '''BEACON<sub>brca</sub>:''' Perez EA, Awada A, O'Shaughnessy J, Rugo HS, Twelves C, Im SA, Gómez-Pardo P, Schwartzberg LS, Diéras V, Yardley DA, Potter DA, Mailliez A, Moreno-Aspitia A, Ahn JS, Zhao C, Hoch U, Tagliaferri M, Hannah AL, Cortes J. Etirinotecan pegol (NKTR-102) versus treatment of physician's choice in women with advanced breast cancer previously treated with an anthracycline, a taxane, and capecitabine (BEACON): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1556-1568. Epub 2015 Oct 22. [https://doi.org/10.1016/s1470-2045(15)00332-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26482278/ PubMed] NCT01492101
 
−
# '''E7389-C086-304:''' Yuan P, Hu X, Sun T, Li W, Zhang Q, Cui S, Cheng Y, Ouyang Q, Wang X, Chen Z, Hiraiwa M, Saito K, Funasaka S, Xu B. Eribulin mesilate versus vinorelbine in women with locally recurrent or metastatic breast cancer: A randomised clinical trial. Eur J Cancer. 2019 May;112:57-65. Epub 2019 Mar 29. [https://doi.org/10.1016/j.ejca.2019.02.002 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30928806/ PubMed] NCT02225470
 
−
# '''ATTAIN:''' Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. [https://doi.org/10.1001/jamaoncol.2022.0514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100460/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35552364/ PubMed] NCT02915744
 
−
# '''DESTINY-Breast04:''' Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. [https://doi.org/10.1056/nejmoa2203690 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35665782/ PubMed] NCT03734029
 
−
# '''EVER-132-002:''' NCT04639986
 
−
# '''TROPiCS-02:''' NCT03901339
 
−
 
−
==Gemcitabine monotherapy {{#subobject:af0915|Regimen=1}}==
 
−
 
−
===Regimen variant #1, 800 mg/m<sup>2</sup> 3 weeks out of 4 {{#subobject:4db8d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1995.13.11.2731 Carmichael et al. 1995]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2203690 Modi et al. 2022 (DESTINY-Breast04)]
 
−
|2018-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|
 
−
|-
 
−
|Awaiting publication (TROPiCS-02)
 
−
|2019-2024
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Sacituzumab_govitecan_monotherapy_66|Sacituzumab govitecan]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
| style="background-color:#d73027" |Faster deterioration of global QoL
 
−
|-
 
−
|}
 
−
''Note: this was the lower bound of dosing in DESTINY-Breast04 & TROPiCS-02.''
 
−
====Prior treatment criteria====
 
−
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
 
−
====Biomarker eligibility criteria====
 
−
*DESTINY-Breast04: HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
 
−
*TROPiCS-02: HR+
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #2, 1000 mg/m<sup>2</sup> 3 weeks out of 4 {{#subobject:b0f55d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #3, 1200 mg/m<sup>2</sup> 3 weeks out of 4 {{#subobject:3bbee6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[http://www.karger.com/Article/Abstract/58524 Spielmann et al. 2001]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2203690 Modi et al. 2022 (DESTINY-Breast04)]
 
−
|2018-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|
 
−
|-
 
−
|Awaiting publication (TROPiCS-02)
 
−
|2019-2024
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Sacituzumab_govitecan_monotherapy_66|Sacituzumab govitecan]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
| style="background-color:#d73027" |Faster deterioration of global QoL
 
−
|-
 
−
|}
 
−
''Note: this was the upper bound of dosing in DESTINY-Breast04 & TROPiCS-02.''
 
−
====Prior treatment criteria====
 
−
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
 
−
====Biomarker eligibility criteria====
 
−
*DESTINY-Breast04: HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
 
−
*TROPiCS-02: HR+
 
−
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1200 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #4, 1250 mg/m<sup>2</sup> 2 weeks out of 3 {{#subobject:11b425|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br> 2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br> 3. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br> 4. [[#Paclitaxel_.26_Bevacizumab_2|Paclitaxel & Bevacizumab]]<br> 5. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]] <br> 6. [[#Vinorelbine_.26_Bevacizumab|Vinorelbine & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# Carmichael J, Possinger K, Phillip P, Beykirch M, Kerr H, Walling J, Harris AL. Advanced breast cancer: a phase II trial with gemcitabine. J Clin Oncol. 1995 Nov;13(11):2731-6. [https://doi.org/10.1200/jco.1995.13.11.2731 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7595731 PubMed]
 
