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'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]]. If this is your first time visiting, we suggest you read the [[tutorial]].'''
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==Carboplatin & Paclitaxel (CP) {{#subobject:3a6h8q|Regimen=1}}==
 
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CP: '''<u>C</u>'''arboplatin & '''<u>P</u>'''aclitaxel
Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]]. ''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Breast_cancer_-_obsolete|obsolete regimens page]]. If you still can't find it, please let us know so we can add it!''
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<div class="toccolours" style="background-color:#eeeeee">
 
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===Regimen {{#subobject:1yg1q7|Variant=1}}===
*<big>Regimens for [[Breast_cancer,_HER2-positive|'''HER-2 receptor positive breast cancer are here''']]</big>.
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
*<big>Regimens for [[Breast_cancer,_triple_negative|'''Triple negative breast cancer (TNBC) are here''']]</big>.
+
!style="width: 20%"|Study
*''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.''
+
!style="width: 20%"|Dates of enrollment
 
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
{| class="wikitable" style="float:right; margin-right: 5px;"
+
!style="width: 20%"|Comparator
|-
+
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
 
<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
 
|}
 
{{TOC limit|limit=3}}
 
 
 
=Guidelines=
 
==[https://www.asco.org/ ASCO]==
 
*'''2016:''' [http://ascopubs.org/doi/full/10.1200/JCO.2016.67.1487 Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology guideline] [https://www.ncbi.nlm.nih.gov/pubmed/27217461 PubMed]
 
*'''2016:''' [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]
 
*'''2014:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876310/ Adjuvant endocrine therapy for women with hormone receptor–positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update]
 
 
 
==[http://www.esmo.org/ ESMO]==
 
*'''2015:''' [http://annonc.oxfordjournals.org/content/26/suppl_5/v8.full.pdf+html Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/26314782 PubMed]
 
*'''2011:''' [http://annonc.oxfordjournals.org/content/22/suppl_6/vi31.full.pdf+html BRCA in breast cancer: ESMO Clinical Practice Guidelines] [https://www.ncbi.nlm.nih.gov/pubmed/21908500 PubMed]
 
==ESO/ESMO==
 
===Current===
 
*'''2017:''' [http://www.thebreastonline.com/article/S0960-9776(16)30183-7/fulltext 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC3)] [https://www.ncbi.nlm.nih.gov/pubmed/27927580 PubMed]
 
 
 
===Older===
 
*'''2014:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176456/ ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2)] [https://www.ncbi.nlm.nih.gov/pubmed/25234545 PubMed]
 
 
 
==[https://www.nccn.org/ NCCN]==
 
*[https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf NCCN Guidelines - Breast Cancer]
 
 
 
=Neoadjuvant chemotherapy=
 
==AC {{#subobject:647f67|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
AC: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide
 
===Regimen {{#subobject:b18877|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70411-X/fulltext Robidoux et al. 2013 (NSABP B-41)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ Park et al. 2016 (I-SPY 2)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|-
 
|}
 
''Note: patients in '''NSABP B-41''' and '''I-SPY 2''' were HER2-positive.''
 
====Preceding treatment====
 
*'''I-SPY 2:''' [[Breast_cancer,_HER2-positive#Neratinib_.26_Paclitaxel|Neratinib & Paclitaxel]] x 12 wk versus [[Breast_cancer,_HER2-positive#TH_.28Taxol.29|TH]] x 12 wk
 
====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-41:''' [[Breast_cancer,_HER2-positive#TH_.28Taxol.29|TH]] versus [[Breast_cancer,_HER2-positive#THL_.28Taxol.29|THL]] versus [[Breast_cancer,_HER2-positive#TL_.28Taxol.29|TL]], then surgery
 
*'''I-SPY 2:''' Surgery
 
 
 
===References===
 
# Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70411-X/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24095300 PubMed]
 
<!-- Presented in part by Dr. Park at the 104th annual meeting of the American Association for Cancer Research, Washington, DC, April 6–10, 2013. -->
 
# Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. [http://www.nejm.org/doi/full/10.1056/NEJMoa1513750 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27406346 PubMed]
 
 
 
==ddAC {{#subobject:dcfdd2|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
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" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://jco.ascopubs.org/content/23/33/8340.long Burstein et al. 2005]
 
|style="background-color:#91cf60"|Non-randomized
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ Park et al. 2016 (I-SPY 2)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|-
 
|}
 
''Note: patients in '''I-SPY 2''' were HER2-positive.''
 
====Preceding treatment====
 
*'''I-SPY 2:''' [[Breast_cancer,_HER2-positive#Neratinib_.26_Paclitaxel|Neratinib & Paclitaxel]] x 12 wk versus [[Breast_cancer,_HER2-positive#TH_.28Taxol.29|TH]] x 12 wk
 
====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 medications====
 
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2, given 24 hours after chemotherapy
 
*'''Burstein et al. 2005:''' [[Darbepoetin alfa (Aranesp)]] 200 mcg SC once on day 1 for patients with Hb 10 to 12 g/dL; see paper for additional dose adjustments
 
 
 
'''14-day cycle for 4 cycles'''
 
====Subsequent treatment====
 
*'''Burstein et al. 2005:''' Optional [[#Paclitaxel_monotherapy|Neoaduvant paclitaxel]], then surgery or surgery, then [[#Paclitaxel_monotherapy_2|adjuvant paclitaxel]]; this was not a randomization
 
*'''I-SPY 2:''' 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. [http://jco.ascopubs.org/content/23/33/8340.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16293865 PubMed]
 
<!-- Presented in part by Dr. Park at the 104th annual meeting of the American Association for Cancer Research, Washington, DC, April 6–10, 2013. -->
 
# Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. [http://www.nejm.org/doi/full/10.1056/NEJMoa1513750 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27406346 PubMed]
 
 
 
==Docetaxel monotherapy {{#subobject:1216fd|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
D: '''<u>D</u>'''ocetaxel
 
<br>T: '''<u>T</u>'''axotere (Docetaxel)
 
===Regimen {{#subobject:5b038d|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70137-3/fulltext Earl et al. 2015 (ARTemis)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]]
 
|style="background-color:#fc8d59"|Seems to have inferior pCR rate
 
|-
 
|}
 
====Chemotherapy====
 
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 
 
 
'''21-day cycle for 3 cycles'''
 
====Subsequent treatment====
 
*[[#FEC|FEC]]
 
 
 
===References===
 
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70137-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25975632 PubMed]
 
 
 
==Docetaxel & Bevacizumab {{#subobject:23b667|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
Bev+D: '''<u>Bev</u>'''acizumab and '''<u>D</u>'''ocetaxel
 
===Regimen {{#subobject:a2a6a4|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70137-3/fulltext Earl et al. 2015 (ARTemis)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Docetaxel_monotherapy|Docetaxel]]
 
|style="background-color:#91cf60"|Seems to have superior pCR rate
 
|-
 
|}
 
''Note: a total of four bevacizumab doses are given, with the fourth given with the first cycle of FEC.''
 
====Chemotherapy====
 
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 
 
 
'''21-day cycle for 3 cycles'''
 
 
 
====Subsequent treatment====
 
*[[#FEC|FEC]]
 
 
 
===References===
 
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70137-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25975632 PubMed]
 
 
 
==EC {{#subobject:3e1e8f|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
EC: '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide
 
===Regimen {{#subobject:da3717|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00542-2/abstract Untch et al. 2016 (GBG 69)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|-
 
|}
 
====Preceding treatment====
 
*[[#Paclitaxel.2C_nanoparticle_albumin-bound_monotherapy|nab-Paclitaxel]] x 4 versus [[#Paclitaxel_monotherapy_2|Paclitaxel]] x 4
 
====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====
 
*Surgery
 
 
 
===References===
 
# 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 (GBG).; 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00542-2/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26869049 PubMed]
 
 
 
==FEC {{#subobject:ec48df|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
FEC: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide
 
===Regimen {{#subobject:a74d5d|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70137-3/fulltext Earl et al. 2015 (ARTemis)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|-
 
|}
 
''Note that for the patients randomized to the bevacizumab arm, a fourth dose was given with the first cycle of FEC.''
 
====Preceding treatment====
 
*[[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]] x 3 versus [[#Docetaxel_monotherapy|Docetaxel]] x 3
 
 
 
====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 3 cycles'''
 
====Subsequent treatment====
 
*Surgery
 
 
 
===References===
 
# Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005 Jun 1;23(16):3676-85. Epub 2005 Feb 28. [http://jco.ascopubs.org/content/23/16/3676.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15738535 PubMed]
 
## '''Update:''' Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007 Jan 1;13(1):228-33. [http://clincancerres.aacrjournals.org/content/13/1/228.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17200359 PubMed]
 
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70137-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25975632 PubMed]
 
 
 
==Paclitaxel monotherapy {{#subobject:f579fb|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
T: '''<u>T</u>'''axol (Paclitaxel)
 
===Regimen #1, weekly paclitaxel {{#subobject:c345c9|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00542-2/fulltext Untch et al. 2016 (GBG 69)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel.2C_nanoparticle_albumin-bound_monotherapy|nab-Paclitaxel]]
 
|style="background-color:#d73027"|Inferior pCR rate
 
|-
 
|}
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
 
 
'''21-day cycle for 4 cycles'''
 
 
 
====Subsequent treatment====
 
*[[#EC|EC]]
 
 
 
===Regimen #2, bi-weekly paclitaxel {{#subobject:b5be66|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/23/33/8340.long Burstein et al. 2005]
 
|style="background-color:#91cf60"|Non-randomized
 
|
 
|
 
|-
 
|rowspan=2|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70554-0/fulltext Earl et al. 2013 (Neo-tAnGo)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|EC, then T<br> EC, then TG
 
|style="background-color:#91cf60"|Seems to have superior pCR rate
 
|-
 
|TG
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Preceding treatment====
 
*'''Burstein et al. 2005:''' [[#ddAC|ddAC]] x 4
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 
 
 
'''14-day cycle for 4 cycles'''
 
====Subsequent treatment====
 
*'''Burstein et al. 2005:''' Surgery
 
*'''Neo-tAnGo:''' [[#EC|EC]]
 
 
 
===References===
 
# Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005 Jun 1;23(16):3676-85. Epub 2005 Feb 28. [http://jco.ascopubs.org/content/23/16/3676.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15738535 PubMed]
 
## '''Update:''' Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007 Jan 1;13(1):228-33. [http://clincancerres.aacrjournals.org/content/13/1/228.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17200359 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. [http://jco.ascopubs.org/content/23/33/8340.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16293865 PubMed]
 
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70554-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24360787 PubMed]
 
# 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 (GBG).; 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00542-2/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26869049 PubMed]
 
 
 
==Paclitaxel, nanoparticle albumin-bound monotherapy {{#subobject:8f6227|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:fe2978|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00542-2/abstract Untch et al. 2016 (GBG 69)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel_monotherapy_2|Paclitaxel]]
 
|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)]] 125 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
 
 
'''21-day cycle for 4 cycles'''
 
 
 
====Subsequent treatment====
 
*[[#EC|EC]]
 
 
 
===References===
 
# 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 (GBG).; 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00542-2/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26869049 PubMed]
 
 
 
=Neoadjuvant endocrine therapy=
 
==Anastrozole & Goserelin {{#subobject:6e3249|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:a131ba|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70373-4/fulltext Masuda et al. 2012 (STAGE)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Goserelin_.26_Tamoxifen|Goserelin & Tamoxifen]]
 
|style="background-color:#1a9850"|Superior RR
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
*[[Goserelin (Zoladex)]] 3.6 mg IM depot once per month
 
 
 
'''24-week course'''
 
====Subsequent treatment====
 
*Surgery
 
 
 
===References===
 
# Masuda N, Sagara Y, Kinoshita T, Iwata H, Nakamura S, Yanagita Y, Nishimura R, Iwase H, Kamigaki S, Takei H, Noguchi S. Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial. Lancet Oncol. 2012 Apr;13(4):345-52. Epub 2012 Jan 20. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70373-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22265697 PubMed]
 
 
 
==Goserelin & Tamoxifen {{#subobject:23ef1e|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:833f0d|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70373-4/fulltext Masuda et al. 2012 (STAGE)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Goserelin_.26_Tamoxifen|Goserelin & Tamoxifen]]
 
|style="background-color:#d73027"|Inferior RR
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Goserelin (Zoladex)]] 3.6 mg IM depot once per month
 
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
 
 
'''24-week course'''
 
====Subsequent treatment====
 
*Surgery
 
===References===
 
# Masuda N, Sagara Y, Kinoshita T, Iwata H, Nakamura S, Yanagita Y, Nishimura R, Iwase H, Kamigaki S, Takei H, Noguchi S. Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial. Lancet Oncol. 2012 Apr;13(4):345-52. Epub 2012 Jan 20. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70373-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22265697 PubMed]
 
 
 
=Neoadjuvant response criteria=
 
 
 
==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/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://ascopubs.org/doi/full/10.1200/JCO.2007.10.6823 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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%2Fs10434-014-3922-0 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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=
 
 
 
==AC {{#subobject:77b0fd|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
AC: '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide
 
<br>CA: '''<u>C</u>'''yclophosphamide and '''<u>A</u>'''driamycin (Doxorubicin)
 
===Regimen #1 {{#subobject:ac3513|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/19/4/931.full Fisher et al. 2001 (NSABP B-23)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#CMF|CMF]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://jco.ascopubs.org/content/21/6/976.long Henderson et al. 2003 (INT 0148/CALGB 9344)]
 
|style="background-color:#1a9850"|Phase III
 
|High-dose AC<br> Very-high-dose AC
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://jco.ascopubs.org/content/21/8/1431.long Citron et al. 2003 (CALGB 9741)]
 
|style="background-color:#1a9850"|Phase III
 
|A<br> ddA<br> [[#ddAC_2|ddAC]]
 
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pubmed/14715110 Van Pelt et al. 2003]
 
|style="background-color:#91cf60"|Phase II
 
|
 
|
 
|-
 
|[http://jco.ascopubs.org/content/23/16/3686.long Mamounas et al. 2005 (NSABP B-28)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|
 
|
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052122 Romond et al. 2005 (NSABP B-31/NCCTG N9831)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|
 
|
 
|-
 
|[http://jco.ascopubs.org/content/24/34/5381.full Jones et al. 2006 (US Oncology Trial 9735)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#TC_.28Taxotere.29|TC]]
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ Sparano et al. 2008 (ECOG E1199)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|
 
|
 
|-
 
|[http://jco.ascopubs.org/content/29/29/3877.long Eiermann et al. 2011 (BCIRG-005)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BCIRG-005|See link]]
 
|[[Complex_multipart_regimens#BCIRG-005|See link]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268553/ Slamon et al. 2011 (BCIRG 006)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BCIRG_006|See link]]
 
|[[Complex_multipart_regimens#BCIRG_006|See link]]
 
|-
 
|}
 
''Patients in '''Van Pelt et al. 2003''', '''NSABP B-31''', '''NCCTG N9831''', and '''BCIRG 006''' were HER2-positive.''
 
====Preceding treatment====
 
*'''Van Pelt et al. 2003:''' [[Breast_cancer,_HER2-positive#TH_.28Taxotere.29|Neoadjuvant TH]], then surgery
 
*'''INT 0148/CALGB 9344:''' 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:''' [[#Tamoxifen_monotherapy|Tamoxifen]] versus [[#Placebo|placebo]]
 
*'''Van Pelt et al. 2003:''' [[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy|H]]
 
*'''INT 0148/CALGB 9344''' and '''NSABP B-28:''' [[#Paclitaxel_monotherapy_2|T (Taxol)]] versus [[Breast_cancer_-_obsolete#Observation|no further therapy]]
 
*'''CALGB 9741:''' [[#Paclitaxel_monotherapy_2|T (Taxol)]]
 
*'''NSABP B-31:''' [[#Paclitaxel_monotherapy_2|T (Taxol)]] versus [[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH (Taxol)]]
 
*'''NCCTG N9831:''' [[#Paclitaxel_monotherapy_2|T (Taxol)]] versus [[#Paclitaxel_monotherapy_2|T (Taxol)]], then [[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy|H]] versus [[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH (Taxol)]]
 
*'''ECOG E1199:''' [[#Docetaxel_monotherapy_2|Docetaxel q3wk]] versus [[#Docetaxel_monotherapy_2|Docetaxel weekly]] versus [[#Paclitaxel_monotherapy_2|Paclitaxel q3wk]] versus [[#Paclitaxel_monotherapy_2|Paclitaxel weekly]]
 
*'''BCIRG-005:''' [[#Docetaxel_monotherapy_2|T (Taxotere)]]
 
*'''BCIRG 006:''' [[#Paclitaxel_monotherapy_2|T (Taxol)]] versus [[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH (Taxol)]]
 
 
 
===Regimen #2, with range {{#subobject:67eda7|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|-
 
|}
 
''Patients in '''APHINITY''' had HER2-positive breast cancer. Note that ranges for AC are given in the protocol, replicated here.''
 