−
# Spielmann M, Llombart-Cussac A, Kalla S, Espié M, Namer M, Ferrero JM, Diéras V, Fumoleau P, Cuvier C, Perrocheau G, Ponzio A, Kayitalire L, Pouillart P. Single-agent gemcitabine is active in previously treated metastatic breast cancer. Oncology. 2001;60(4):303-7. [http://www.karger.com/Article/Abstract/58524 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11408796 PubMed]
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
# '''ATTAIN:''' Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. [https://doi.org/10.1001/jamaoncol.2022.0514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100460/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35552364/ PubMed] NCT02915744
 
−
# '''DESTINY-Breast04:''' Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. [https://doi.org/10.1056/nejmoa2203690 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35665782/ PubMed] NCT03734029
 
−
# '''EVER-132-002:''' NCT04639986
 
−
# '''TROPiCS-02:''' NCT03901339
 
−
 
−
==Gemcitabine & Bevacizumab {{#subobject:134dbe|Regimen=1}}==
 
−
 
−
===Regimen variant #1, 1000 mg/m<sup>2</sup>, 3 weeks out of 4 {{#subobject:ccfb9a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #2, 1250 mg/m<sup>2</sup>, 2 weeks out of 3 {{#subobject:15445c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br> 2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br> 3. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br> 4. [[#Paclitaxel_monotherapy.2C_weekly_3|Paclitaxel]]<br> 5. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]<br> 6. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 7.2 vs 5.1 mo<br>(HR 0.78, 95% CI 0.64-0.93)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
===References===
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
 
−
==Ixabepilone monotherapy {{#subobject:9df286|Regimen=1}}==
 
−
 
−
===Regimen {{#subobject:f4ab33|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2006.09.3849 Perez et al. 2007]
 
−
|2004-2005
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Ixabepilone (Ixempra)]] 40 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, Viens P, Cai C, Mullaney B, Peck R, Hortobagyi GN. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007 Aug 10;25(23):3407-14. Epub 2007 Jul 2. [https://doi.org/10.1200/JCO.2006.09.3849 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17606974 PubMed]
 
−
# '''ATTAIN:''' Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. [https://doi.org/10.1001/jamaoncol.2022.0514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100460/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35552364/ PubMed] NCT02915744
 
−
 
−
==Non-pegylated liposomal doxorubicin monotherapy {{#subobject:06760b|Regimen=1}}==
 
−
 
−
NPLD: '''<u>N</u>'''on-'''<u>P</u>'''egylated '''<u>L</u>'''iposomal '''<u>D</u>'''oxorubicin
 
−
===Regimen {{#subobject:2ed37f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Non-pegylated liposomal doxorubicin (Myocet)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
 
−
==Non-pegylated liposomal doxorubicin & Bevacizumab {{#subobject:2e10a5|Regimen=1}}==
 
−
 
−
NPLD & Bev: '''<u>N</u>'''on-'''<u>P</u>'''egylated '''<u>L</u>'''iposomal '''<u>D</u>'''oxorubicin & '''<u>Bev</u>'''acizumab
 
−
===Regimen {{#subobject:88281d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Non-pegylated liposomal doxorubicin (Myocet)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
 
−
==Paclitaxel monotherapy, weekly {{#subobject:b55e07|Regimen=1}}==
 
−
 
−
===Regimen variant #1, 80 mg/m<sup>2</sup> weekly {{#subobject:686fc8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2001.19.22.4216 Perez et al. 2001]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.11.6699 Seidman et al. 2008 (CALGB 9840)]
 
−
|1998-NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Paclitaxel_monotherapy.2C_q3wk_2|Paclitaxel]]; q3wk
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 24 vs 12 mo<br>(HR 0.78, 95% CI 0.65-0.94)
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2203690 Modi et al. 2022 (DESTINY-Breast04)]
 
−
|2018-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
====Prior treatment criteria====
 
−
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
 
−
====Biomarker eligibility criteria====
 
−
*DESTINY-Breast04: HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
 
−
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #2, 90 mg/m<sup>2</sup> 3 weeks out of 4 {{#subobject:55b062|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br> 2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br> 3. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br> 4. [[#Paclitaxel_.26_Bevacizumab_2|Paclitaxel & Bevacizumab]]<br> 5. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]] <br> 6. [[#Vinorelbine_.26_Bevacizumab|Vinorelbine & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 90 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===References===
 