====Preceding treatment====
 
*Surgery
 
====Chemotherapy====
 
*[[Doxorubicin (Adriamycin)]] 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 4 cycles'''
 
====Subsequent treatment====
 
*[[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH (Taxol)]] versus [[Breast_cancer,_HER2-positive#THP_.28Taxol.29_2|THP (Taxol)]] or [[Breast_cancer,_HER2-positive#TH_.28Taxotere.29_2|TH (Taxotere)]] versus [[Breast_cancer,_HER2-positive#THP_.28Taxotere.29_2|THP (Taxotere)]]
 
===References===
 
# 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. [http://jco.ascopubs.org/content/19/4/931.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11181655 PubMed]
 
# 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. [http://jco.ascopubs.org/content/21/6/976.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12637460 PubMed]
 
# 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. [http://jco.ascopubs.org/content/21/8/1431.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12668651 PubMed]
 
# Van Pelt AE, Mohsin S, Elledge RM, Hilsenbeck SG, Gutierrez MC, Lucci A Jr, Kalidas M, Granchi T, Scott BG, Allred DC, Chang JC. Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results. Clin Breast Cancer. 2003 Dec;4(5):348-53. [https://www.ncbi.nlm.nih.gov/pubmed/14715110 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. -->
 
# 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. [http://jco.ascopubs.org/content/23/16/3686.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15897552 PubMed]
 
<!-- no pre-pub disclosed -->
 
# Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. [http://www.nejm.org/doi/full/10.1056/NEJMoa052122 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16236738 PubMed]
 
## '''Update:''' Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4491-7. Epub 2011 Oct 31. [http://ascopubs.org/doi/full/10.1200/JCO.2011.36.7045 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236650/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22042958 PubMed]
 
## '''Update:''' Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. [http://ascopubs.org/doi/full/10.1200/JCO.2014.55.5730 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226805/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25332249 PubMed]
 
# 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. [http://jco.ascopubs.org/content/24/34/5381.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/27/8/1177.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19204201 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. -->
 
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa0707056 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18420499 PubMed]
 
## '''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. [http://jco.ascopubs.org/content/33/21/2353.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500829/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26077235 PubMed]
 
# Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martin 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. [http://jco.ascopubs.org/content/29/29/3877.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21911726 PubMed]
 
<!-- no pre-pub disclosed -->
 
# Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. [http://www.nejm.org/doi/full/10.1056/NEJMoa0910383 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268553/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21991949 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.30421/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28081304 PubMed]
 
# von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [http://www.nejm.org/doi/full/10.1056/NEJMoa1703643 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''contains verified protocol in supplementary protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28581356 PubMed]
 
 
 
==Capecitabine monotherapy {{#subobject:e058c1|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen #1, 4 cycles {{#subobject:36e4ba|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489700/ Cameron et al. 2017 (TACT2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#TACT2|See link]]
 
|[[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 BID on days 1 to 14
 
 
 
'''21-day cycle for 4 cycles'''
 
 
 
===Regimen #2, 6 to 8 cycles {{#subobject:9cc782|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1612645 Masuda et al. 2017]
 
|style="background-color:#1a9850"|Phase III
 
|Standard therapy
 
|style="background-color:#1a9850"|Superior OS
 
|-
 
|}
 
''All patients in this study had residual disease at time of surgical resection. Concomitant endocrine therapy was allowed.''
 
====Preceding treatment====
 
*Neoadjuvant chemotherapy containing anthracycline, taxane, or both, then surgery
 
====Chemotherapy====
 
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO BID on days 1 to 14
 
 
 
'''21-day cycle for 6 to 8 cycles'''
 
 
 
===References===
 
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1612645 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28564564 PubMed]
 
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30404-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489700/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28600210 PubMed]
 
 
 
==CMF {{#subobject:fb4c46|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
CMF: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
 
 
===Regimen #1, IV cyclophosphamide {{#subobject:831237|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/25/18/2509.long Schmid et al. 2007 (TABLE)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer#Leuprolide_monotherapy|Leuprolide]]
 
|style="background-color:#d73027"|Inferior OS
 
|-
 
|}
 
====Preceding treatment====
 
*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 #2, classic CMF (IV) x 6 {{#subobject:958ae2|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052084 Poole et al. 2006 (NEAT)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer#Epirubicin_monotherapy|Epirubicin]], then CMF x 4
 
|style="background-color:#d73027"|Inferior OS
 
|-
 
|}
 
====Preceding treatment====
 
*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 #3, classic CMF (PO) x 6 {{#subobject:dcd1f4|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/16/8/2651.long Levine et al. 1998 (NCIC CTG MA5)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer#FEC_2|CEF]]
 
|style="background-color:#d73027"|Inferior RFS
 
|-
 
|[http://jco.ascopubs.org/content/19/4/931.full Fisher et al. 2001 (NSABP B-23)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer#AC|AC]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/19/12/3103.long Piccart et al. 2001]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer#EC_2|Full-dose EC]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[[Breast_cancer#EC_2|Moderate-dose EC]]
 
|Not reported
 
|-
 
|[http://jco.ascopubs.org/content/23/33/8313.long Hutchins et al. 2005 (INT-0102)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer#FAC|CAF]]
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052084 Poole et al. 2006 (NEAT)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer#Epirubicin_monotherapy|Epirubicin]], then CMF x 4
 
|style="background-color:#d73027"|Inferior OS
 
|-
 
|}
 
====Preceding treatment====
 
*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#Tamoxifen_monotherapy|tamoxifen]] x 5 years versus [[Breast_cancer#Placebo|placebo]]
 
 
 
===Regimen #4, classic CMF (PO) x 4 {{#subobject:114f05|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052084 Poole et al. 2006 (NEAT)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BR9601|See link]]
 
|[[Complex_multipart_regimens#BR9601|See link]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489700/ Cameron et al. 2017 (TACT2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#TACT2|See link]]
 
|[[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====
 
*[[#Epirubicin_monotherapy_2|Epirubicin]] x 4
 
====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 4 cycles'''
 
 
 
===Regimen #5, classic CMF (IV) x 4 {{#subobject:37c8be|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052084 Poole et al. 2006 (NEAT)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BR9601|See link]]
 
|[[Complex_multipart_regimens#BR9601|See link]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489700/ Cameron et al. 2017 (TACT2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#TACT2|See link]]
 
|[[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====
 
*[[#Epirubicin_monotherapy_2|Epirubicin]] 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 #6, modified CMF x 4 {{#subobject:98f74e|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052084 Poole et al. 2006 (BR9601)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BR9601|See link]]
 
|[[Complex_multipart_regimens#BR9601|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====
 
*[[#Epirubicin_monotherapy_2|Epirubicin]] x 4
 
====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 4 cycles'''
 
 
 
===Regimen #7, modified CMF x 8 {{#subobject:7a96ee|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052084 Poole et al. 2006 (BR9601)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Epirubicin_monotherapy|Epirubicin]], then CMF x 4
 
|style="background-color:#d73027"|Inferior OS
 
|-
 
|}
 
====Preceding treatment====
 
*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 8 cycles'''
 
 
 
===Regimen #8, classic CMF x 12 {{#subobject:8a712c|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJM197602192940801 Bonadonna et al. 1976]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer_-_obsolete#Observation|Observation]]
 
|style="background-color:#1a9850"|Superior RFS
 
|-
 
|}
 
====Preceding treatment====
 
*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. [http://www.nejm.org/doi/full/10.1056/NEJM197602192940801 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197706)39:6%3C2904::AID-CNCR2820390677%3E3.0.CO;2-8/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/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. [http://www.nejm.org/doi/ref/10.1056/NEJM199504063321401 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7877646 PubMed]
 