−
# Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001 Nov 15;19(22):4216-23. [https://doi.org/10.1200/jco.2001.19.22.4216 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11709565 PubMed]
 
−
<!-- Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA. -->
 
−
# '''CALGB 9840:''' Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. [https://doi.org/10.1200/jco.2007.11.6699 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18375893 PubMed] NCT00003440
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
# '''ATTAIN:''' Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. [https://doi.org/10.1001/jamaoncol.2022.0514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100460/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35552364/ PubMed] NCT02915744
 
−
# '''DESTINY-Breast04:''' Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. [https://doi.org/10.1056/nejmoa2203690 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35665782/ PubMed] NCT03734029
 
−
 
−
==Paclitaxel monotherapy, q3wk {{#subobject:b90e58|Regimen=1}}==
 
−
 
−
===Regimen variant #1, 135 mg/m<sup>2</sup> {{#subobject:430acf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.6.1858 Nabholtz et al. 1996]
 
−
|1992
 
−
|style="background-color:#1a9851" |Phase 3 (E-RT-de-esc)
 
−
|[[#Paclitaxel_monotherapy.2C_q3wk_2|Paclitaxel]]; 175 mg/m<sup>2</sup> q3wk
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Although Nabholtz et al. 1996 did not meet its primary endpoint, there seemed to be a TTP disadvantage in the lower-dose arm.''
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===Regimen variant #2, 175 mg/m<sup>2</sup> {{#subobject:f2e948|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1995.13.10.2575 Seidman et al. 1995]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.6.1858 Nabholtz et al. 1996]
 
−
|1992
 
−
|style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Paclitaxel_monotherapy.2C_q3wk_2|Paclitaxel]]; 135 mg/m<sup>2</sup> q3wk
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.08.048 Winer et al. 2004 (CALGB 9342)]
 
−
|1994-1997
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Paclitaxel_monotherapy.2C_q3wk_2|Paclitaxel]]; 210 mg/m<sup>2</sup> q3wk<br> 2. [[#Paclitaxel_monotherapy.2C_q3wk_2|Paclitaxel]]; 250 mg/m<sup>2</sup> q3wk
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.02.027 Jones et al. 2005 (TAX 311)]
 
−
|1994-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Docetaxel_monotherapy_3|Docetaxel]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361864/ Icli et al. 2005]
 
−
|1997-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#EoP_88|EoP]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.11.6699 Seidman et al. 2008 (CALGB 9840)]
 
−
|1998-NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_monotherapy.2C_weekly_3|Paclitaxel]]; weekly
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.04.937 Gradishar et al. 2005 (CA012-0)]
 
−
|2001-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#d73027" |Inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br> 2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br> 3. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br> 4. [[#Paclitaxel_.26_Bevacizumab_2|Paclitaxel & Bevacizumab]]<br> 5. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]] <br> 6. [[#Vinorelbine_.26_Bevacizumab|Vinorelbine & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2203690 Modi et al. 2022 (DESTINY-Breast04)]
 
−
|2018-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Although Nabholtz et al. 1996 did not meet its primary endpoint, there seemed to be a TTP advantage in the higher-dose arm, which subsequently led to its adoption as the standard-of-care.''
 
−
====Prior treatment criteria====
 
−
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
 
−
====Biomarker eligibility criteria====
 
−
*DESTINY-Breast04: HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# Seidman AD, Tiersten A, Hudis C, Gollub M, Barrett S, Yao TJ, Lepore J, Gilewski T, Currie V, Crown J, Hakes T, Baselga J, Sklarin N, Moynihan ME, Tong W, Egorin M, Kearns C, Spriggs D, Norton L. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol. 1995 Oct;13(10):2575-81. [https://doi.org/10.1200/jco.1995.13.10.2575 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7595709 PubMed]
 
−
# Nabholtz JM, Gelmon K, Bontenbal M, Spielmann M, Catimel G, Conte P, Klaassen U, Namer M, Bonneterre J, Fumoleau P, Winograd B. Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol. 1996 Jun;14(6):1858-67. [https://doi.org/10.1200/JCO.1996.14.6.1858 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8656254 PubMed]
 