# 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://www.ncbi.nlm.nih.gov/pubmed/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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.24969/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20186830 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2403834 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. 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. The International Collaborative Cancer Group. J Clin Oncol. 1996 Jan;14(1):35-45. [http://ascopubs.org/doi/full/10.1200/JCO.1996.14.1.35 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8558217 PubMed]
 
# '''Review:''' Goldhirsch A, Colleoni M, Coates AS, Castiglione-Gertsch M, Gelber RD. Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all CMFs alike? The International Breast Cancer Study Group (IBCSG). Ann Oncol. 1998 May;9(5):489-93. [http://annonc.oxfordjournals.org/content/9/5/489.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9653488 PubMed]
 
# 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. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1998 Aug;16(8):2651-8. [http://jco.ascopubs.org/content/16/8/2651.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://ascopubs.org/doi/full/10.1200/JCO.2005.09.423 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16051958 PubMed]
 
# 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. [http://jco.ascopubs.org/content/19/4/931.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11181655 PubMed]
 
# 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. [http://jco.ascopubs.org/content/19/12/3103.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408507 PubMed]
 
# 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. [http://jco.ascopubs.org/content/23/33/8313.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16293862 PubMed]
 
<!-- no pre-pub disclosed -->
 
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa052084 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17079759 PubMed]
 
# 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. [http://www.ejcancer.com/article/S0959-8049(07)00014-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17306974 PubMed]
 
<!-- 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. -->
 
# 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. [http://jco.ascopubs.org/content/25/18/2509.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17577027 PubMed]
 
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60740-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687939/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19447249 PubMed]
 
 
 
==CMFT {{#subobject:acff18|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
CMFT: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>T</u>'''amoxifen
 
===Regimen {{#subobject:9f63d1|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://www.ejcancer.com/article/S0959-8049(13)00383-3/fulltext Eljertsen et al. 2013 (DBCG 82C)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#Tamoxifen_monotherapy|Tamoxifen]]
 
|style="background-color:#1a9850"|Superior DFS
 
|-
 
|Tamoxifen & RT
 
|Not reported
 
|-
 
|}
 
====Preceding treatment====
 
*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
 
*[[Tamoxifen (Nolvadex)]] 30 mg PO once per day
 
 
 
'''28-day cycle for 9 cycles (tamoxifen continued for one year total)'''
 
 
 
===References===
 
# 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. [http://www.ejcancer.com/article/S0959-8049(13)00383-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23756360 PubMed]
 
 
 
==DC {{#subobject:faf430|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
DC: '''<u>D</u>'''ocetaxel and '''<u>C</u>'''yclophosphamide
 
===Regimen {{#subobject:9d832b|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2017.72.3494 Ejlertsen et al. 2017 (DBCG 07-READ)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#EC_2|EC]], then [[#Docetaxel_monotherapy_2|D]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
''Patients were TOP2A normal as determined by FISH.''
 
====Preceding treatment====
 
*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===
 
# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.3494 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28661759 PubMed]
 
 
 
==ddA {{#subobject:c9fa7d|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
ddA: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin)
 
===Regimen {{#subobject:90fd28|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/21/8/1431.long Citron et al. 2003 (CALGB 9741)]
 
|style="background-color:#1a9850"|Phase III
 
|[[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]
 
|style="background-color:#91cf60"|Phase II
 
|
 
|
 
|-
 
|}
 
''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
 
====Chemotherapy====
 
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
 
 
====Supportive medications====
 
*[[Filgrastim (Neupogen)]]
 
 
 
'''14-day cycle for 4 cycles'''
 
====Subsequent treatment====
 
*[[#ddT_.28Taxol.29|ddT]]
 
 
 
===References===
 
# 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. [http://jco.ascopubs.org/content/21/8/1431.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12668651 PubMed]
 
# 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://www.ncbi.nlm.nih.gov/pubmed/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. [http://content.karger.com/produktedb/produkte.asp?DOI=000315734&typ=pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20523088 PubMed]
 
 
 
==ddAC {{#subobject:b52056|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
ddAC: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide
 
===Regimen {{#subobject:cdafd0|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/21/8/1431.long Citron et al. 2003 (CALGB 9741)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
|-
 
|[http://jco.ascopubs.org/content/23/33/8340.long Burstein et al. 2005]
 
|style="background-color:#91cf60"|Non-randomized
 
|
 
|
 
|-
 
|[http://jco.ascopubs.org/content/26/8/1216.long Dang et al. 2008]
 
|style="background-color:#91cf60"|Phase II
 
|
 
|
 
|-
 
|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ Shulman et al. 2012 (CALGB 40101)]
 
|rowspan=3 style="background-color:#1a9850"|Phase III
 
|ddAC x 6
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[[#Paclitaxel_monotherapy_2|Paclitaxel x 4]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Paclitaxel x 6
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ Swain et al. 2013 (NSABP B-38)]
 
|style="background-color:#1a9850"|Phase III
 
|[[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. Patients in '''Dang et al. 2008''' had HER2-positive breast cancer.''
 
====Preceding treatment====
 
*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 medications====
 
*(varies depending on reference):
 
*'''CALGB 9741:'''
 
**[[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).
 
*'''Burstein et al. 2005''' and '''Dang et al. 2008:'''
 
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2, given 24 hours after chemotherapy
 
*'''Burstein et al. 2005:'''
 
**[[Darbepoetin alfa (Aranesp)]] 200 mcg SC once on day 1 for patients with Hb 10 to 12 g/dL; 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 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 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, administered once 24 to 36 hours after chemotherapy
 
 
 
'''14-day cycle for 4 cycles'''
 
 
 
====Subsequent treatment====
 
*'''CALGB 9741''' and '''Burstein et al. 2005:''' [[#Paclitaxel_monotherapy_2|Paclitaxel]] x 4
 
*'''Dang et al. 2008:''' [[Breast_cancer,_HER2-positive#ddTH_.28Taxol.29|ddTH (Taxol)]]
 
*'''NSABP B-38:''' [[#ddT_.28Taxol.29|dose-dense paclitaxel]] x 4 versus ddPG x 4
 
 
 
===Regimen #2, with range {{#subobject:b6d1ca|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|-
 
|}
 
''Patients in '''APHINITY''' had HER2-positive breast cancer. Note that ranges for ddAC are given in the protocol, replicated here.''
 
====Preceding treatment====
 
*Surgery
 
====Chemotherapy====
 
*[[Doxorubicin (Adriamycin)]] 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
 
 
 
====Supportive medications====
 
*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified)
 
 
 
'''14-day cycle for 4 cycles'''
 
====Subsequent treatment====
 
*[[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH (Taxol)]] versus [[Breast_cancer,_HER2-positive#THP_.28Taxol.29_2|THP (Taxol)]] or [[Breast_cancer,_HER2-positive#TH_.28Taxotere.29_2|TH (Taxotere)]] versus [[Breast_cancer,_HER2-positive#THP_.28Taxotere.29_2|THP (Taxotere)]]
 
===References===
 
# 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. [http://jco.ascopubs.org/content/21/8/1431.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12668651 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. [http://jco.ascopubs.org/content/23/33/8340.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16293865 PubMed]
 
# Dang C, Fornier M, Sugarman S, Troso-Sandoval T, Lake D, D'Andrea G, Seidman A, Sklarin N, Dickler M, Currie V, Gilewski T, Moynahan ME, Drullinsky P, Robson M, Wasserheit-Leiblich C, Mills N, Steingart R, Panageas K, Norton L, Hudis C. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer. J Clin Oncol. 2008 Mar 10;26(8):1216-22. [http://jco.ascopubs.org/content/26/8/1216.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18323546 PubMed]
 
# 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. [http://jco.ascopubs.org/content/30/33/4071.long link to original article] '''contains verified protocol''' [http://jco.ascopubs.org/content/suppl/2012/07/23/JCO.2011.40.6405.DC1/Protocol.pdf link to study protocol PDF] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22826271 PubMed]
 
## '''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://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105484/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24934787 PubMed]
 
# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2012.48.1275 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23940225 PubMed]
 
# von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [http://www.nejm.org/doi/full/10.1056/NEJMoa1703643 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''contains verified protocol in supplementary protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28581356 PubMed]
 
 
 
==ddC {{#subobject:2ba5c2|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
ddC: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>C</u>'''yclophosphamide
 
===Regimen #1, 600 mg/m<sup>2</sup> {{#subobject:6f231e|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/21/8/1431.long Citron et al. 2003 (CALGB 9741)]
 
|style="background-color:#1a9850"|Phase III
 
|[[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====
 
*[[#ddT_.28Taxol.29|ddT]] x 4
 
====Chemotherapy====
 
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
 
 
====Supportive medications====
 
*[[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 #2, 800 mg/m<sup>2</sup> {{#subobject:822b10|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.karger.com/Article/Abstract/86987 Kahan et al. 2005]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
''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====
 
*[[#ddT_.28Taxol.29|ddT]] x 4
 
====Chemotherapy====
 
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1
 
 
 
====Supportive medications====
 
*[[Filgrastim (Neupogen)]]
 
 
 
'''14-day cycle for 4 cycles'''
 
 
 
===References===
 
# 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. [http://jco.ascopubs.org/content/21/8/1431.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12668651 PubMed]
 
# 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://www.ncbi.nlm.nih.gov/pubmed/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. [http://content.karger.com/produktedb/produkte.asp?DOI=000315734&typ=pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20523088 PubMed]
 
 
 
==ddEC {{#subobject:824585|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
ddEC: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide
 
===Regimen #1, with range {{#subobject:d9d108|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|-
 
|}
 
''Patients in '''APHINITY''' had HER2-positive breast cancer. Note that ranges for ddEC are given in the protocol, replicated here.''
 
====Preceding treatment====
 
*Surgery
 
====Chemotherapy====
 
*[[Epirubicin (Ellence)]] 90 to 120 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
 
 
 
====Supportive medications====
 
*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified)
 
 
 
'''14-day cycle for 4 cycles'''
 
====Subsequent treatment====
 
*[[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH (Taxol)]] versus [[Breast_cancer,_HER2-positive#THP_.28Taxol.29_2|THP (Taxol)]] or [[Breast_cancer,_HER2-positive#TH_.28Taxotere.29_2|TH (Taxotere)]] versus [[Breast_cancer,_HER2-positive#THP_.28Taxotere.29_2|THP (Taxotere)]]
 
 
 
===Regimen #2 {{#subobject:aa6006|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62048-1/fulltext Del Mastro et al. 2015 (GIM2)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#ddFEC|ddFEC]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[[#EC_2|EC]]<br> [[#FEC_2|FEC]]
 
|style="background-color:#1a9850"|Superior OS
 
|-
 
|}
 
''To be completed; insufficient details in abstract for dosing.''
 
====Preceding treatment====
 
*Surgery
 
====Chemotherapy====
 
*[[Epirubicin (Ellence)]]
 
*[[Cyclophosphamide (Cytoxan)]]
 
====Supportive medications====
 
*[[Pegfilgrastim (Neulasta)]]
 
====Subsequent treatment====
 
*[[#Paclitaxel_monotherapy_2|Paclitaxel]]
 
 
 
===References===
 
# 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 (GIM) investigators. 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62048-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25740286 PubMed]
 
# von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [http://www.nejm.org/doi/full/10.1056/NEJMoa1703643 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''contains verified protocol in supplementary protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28581356 PubMed]
 
 
 
==ddFEC {{#subobject:45dbc1|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
ddFEC: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide
 
===Regimen {{#subobject:05e37f|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
|style="width: 20%"!Study
 
|style="width: 20%"![[Levels_of_Evidence#Evidence|Evidence]]
 
|style="width: 20%"!Comparator
 
|style="width: 20%"![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[https://academic.oup.com/annonc/article/27/10/1873/2389052 Mavroudis et al. 2016 (HORG CT/07.17)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#HORG_CT.2F07.17|See link]]
 
|[[Complex_multipart_regimens#HORG_CT.2F07.17|See link]]
 
|-
 
|}
 
====Preceding treatment====
 
*Surgery
 
====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
 
 
 
====Supportive medications====
 
*[[: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'''
 
====Subsequent treatment====
 
*[[#Docetaxel_monotherapy_2|Docetaxel]]
 
 
 
===References===
 
# Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; Breast Cancer Investigators of the Hellenic Oncology Research Group (HORG), Athens, Greece. 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://academic.oup.com/annonc/article/27/10/1873/2389052 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27502729 PubMed]
 
 
 
==ddT (Taxol) {{#subobject:8acb30|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
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 #1, 175 mg/m<sup>2</sup> {{#subobject:d853ac|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/21/8/1431.long Citron et al. 2003 (CALGB 9741)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
|[[Complex_multipart_regimens#CALGB_9741|See link]]
 
|-
 
|[http://jco.ascopubs.org/content/23/33/8340.long Burstein et al. 2005]
 
|style="background-color:#91cf60"|Non-randomized
 
|
 
|
 
|-
 
|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ Shulman et al. 2012 (CALGB 40101)]
 
|rowspan=3 style="background-color:#1a9850"|Phase III
 
|[[#ddAC_2|ddAC]] x 4
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|ddAC x 6
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|ddT x 6
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ Swain et al. 2013 (NSABP B-38)]
 
|style="background-color:#1a9850"|Phase III
 
|[[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:''' [[#ddA|ddA]] x 4 or [[#ddAC_2|ddAC]] x 4
 
*'''Burstein et al. 2005:''' [[#ddAC|Neoadjuvant ddAC]] and surgery or [[#ddAC_2|adjuvant ddAC]]
 
*'''CALGB 40101:''' Surgery, within 90 days
 
*'''NSABP B-38:''' [[#ddAC_2|ddAC]] x 4
 
 
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
 
 
====Supportive medications====
 
*[[Diphenhydramine (Benadryl)]] 12.5 to 50 mg IV 30 to 60 minutes prior to paclitaxel
 
*One of the following H2 blockers:
 
**[[Ranitidine (Zantac)]] 50 mg IV 30 to 60 minutes prior to paclitaxel
 
**[[Cimetidine (Tagamet)]] 300 mg IV 30 to 60 minutes prior to paclitaxel
 
**[[Famotidine (Pepcid)]] 20 mg IV 30 to 60 minutes prior to paclitaxel
 
*One of the following dexamethasone choices:
 
**[[Dexamethasone (Decadron)]] 10 mg IV less than 60 minutes prior to paclitaxel
 
**[[Dexamethasone (Decadron)]] 10 mg PO greater than 60 minutes prior to paclitaxel
 
**[[Dexamethasone (Decadron)]] 20 mg PO 6 hours and 12 hour prior to paclitaxel
 
*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, administered once 24 to 36 hours after chemotherapy
 
 
 
'''14-day cycle for 4 cycles'''
 
 
 
====Subsequent treatment====
 
*'''CALGB 9741:''' [[#ddC|ddC]] x 4 (if preceded by ddA)
 
 
 
===Regimen #2, 200 mg/m<sup>2</sup> {{#subobject:6a0bb6|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.karger.com/Article/Abstract/86987 Kahan et al. 2005]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
''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====
 
*[[#ddA|ddA]] x 4
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours day 1
 
 
 
====Supportive medications====
 
*[[Filgrastim (Neupogen)]]
 
 
 
'''14-day cycle for 4 cycles'''
 
====Subsequent treatment====
 
*[[#ddC|ddC]]
 
 
 
===References===
 
# 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. [http://jco.ascopubs.org/content/21/8/1431.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12668651 PubMed]
 
# 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://www.ncbi.nlm.nih.gov/pubmed/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. [http://content.karger.com/produktedb/produkte.asp?DOI=000315734&typ=pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/23/33/8340.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16293865 PubMed]
 
# 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. [http://jco.ascopubs.org/content/30/33/4071.long link to original article] '''contains verified protocol''' [http://jco.ascopubs.org/content/suppl/2012/07/23/JCO.2011.40.6405.DC1/Protocol.pdf link to study protocol PDF] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22826271 PubMed]
 