−
# '''CALGB 9342:''' Winer EP, Berry DA, Woolf S, Duggan D, Kornblith A, Harris LN, Michaelson RA, Kirshner JA, Fleming GF, Perry MC, Graham ML, Sharp SA, Keresztes R, Henderson IC, Hudis C, Muss H, Norton L. Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: Cancer and Leukemia Group B trial 9342. J Clin Oncol. 2004 Jun 1;22(11):2061-8. [https://doi.org/10.1200/JCO.2004.08.048 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15169793 PubMed]
 
−
# Icli F, Akbulut H, Uner A, Yalcin B, Baltali E, Altinbas M, Coşkun S, Komurcu S, Erkisi M, Demirkazik A, Senler FC, Sencan O, Büyükcelik A, Boruban C, Onur H, Zengin N, Sak SD; Turkish Oncology Group. Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group. Br J Cancer. 2005 Feb 28;92(4):639-44. [https://www.nature.com/articles/6602388 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361864/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15726120 PubMed]
 
−
# '''TAX 311:''' Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, Laufman L, Sundaram S, Urba WJ, Pritchard KI, Mennel R, Richards D, Olsen S, Meyers ML, Ravdin PM. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol. 2005 Aug 20;23(24):5542-51. [https://doi.org/10.1200/JCO.2005.02.027 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16110015 PubMed] NCT00002662
 
−
<!-- Presented in part at the 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003. -->
 
−
# '''CA012-0:''' Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. Epub 2005 Sep 19. [https://doi.org/10.1200/jco.2005.04.937 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16172456 PubMed] NCT00046527
 
−
<!-- Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA. -->
 
−
# '''CALGB 9840:''' Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. [https://doi.org/10.1200/jco.2007.11.6699 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18375893 PubMed] NCT00003440
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
# '''DESTINY-Breast04:''' Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. [https://doi.org/10.1056/nejmoa2203690 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35665782/ PubMed] NCT03734029
 
−
 
−
==Paclitaxel & Bevacizumab {{#subobject:1d634b|Regimen=1}}==
 
−
 
−
===Regimen variant #1, 90 mg/m<sup>2</sup> 3 weeks out of 4 {{#subobject:ba68f9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br> 2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br> 3. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br> 4. [[#Paclitaxel_monotherapy.2C_weekly_3|Paclitaxel]]; weekly<br> 5. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]<br> 6. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 7.2 vs 5.1 mo<br>(HR 0.78, 95% CI 0.64-0.93)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 90 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #2, 175 mg/m<sup>2</sup> q3wk {{#subobject:8820d1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br> 2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br> 3. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br> 4. [[#Paclitaxel_monotherapy.2C_weekly_3|Paclitaxel]]; weekly<br> 5. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]<br> 6. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 7.2 vs 5.1 mo<br>(HR 0.78, 95% CI 0.64-0.93)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
 
−
==nab-Paclitaxel monotherapy {{#subobject:7592da|Regimen=1}}==
 
−
 
−
===Example orders===
 
−
*[[Example orders for Paclitaxel, nanoparticle albumin-bound (Abraxane) in breast cancer]]
 
−
 
−
===Regimen variant #1, 100 mg/m<sup>2</sup>, 3 weeks out of 4 {{#subobject:4d1f30|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2203690 Modi et al. 2022 (DESTINY-Breast04)]
 
−
|2018-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
''Note: the details of this regimen are unclear in von Minckwitz et al. 2014.''
 
−
====Prior treatment criteria====
 
−
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
 
−
====Biomarker eligibility criteria====
 
−
*DESTINY-Breast04: HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #2, 125 mg/m<sup>2</sup>, 3 weeks out of 4 {{#subobject:4dhha0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2203690 Modi et al. 2022 (DESTINY-Breast04)]
 
−
|2018-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
====Prior treatment criteria====
 
−
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
 
−
====Biomarker eligibility criteria====
 
−
*DESTINY-Breast04: HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 125 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #3, 260 mg/m<sup>2</sup> q3wk {{#subobject:7d9620|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.04.937 Gradishar et al. 2005 (CA012-0)]
 