## '''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://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105484/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24934787 PubMed]
 
# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2012.48.1275 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23940225 PubMed]
 
 
 
==ddT (Taxotere) {{#subobject:08ad0f|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
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" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[https://academic.oup.com/annonc/article/27/10/1873/2389052 Mavroudis et al. 2016 (HORG CT/07.17)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#HORG_CT.2F07.17|See link]]
 
|[[Complex_multipart_regimens#HORG_CT.2F07.17|See link]]
 
|-
 
|}
 
====Preceding treatment====
 
*[[#ddFEC|ddFEC]] x 4
 
====Chemotherapy====
 
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
 
 
====Supportive medications====
 
*[[: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===
 
# Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; Breast Cancer Investigators of the Hellenic Oncology Research Group (HORG), Athens, Greece. 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://academic.oup.com/annonc/article/27/10/1873/2389052 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27502729 PubMed]
 
 
 
==Docetaxel monotherapy {{#subobject:45c144|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
D: '''<u>D</u>'''ocetaxel
 
<br>T: '''<u>T</u>'''axotere (Docetaxel)
 
<br>dT: '''<u>d</u>'''oce'''<u>T</u>'''axel
 
===Regimen #1, 100 mg/m<sup>2</sup> q3wk x 4 {{#subobject:199d79|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ Sparano et al. 2008 (ECOG E1199)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel_monotherapy_2|Paclitaxel, q3wk dosing]]
 
|style="background-color:#91cf60"|Seems to have superior DFS
 
|-
 
|[[#Paclitaxel_monotherapy_2|Paclitaxel, weekly dosing]]<br> Docetaxel, weekly dosing
 
|Not reported
 
|-
 
|[http://jco.ascopubs.org/content/29/29/3877.long Eiermann et al. 2011 (BCIRG-005)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BCIRG-005|See link]]
 
|[[Complex_multipart_regimens#BCIRG-005|See link]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268553/ Slamon et al. 2011 (BCIRG 006)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BCIRG_006|See link]]
 
|[[Complex_multipart_regimens#BCIRG_006|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. Patients in '''BCIRG 006''' were HER2-positive.''
 
====Preceding treatment====
 
*[[#AC_2|AC]] x 4
 
====Chemotherapy====
 
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 1 hour once on day 1
 
 
 
'''21-day cycle for 4 cycles'''
 
 
 
===Regimen #2, 75 mg/m<sup>2</sup> q3wk {{#subobject:2e0391|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[https://www.nature.com/bjc/journal/v117/n2/full/bjc2017158a.html Mavroudis et al. 2017]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#Mavroudis_et_al._2017|See link]]
 
|[[Complex_multipart_regimens#Mavroudis_et_al._2017|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====
 
*[[#Epirubicin_monotherapy|Epirubicin]] x 4
 
====Chemotherapy====
 
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
 
 
 
'''21-day cycle for 4 cycles'''
 
 
 
===Regimen #3, 100 mg/m<sup>2</sup> q3wk x 3 {{#subobject:bfeef2|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa053028 Joensuu et al. 2006 (FinHer)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer,_HER2-positive#TH_.28Taxotere.29_2|TH (Taxotere)]]<br> [[Breast_cancer,_HER2-positive#VH|VH]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[[#Vinorelbine_monotherapy|Vinorelbine]]
 
|style="background-color:#1a9850"|Superior DDFS
 
|-
 
|[http://jco.ascopubs.org/content/24/36/5664.long Roché et al. 2006 (FNCLCC PACS 01)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#FNCLCC_PACS_01|See link]]
 
|[[Complex_multipart_regimens#FNCLCC_PACS_01|See link]]
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2017.72.3494 Ejlertsen et al. 2017 (DBCG 07-READ)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#DBCG_07-READ|See link]]
 
|[[Complex_multipart_regimens#DBCG_07-READ|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. Patients in '''FinHer''' without HER2/neu amplification were only randomized to this or the [[#Vinorelbine_monotherapy|vinorelbine arm]]. Patients in '''DBCG 07-READ''' were TOP2A normal as determined by FISH.''
 
====Preceding treatment====
 
*'''FinHer:''' Breast surgery with axillary lymph node dissection or sentinel lymph node biopsy, within 12 weeks
 
*'''FNCLCC PACS 01:''' [[#FEC_2|FEC]] x 3
 
*'''DBCG 07-READ:''' [[#EC_2|EC]] x 3
 
====Chemotherapy====
 
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 1 hour once on day 1
 
 
 
'''21-day cycle for 3 cycles'''
 
====Subsequent treatment====
 
*'''FinHer:''' [[#FEC_2|FEC]]
 
 
 
===Regimen #4, 35 mg/m<sup>2</sup> weekly {{#subobject:199d79|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ Sparano et al. 2008 (ECOG E1199)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel_monotherapy_2|Paclitaxel, q3wk dosing]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[[#Paclitaxel_monotherapy_2|Paclitaxel, weekly dosing]]<br> Docetaxel, q3wk dosing
 
|Not reported
 
|-
 
|}
 
''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====
 
*[[#AC_2|AC]] x 4
 
====Chemotherapy====
 
*[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV over 1 hour once per week
 
 
 
'''12-week course'''
 
 
 
===References===
 
<!-- no pre-pub disclosed -->
 
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa053028 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16495393 PubMed]
 
## '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2008.21.4577 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19884557 PubMed]
 
<!-- Presented in oral format at the 27th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-11, 2004. -->
 
# 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. [http://jco.ascopubs.org/content/24/36/5664.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17116941 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. -->
 
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa0707056 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18420499 PubMed]
 
## '''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. [http://jco.ascopubs.org/content/33/21/2353.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500829/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26077235 PubMed]
 
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60740-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687939/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19447249 PubMed]
 
<!-- 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. -->
 
# Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martin 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. [http://jco.ascopubs.org/content/29/29/3877.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21911726 PubMed]
 
<!-- no pre-pub disclosed -->
 
# Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. [http://www.nejm.org/doi/full/10.1056/NEJMoa0910383 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268553/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21991949 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.30421/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28081304 PubMed]
 
# 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. 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://www.nature.com/bjc/journal/v117/n2/full/bjc2017158a.html link to original article]'''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28641315 PubMed]
 
# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.3494 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28661759 PubMed]
 
 
 
==EC {{#subobject:8d8dbe|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
EC: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide
 
===Regimen #1, 90/600 x 4 {{#subobject:22ed5f|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30319-4/fulltext Earl et al. 2017 (tAnGo)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|-
 
|}
 
====Preceding treatment====
 
*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====
 
*[[#Paclitaxel_monotherapy_2|Paclitaxel]] versus TG
 
 
 
===Regimen #2, 90/600 x 3 {{#subobject:8d62d4|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2017.72.3494 Ejlertsen et al. 2017 (DBCG 07-READ)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#DBCG_07-READ|See link]]
 
|[[Complex_multipart_regimens#DBCG_07-READ|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. Patients were TOP2A normal as determined by FISH.''
 
====Preceding treatment====
 
*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 3 cycles'''
 
====Subsequent treatment====
 
*[[#Docetaxel_monotherapy_2|Docetaxel]]
 
 
 
===Regimen #3, with range {{#subobject:ef0b86|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|-
 
|}
 
''Patients in '''APHINITY''' had HER2-positive breast cancer. Note that ranges for EC are given in the protocol, replicated here.''
 