−
|2001-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Paclitaxel_monotherapy.2C_q3wk_2|Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior TTP<br>Median TTP: 23 vs 16.9 weeks<br>(HR 0.75)
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br> 2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br> 3. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br> 4. [[#Paclitaxel_.26_Bevacizumab_2|Paclitaxel & Bevacizumab]]<br> 5. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]] <br> 6. [[#Vinorelbine_.26_Bevacizumab|Vinorelbine & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2203690 Modi et al. 2022 (DESTINY-Breast04)]
 
−
|2018-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
====Prior treatment criteria====
 
−
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
 
−
====Biomarker eligibility criteria====
 
−
*DESTINY-Breast04: HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 260 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
−
 
−
====Supportive therapy====
 
−
*CA012-0: No corticosteroid or antihistamine premedication
 
−
 
−
'''21-day cycles'''
 
−
 
−
===Regimen variant #4, 300 mg/m<sup>2</sup> q3wk {{#subobject:7d7ym0|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.11.013 Ibrahim et al. 2005]
 
−
|1999-2001
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 300 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# Ibrahim NK, Samuels B, Page R, Doval D, Patel KM, Rao SC, Nair MK, Bhar P, Desai N, Hortobagyi GN. Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. J Clin Oncol. 2005 Sep 1;23(25):6019-26. [https://doi.org/10.1200/JCO.2005.11.013 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16135470 PubMed]
 
−
<!-- Presented in part at the 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003. -->
 
−
# '''CA012-0:''' Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. Epub 2005 Sep 19. [https://doi.org/10.1200/jco.2005.04.937 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16172456 PubMed] NCT00046527
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
# '''ATTAIN:''' Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. [https://doi.org/10.1001/jamaoncol.2022.0514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100460/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35552364/ PubMed] NCT02915744
 
−
# '''DESTINY-Breast04:''' Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. [https://doi.org/10.1056/nejmoa2203690 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35665782/ PubMed] NCT03734029
 
−
 
−
==Paclitaxel, nanoparticle albumin-bound & Bevacizumab {{#subobject:645e02|Regimen=1}}==
 
−
 
−
===Example orders===
 
−
*[[Example orders for Paclitaxel, nanoparticle albumin-bound & Bevacizumab in breast cancer]]
 
−
 
−
===Regimen variant #1, 100 mg/m<sup>2</sup> weekly {{#subobject:63e270|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
''Note: the schedule of bevacizumab is inferred, as there was insufficient detail in the description in the manuscript.''
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #2, 260 mg/m<sup>2</sup> q3wk {{#subobject:b2c00e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br> 2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br> 3. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br> 4. [[#Paclitaxel_monotherapy.2C_weekly_3|Paclitaxel]]; weekly<br> 5. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]<br> 6. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 7.2 vs 5.1 mo<br>(HR 0.78, 95% CI 0.64-0.93)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 260 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
 
−
==Pegylated liposomal doxorubicin monotherapy {{#subobject:06760b|Regimen=1}}==
 
−
 
−
PLD: '''<u>P</u>'''egylated '''<u>L</u>'''iposomal '''<u>D</u>'''oxorubicin
 
−
===Regimen variant #1, 40 mg/m<sup>2</sup> {{#subobject:2ed37f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: this is the lower end of the range of pegylated liposomal doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #2, 50 mg/m<sup>2</sup> {{#subobject:f033fb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.08.157 Keller et al. 2004]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Mitomycine_.26_Vinblastine_88|Mitomycin & Vinblastine]]<br> 2. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br>2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br>3. [[#Doxorubicin_.26_Bevacizumab|Doxorubicin & Bevacizumab]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_.26_Bevacizumab|NPLD & Bevacizumab]]<br>5. [[#Pegylated_liposomal_doxorubicin_.26_Bevacizumab|PLD & Bevacizumab]]<br>6. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br>7. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''Note: this is the higher end of the range of pegylated liposomal doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycles'''
 
−
 
−
===References===
 
−
# Keller AM, Mennel RG, Georgoulias VA, Nabholtz JM, Erazo A, Lluch A, Vogel CL, Kaufmann M, von Minckwitz G, Henderson IC, Mellars L, Alland L, Tendler C. Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. J Clin Oncol. 2004 Oct 1;22(19):3893-901. [https://doi.org/10.1200/JCO.2004.08.157 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15459210 PubMed]
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
 
−
==Pegylated liposomal doxorubicin & Bevacizumab {{#subobject:2e10a5|Regimen=1}}==
 