====Preceding treatment====
 
*Surgery
 
====Chemotherapy====
 
*[[Epirubicin (Ellence)]] 90 to 120 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 4 cycles'''
 
====Subsequent treatment====
 
*[[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH (Taxol)]] versus [[Breast_cancer,_HER2-positive#THP_.28Taxol.29_2|THP (Taxol)]] or [[Breast_cancer,_HER2-positive#TH_.28Taxotere.29_2|TH (Taxotere)]] versus [[Breast_cancer,_HER2-positive#THP_.28Taxotere.29_2|THP (Taxotere)]]
 
 
 
===Regimen #4, 100/830 {{#subobject:aead26|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/19/12/3103.long Piccart et al. 2001]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#CMF|CMF]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Moderate-dose EC
 
|style="background-color:#91cf60"|Seems to have superior OS
 
|-
 
|}
 
====Preceding treatment====
 
*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 #5, 60/500 {{#subobject:50bd25|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/19/12/3103.long Piccart et al. 2001]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#CMF|CMF]]
 
|Not reported
 
|-
 
|High-dose EC
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|}
 
====Preceding treatment====
 
*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'''
 
 
 
===References===
 
# 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. [http://jco.ascopubs.org/content/19/12/3103.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408507 PubMed]
 
# 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 (GIM) investigators. 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62048-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25740286 PubMed]
 
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30319-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28479233 PubMed]
 
# von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [http://www.nejm.org/doi/full/10.1056/NEJMoa1703643 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''contains verified protocol in supplementary protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28581356 PubMed]
 
# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.3494 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28661759 PubMed]
 
 
 
==Epirubicin monotherapy {{#subobject:fda4d3|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen #1, 100 mg/m<sup>2</sup> {{#subobject:f04a3c|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052084 Poole et al. 2006 (NEAT/BR9601)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BR9601|See link]]
 
|[[Complex_multipart_regimens#BR9601|See link]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489700/ Cameron et al. 2017 (TACT2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#TACT2|See link]]
 
|[[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====
 
*Complete surgical excision
 
====Chemotherapy====
 
*[[Epirubicin (Ellence)]] 100 mg/m<sup>2</sup> IV once on day 1
 
 
 
'''21-day cycle for 4 cycles'''
 
====Subsequent treatment====
 
*'''NEAT''' and '''BR9601:''' [[#CMF|CMF]]
 
*'''TACT2:''' [[#Capecitabine_monotherapy|capecitabine]] versus [[#CMF|CMF]]
 
 
 
===Regimen #2, 90 mg/m<sup>2</sup> {{#subobject:237268|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[https://www.nature.com/bjc/journal/v117/n2/full/bjc2017158a.html Mavroudis et al. 2017]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#Mavroudis_et_al._2017|See link]]
 
|[[Complex_multipart_regimens#Mavroudis_et_al._2017|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
 
====Chemotherapy====
 
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV over 5 to 15 minutes once on day 1
 
 
 
'''21-day cycle for 4 cycles'''
 
====Subsequent treatment====
 
*[[#Docetaxel_monotherapy_2|Docetaxel]]
 
 
 
===References===
 
<!-- no pre-pub disclosed -->
 
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa052084 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17079759 PubMed]
 
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60740-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687939/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19447249 PubMed]
 
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30404-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489700/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28600210 PubMed]
 
# 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. 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://www.nature.com/bjc/journal/v117/n2/full/bjc2017158a.html link to original article]'''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28641315 PubMed]
 
 
 
==FAC {{#subobject:1e6621|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
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 #1, 500/50/500 {{#subobject:63e780|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa043681 Martin et al. 2005 (BCIRG 001)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#TAC_.28Taxotere.29|TAC]]
 
|style="background-color:#d73027"|Inferior OS
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa0910320 Martín et al. 2010 (GEICAM 9805)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#TAC_.28Taxotere.29|TAC]]
 
|style="background-color:#d73027"|Inferior DFS
 
|-
 
|[http://jco.ascopubs.org/content/31/20/2593.long Martín et al. 2013 (GEICAM/2003-02)]
 
|style="background-color:#1a9850"|Phase III
 
|FAC-wP
 
|style="background-color:#fc8d59"|Seems to have inferior DFS
 
|-
 
|}
 
====Preceding treatment====
 
*Surgery
 
====Chemotherapy====
 
*[[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'''
 
 
 
====Supportive medications====
 
*If patients had febrile neutropenia or infection: [[Ciprofloxacin (Cipro)]] 500 mg PO BID on days 5 to 14 of every cycle
 
*G-CSF not originally routinely administered unless patients had febrile neutropenia:
 
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 4 to 11
 
**OR [[Lenograstim (Granocyte)]] 150 mcg/m<sup>2</sup> SC once per day on days 4 to 11
 
 
 
'''21-day cycle for 6 cycles'''
 
 
 
===Regimen #2 {{#subobject:f18a6a|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/23/33/8313.long Hutchins et al. 2005 (INT-0102)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#CMF|CMF]]
 
|style="background-color:#91cf60"|Seems to have superior OS
 
|-
 
|}
 
====Preceding treatment====
 
*Surgery
 
====Chemotherapy====
 
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
*[[Doxorubicin (Adriamycin)]] 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
 
 
 
'''28-day cycle for 6 cycles'''
 
 
 
''Treatment in
 
 
 
===Regimen #3 {{#subobject:53e7a0|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
|[http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19840201)53:3%3C384::AID-CNCR2820530303%3E3.0.CO;2-G/abstract Buzdar et al. 1984]
+
|[https://doi.org/10.1056/nejmoa2202170 Forde et al. 2022 (CheckMate 816)]
|style="background-color:#1a9850"|Phase III
+
|2017-2019
|FAC + BCG
+
| style="background-color:#1a9851" |Phase 3 (C)
|style="background-color:#ffffbf"|Seems not superior
+
|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:#d73027" |Inferior EFS
 
|-
 
|-
 
|}
 
|}
====Preceding treatment====
+
''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.''
*Surgery
+
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*CheckMate 816: No sensitizing EGFR or ALK mutations
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV once per day on days 1 & 8
+
*[[Carboplatin (Paraplatin)]] AUC 5 or 6 IV once on day 1
*[[Doxorubicin (Adriamycin)]] 40 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
*[[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.'''
 
 
 
''After reaching cumulative maximum doxorubicin, patients would go on to receive maintenance CMF. This is now obsolete.''
 
 
 
===Regimen #4, with range {{#subobject:67eda7|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|-
 
|}
 
''Patients in '''APHINITY''' had HER2-positive breast cancer. Note that ranges for FAC are given in the protocol, replicated here.''
 
====Preceding treatment====
 
*Surgery
 
====Chemotherapy====
 
*[[Fluorouracil (5-FU)]] 500 to 600 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 to 600 mg/m<sup>2</sup> IV once on day 1
 
 
 
 
'''21-day cycle for 3 cycles'''
 
'''21-day cycle for 3 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
*[[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH (Taxol)]] versus [[Breast_cancer,_HER2-positive#THP_.28Taxol.29_2|THP (Taxol)]] or [[Breast_cancer,_HER2-positive#TH_.28Taxotere.29_2|TH (Taxotere)]] versus [[Breast_cancer,_HER2-positive#THP_.28Taxotere.29_2|THP (Taxotere)]]
+
*[[Surgery#Surgical_resection|Complete resection]]
 
+
</div></div>
===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-Guerin and with or without irradiation in operable breast cancer. A prospective randomized trial. Cancer. 1984 Feb 1;53(3):384-9. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19840201)53:3%3C384::AID-CNCR2820530303%3E3.0.CO;2-G/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/2705401 PubMed]
 
<!-- no pre-pub disclosed -->
 
# Martin 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 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13. [http://www.nejm.org/doi/full/10.1056/NEJMoa043681 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15930421 PubMed]
 
## '''Update:''' Mackey JR, Martin 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70525-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23246022 PubMed]
 
# 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. [http://jco.ascopubs.org/content/23/33/8313.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16293862 PubMed]
 
<!-- no pre-pub disclosed -->
 
# 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 9805 Investigators. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med. 2010 Dec 2;363(23):2200-10. [http://www.nejm.org/doi/full/10.1056/NEJMoa0910320 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21121833 PubMed]
 
<!-- Presented in part at the 48th Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2012, Chicago, IL. -->
 
# 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. [http://jco.ascopubs.org/content/31/20/2593.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23733779 PubMed]
 
# von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [http://www.nejm.org/doi/full/10.1056/NEJMoa1703643 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''contains verified protocol in supplementary protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28581356 PubMed]
 
 
 
==FEC {{#subobject:3613b7|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
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 #1, 600/60/600 x 6 {{#subobject:d13a49|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://link.springer.com/article/10.1007%2Fs10549-015-3655-1 del Mastro et al. 2016 (GONO-MIG5)]
 
|style="background-color:#1a9850"|Phase III
 
|EP x 4
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Preceding treatment====
 
*Surgery
 
====Chemotherapy====
 
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
*[[Epirubicin (Ellence)]] 60 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 #2, 600/90/600 x 4 {{#subobject:9794f0|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jnci.oxfordjournals.org/content/100/11/805.long Martín et al. 2008 (GEICAM 9906)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#GEICAM_9906|See link]]
 
|[[Complex_multipart_regimens#GEICAM_9906|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
 
====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 4 cycles'''
 
 
 
''Treatment followed by 3 weeks of no treatment, then [[#Paclitaxel_monotherapy_2|paclitaxel]].''
 