−
 
−
PLD & Bev: '''<u>P</u>'''egylated '''<u>L</u>'''iposomal '''<u>D</u>'''oxorubicin & '''<u>Bev</u>'''acizumab
 
−
===Regimen variant #1, 40 mg/m<sup>2</sup> {{#subobject:88281d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
''Note: this is the lower end of the range of pegylated liposomal doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===Regimen variant #2, 50 mg/m<sup>2</sup> {{#subobject:9feb98|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70439-5 von Minckwitz et al. 2014 (TANIA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br>3. [[#Doxorubicin_monotherapy_3|Doxorubicin]]<br>4. [[#Non-pegylated_liposomal_doxorubicin_monotherapy|NPLD]]<br>5. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]<br>6. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>7. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
−
|-
 
−
|}
 
−
''Note: this is the higher end of the range of pegylated liposomal doxorubicin dosing described in TANIA.''
 
−
====Chemotherapy====
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
===References===
 
−
# '''TANIA:''' von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. [https://doi.org/10.1016/S1470-2045(14)70439-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25273342 PubMed] NCT01250379
 
−
## '''Update:''' Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. [https://doi.org/10.1093/annonc/mdw316 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27502725 PubMed]
 
−
 
−
==Trastuzumab deruxtecan monotherapy {{#subobject:afhy8w|Regimen=1}}==
 
−
 
−
===Regimen {{#subobject:4cczw1d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2203690 Modi et al. 2022 (DESTINY-Breast04)]
 
−
|2018-2021
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|Physician's choice of:<br>1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br>2. [[#Eribulin_monotherapy|Eribulin]]<br>3. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br>4. [[#Paclitaxel_monotherapy.2C_weekly_3|Paclitaxel]]; weekly<br>5. [[#Paclitaxel_monotherapy.2C_q3wk_2|Paclitaxel]]; q3wk<br>6. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 23.9 vs 17.5 mo<br>(HR 0.64, 95% CI 0.48-0.86)
 
−
| style="background-color:#d73027" |Higher rate of pneumonitis
 
−
|-
 
−
|}
 
−
''Note: eribulin was the most commonly used comparator regimen.
 
−
====Prior treatment criteria====
 
−
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
 
−
====Biomarker eligibility criteria====
 
−
*DESTINY-Breast04: HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
 
−
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Trastuzumab deruxtecan (Enhertu)]] 5.4 mg/kg IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# '''DESTINY-Breast04:''' Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. [https://doi.org/10.1056/nejmoa2203690 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35665782/ PubMed] NCT03734029
 
−
 
−
==Vinorelbine monotherapy {{#subobject:5c104c|Regimen=1}}==
 
−
 
−
===Regimen variant #1, 25 mg/m<sup>2</sup> weekly {{#subobject:c0c952|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1994.12.10.2094 Gasparini et al. 1994]
 
−
|1991-1993
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(20011101)92:9%3C2267::aid-cncr1572%3E3.0.co;2-q Zelek et al. 2001]
 
−
|1997-1999
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-019-05280-2 Decker et al. 2019 (VicTORia)]
 
−
|2011-2016
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[Stub#Everolimus_.26_Vinorelbine|Everolimus & Vinorelbine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/j.ejca.2019.02.002 Yuan et al. 2019 (E7389-C086-304)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Eribulin_monotherapy|Eribulin]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|
 
−
|-
 
−
|Awaiting publication (TROPiCS-02)
 
−
|2019-2024
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Sacituzumab_govitecan_monotherapy_66|Sacituzumab govitecan]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
| style="background-color:#d73027" |Faster deterioration of global QoL
 
−
|-
 
−
|}
 
−
====Biomarker eligibility criteria====
 
−
*TROPiCS-02: HR+
 
−
====Chemotherapy====
 
−
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
−
'''21-day cycles'''
 
−
 
−
===Regimen variant #2, 30 mg/m<sup>2</sup> weekly {{#subobject:1b6c25|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1995.13.10.2567 Jones et al. 1995a]
 
−
|1990-1992
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Breast_cancer_-_historical#Melphalan_monotherapy_2|Melphalan]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.08.157 Keller et al. 2004]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Mitomycin_.26_Vinblastine_99|Mitomycin & Vinblastine]]<br> 2. [[#Pegylated_liposomal_doxorubicin_monotherapy_2|PLD]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
 
−
'''21-day cycles'''
 
−
 
−
===Regimen variant #3, 30 mg/m<sup>2</sup> q3wk {{#subobject:c63b68|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Bevacizumab_3|Capecitabine & Bevacizumab]]<br> 2. [[#Docetaxel_.26_Bevacizumab_2|Docetaxel & Bevacizumab]]<br> 3. [[#Gemcitabine_.26_Bevacizumab|Gemcitabine & Bevacizumab]]<br> 4. [[#Paclitaxel_.26_Bevacizumab_2|Paclitaxel & Bevacizumab]]<br> 5. [[#Paclitaxel.2C_nanoparticle_albumin-bound_.26_Bevacizumab_2|nab-Paclitaxel & Bevacizumab]] <br> 6. [[#Vinorelbine_.26_Bevacizumab|Vinorelbine & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===Regimen variant #4, 30 mg/m<sup>2</sup> 2 out of 3 weeks {{#subobject:7321fd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(07)70041-4 Martín et al. 2007 (GEICAM 2000-04)]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Gemcitabine_.26_Vinorelbine_88|Gemcitabine & Vinorelbine]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
−
'''21-day cycles'''
 
−
===References===
 
−
# Gasparini G, Caffo O, Barni S, Frontini L, Testolin A, Guglielmi RB, Ambrosini G. Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: a phase II study. J Clin Oncol. 1994 Oct;12(10):2094-101. [https://doi.org/10.1200/jco.1994.12.10.2094 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7931479 PubMed]
 
−
# Jones S, Winer E, Vogel C, Laufman L, Hutchins L, O'Rourke M, Lembersky B, Budman D, Bigley J, Hohneker J. Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer. J Clin Oncol. 1995 Oct;13(10):2567-74. [https://doi.org/10.1200/JCO.1995.13.10.2567 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7595708 PubMed]
 
−
# Zelek L, Barthier S, Riofrio M, Fizazi K, Rixe O, Delord JP, Le Cesne A, Spielmann M. Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma. Cancer. 2001 Nov 1;92(9):2267-72. [https://doi.org/10.1002/1097-0142(20011101)92:9%3C2267::aid-cncr1572%3E3.0.co;2-q link to original article] [https://pubmed.ncbi.nlm.nih.gov/11745280 PubMed]
 
−
# Keller AM, Mennel RG, Georgoulias VA, Nabholtz JM, Erazo A, Lluch A, Vogel CL, Kaufmann M, von Minckwitz G, Henderson IC, Mellars L, Alland L, Tendler C. Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. J Clin Oncol. 2004 Oct 1;22(19):3893-901. [https://doi.org/10.1200/JCO.2004.08.157 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15459210 PubMed]
 
−
# '''GEICAM 2000-04:''' Martín M, Ruiz A, Muñoz M, Balil A, García-Mata J, Calvo L, Carrasco E, Mahillo E, Casado A, García-Saenz JA, Escudero MJ, Guillem V, Jara C, Ribelles N, Salas F, Soto C, Morales-Vasquez F, Rodríguez CA, Adrover E, Mel JR; GEICAM. Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial. Lancet Oncol. 2007 Mar;8(3):219-25. [https://doi.org/10.1016/S1470-2045(07)70041-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17329192 PubMed] NCT00128310
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
−
# '''E7389-C086-304:''' Yuan P, Hu X, Sun T, Li W, Zhang Q, Cui S, Cheng Y, Ouyang Q, Wang X, Chen Z, Hiraiwa M, Saito K, Funasaka S, Xu B. Eribulin mesilate versus vinorelbine in women with locally recurrent or metastatic breast cancer: A randomised clinical trial. Eur J Cancer. 2019 May;112:57-65. Epub 2019 Mar 29. [https://doi.org/10.1016/j.ejca.2019.02.002 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30928806/ PubMed] NCT02225470
 
−
# '''VicTORia:''' Decker T, Marschner N, Muendlein A, Welt A, Hagen V, Rauh J, Schröder H, Jaehnig P, Potthoff K, Lerchenmüller C. VicTORia: a randomised phase II study to compare vinorelbine in combination with the mTOR inhibitor everolimus versus vinorelbine monotherapy for second-line chemotherapy in advanced HER2-negative breast cancer. Breast Cancer Res Treat. 2019 Aug;176(3):637-647. Epub 2019 May 21. [https://doi.org/10.1007/s10549-019-05280-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31115844 PubMed] NCT01520103
 
−
# '''ATTAIN:''' Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. [https://doi.org/10.1001/jamaoncol.2022.0514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100460/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35552364/ PubMed] NCT02915744
 
−
# '''EVER-132-002:''' NCT04639986
 
−
# '''TROPiCS-02:''' NCT03901339
 
−
 
−
==Vinorelbine & Bevacizumab {{#subobject:f3046|Regimen=1}}==
 
−
 
−
===Example orders===
 
−
*[[Example orders for Vinorelbine and Bevacizumab in breast cancer]]
 
−
 
−
===Regimen variant #1, vinorelbine 25 mg/m<sup>2</sup> weekly {{#subobject:82cbe7|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/14/23/7871.long Burstein et al. 2008]
 
−
|2001-2002
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
 
−
 
−
'''14-day cycles'''
 
−
 
−
===Regimen variant #2, vinorelbine 30 mg/m<sup>2</sup> q3wk {{#subobject:2b0f5d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.34.1255 Brufsky et al. 2011 (RIBBON-2)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Capecitabine_monotherapy_3|Capecitabine]]<br> 2. [[#Docetaxel_monotherapy_3|Docetaxel]]<br> 3. [[#Gemcitabine_monotherapy_2|Gemcitabine]]<br> 4. [[#Paclitaxel_monotherapy.2C_weekly_3|Paclitaxel]]; weekly<br> 5. [[#nab-Paclitaxel_monotherapy_3|nab-Paclitaxel]]<br> 6. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 7.2 vs 5.1 mo<br>(HR 0.78, 95% CI 0.64-0.93)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
 
−
'''21-day cycles'''
 
−
 
−
===References===
 
−
# Burstein HJ, Chen YH, Parker LM, Savoie J, Younger J, Kuter I, Ryan PD, Garber JE, Chen H, Campos SM, Shulman LN, Harris LN, Gelman R, Winer EP. VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin Cancer Res. 2008 Dec 1;14(23):7871-7. [http://clincancerres.aacrjournals.org/content/14/23/7871.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19047116 PubMed]
 
−
<!-- Presented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009, and at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
−
# '''RIBBON-2:''' Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2010.34.1255 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21990397 PubMed] NCT00281697
 
  
−
=Additional resources=
 
  
−
*[http://www.cancer.gov/bcrisktool/ Gail model Breast Cancer Risk Assessment Tool]
 
−
**[[Gail model breast cancer risk factors]]
 
−
*[[Breast cancer BRCA1 & BRCA2 genetic testing]]
 
−
*[http://www.adjuvantonline.com/index.jsp/ Adjuvant! Online (requires login)]
 
−
*[http://www.mycancergenome.org/content/disease/breast-cancer/ My Cancer Genome]
 
−
*[http://www.predict.nhs.uk/ PREDICT]
 
  
−
=Patient information=
+
Start of comment inserted by visual editor(edited again by visual editor)
−
*[http://www.lakeviewhealth.com/alcohol-increase-breast-cancer-risk-factors-infographic.php Alcohol and risk of breast cancer infographic]
 
  
−
[[Category:Breast cancer regimens]]
+
(edited again by visual editor end)End of comment inserted by visual editor
−
[[Category:Disease-specific pages]]
 
−
[[Category:Malignant breast neoplasm]]
 

Latest revision as of 14:51, 29 October 2023

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Forde et al. 2022 (CheckMate 816) 2017-2019 Phase 3 (C) 1a. CP & Nivolumab
1b. CVb & Nivolumab
1c. DC & Nivolumab 		Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. This study was conducted in the United States. The reason for the study was that an unanswered question at the time was whether adding an immune checkpoint inhibitor would improve outcomes.

Biomarker eligibility criteria

  • CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

21-day cycle for 3 cycles

Subsequent treatment

References

  1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528

Start of hidden/commented information for virtual editor End of hidden/commented information for virtual editor



Start of comment inserted by visual editor(edited again by visual editor)

(edited again by visual editor end)End of comment inserted by visual editor

Retrieved from "https://hemonc.org/w/index.php?title=Editing_test_page_2&oldid=79999"