 
 
===Regimen #3, 600/90/600 x 6 {{#subobject:916209|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jnci.oxfordjournals.org/content/100/11/805.long Martín et al. 2008 (GEICAM 9906)]
 
|style="background-color:#1a9850"|Phase III
 
|FEC x 4, then [[#Paclitaxel_monotherapy_2|P]]
 
|style="background-color:#d73027"|Inferior DFS
 
|-
 
|}
 
====Preceding treatment====
 
*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 #4, 500/100/500 x 3 {{#subobject:99d167|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/24/36/5664.long Roché et al. 2006 (FNCLCC PACS 01)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#FNCLCC_PACS_01|See link]]
 
|[[Complex_multipart_regimens#FNCLCC_PACS_01|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
 
====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 3 cycles'''
 
====Subsequent treatment====
 
*[[#Docetaxel_monotherapy_2|Docetaxel]]
 
 
 
===Regimen #5, 500/100/500 x 6 {{#subobject:8382ec|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/24/36/5664.long Roché et al. 2006 (FNCLCC PACS 01)]
 
|style="background-color:#1a9850"|Phase III
 
|FEC-[[#Docetaxel_monotherapy_2|D]]
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|}
 
====Preceding treatment====
 
*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 #6, oral cyclophosphamide {{#subobject:978850|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/16/8/2651.long Levine et al. 1998 (NCIC CTG MA5)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#CMF|CMF]]
 
|style="background-color:#1a9850"|Superior RFS
 
|-
 
|[http://annonc.oxfordjournals.org/content/16/5/726.long Coombes et al. 2005 (ICCG HDT trial)]
 
|style="background-color:#1a9850"|Phase III
 
|FEC x 3, then HDT
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Preceding treatment====
 
*Surgery
 
====Chemotherapy====
 
*[[Cyclophosphamide (Cytoxan)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
*[[Epirubicin (Ellence)]] 60 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 #7, 600/60/600 x 3 {{#subobject:e6b54b|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa053028 Joensuu et al. 2006 (FinHer)]
 
|style="background-color:#91cf60"|Non-randomized portion of 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====
 
*'''HER2-negative:''' [[#Docetaxel_monotherapy_2|Docetaxel]] x 3 versus [[#Vinorelbine_monotherapy|vinorelbine]] x 3
 
*'''HER2-positive:''' [[#Docetaxel_monotherapy_2|Docetaxel]] x 3 versus [[Breast_cancer,_HER2-positive#TH_.28Taxotere.29_2|TH]] x 3 versus [[#Vinorelbine_monotherapy|vinorelbine]] x 3 versus [[Breast_cancer,_HER2-positive#VH|VH]] x 3
 
====Chemotherapy====
 
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
*[[Epirubicin (Ellence)]] 60 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 3 cycles'''
 
 
 
===References===
 
# 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. 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. The International Collaborative Cancer Group. J Clin Oncol. 1996 Jan;14(1):35-45. [http://ascopubs.org/doi/full/10.1200/JCO.1996.14.1.35 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8558217 PubMed]
 
# 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. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1998 Aug;16(8):2651-8. [http://jco.ascopubs.org/content/16/8/2651.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://ascopubs.org/doi/full/10.1200/JCO.2005.09.423 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16051958 PubMed]
 
# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2001.19.3.602 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://ascopubs.org/doi/full/10.1200/JCO.2005.05.059 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15837983 PubMed]
 
# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2003.04.148 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12525522 PubMed]
 
# 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. [http://annonc.oxfordjournals.org/content/16/5/726.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15817602 PubMed]
 
<!-- no pre-pub disclosed -->
 
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa053028 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16495393 PubMed]
 
## '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2008.21.4577 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19884557 PubMed]
 
<!-- Presented in oral format at the 27th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-11, 2004. -->
 
# 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. [http://jco.ascopubs.org/content/24/36/5664.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17116941 PubMed]
 
# 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. [http://www.ejcancer.com/article/S0959-8049(07)00014-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17306974 PubMed]
 
# 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 9906 Study Investigators. 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18505968 PubMed]
 
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60740-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687939/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19447249 PubMed]
 
# 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 (GIM) investigators. 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62048-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25740286 PubMed]
 
# 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%2Fs10549-015-3655-1 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26661403 PubMed]
 
# 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. [http://www.ejcancer.com/article/S0959-8049(16)00156-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27125966 PubMed]
 
# 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. [http://www.ejcancer.com/article/S0959-8049(17)30822-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28501763 PubMed]
 
# von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [http://www.nejm.org/doi/full/10.1056/NEJMoa1703643 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''contains verified protocol in supplementary protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28581356 PubMed]
 
 
 
==Paclitaxel monotherapy {{#subobject:5218a|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
T: '''<u>T</u>'''axol (Paclitaxel)
 
<br>pT: '''<u>p</u>'''acli'''<u>T</u>'''axel
 
===Regimen #1, 80 mg/m<sup>2</sup> weekly {{#subobject:6b14dd|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052122 Romond et al. 2005 (NSABP B-31)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH]]
 
|style="background-color:#d73027"|Inferior OS
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052122 Romond et al. 2005 (NCCTG N9831)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#NCCTG_N9831|See link]]
 
|[[Complex_multipart_regimens#NCCTG_N9831|See link]]
 
|-
 
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ Sparano et al. 2008 (ECOG E1199)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|Paclitaxel q3wk
 
|style="background-color:#1a9850"|Superior OS
 
|-
 
|[[#Docetaxel_monotherapy_2|Docetaxel q3wk]]<br> [[#Docetaxel_monotherapy_2|Docetaxel weekly]]
 
|Not reported
 
|-
 
|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ Shulman et al. 2012 (CALGB 40101)]
 
|rowspan=3 style="background-color:#1a9850"|Phase III
 
|[[#ddAC_2|ddAC]] x 4
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|ddAC x 6
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Weekly paclitaxel x 18
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
''Patients in '''NSABP B-31''' and '''NCCTG N9831''' were HER2-positive. This paclitaxel dosing schedule was an option after 2003 in '''NSABP B-31''', and was used for all patients in '''NCCTG N9831'''. In '''CALGB 40101''', this is the dosing before a mid-protocol amendment in 2003.''
 
====Preceding treatment====
 
*[[#AC_2|AC]] x 4
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 1 hour once per week
 
 
 
'''12-week course'''
 
 
 
===Regimen #2, 100 mg/m<sup>2</sup> weekly {{#subobject:d9efe7|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jnci.oxfordjournals.org/content/100/11/805.long Martín et al. 2008 (GEICAM 9906)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#GEICAM_9906|See link]]
 
|[[Complex_multipart_regimens#GEICAM_9906|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====
 
*[[#FEC_2|FEC]] x 4
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 100 mg/m<sup>2</sup> IV once per week
 
 
 
'''8 week course'''
 
 
 
===Regimen #3, 175 mg/m<sup>2</sup> q3wk {{#subobject:c084f5|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/21/6/976.long Henderson et al. 2003 (INT 0148/CALGB 9344)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer_-_obsolete#Observation|Observation]]
 
|style="background-color:#1a9850"|Superior OS
 
|-
 
|[http://jco.ascopubs.org/content/21/8/1431.long Citron et al. 2003 (CALGB 9741)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|
 
|
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052122 Romond et al. 2005 (NSABP B-31)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH]]
 
|style="background-color:#d73027"|Inferior OS
 
|-
 
|rowspan=3|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ Sparano et al. 2008 (ECOG E1199)]
 
|rowspan=3 style="background-color:#1a9850"|Phase III
 
|Paclitaxel weekly
 
|style="background-color:#d73027"|Inferior OS
 
|-
 
|[[#Docetaxel_monotherapy_2|Docetaxel q3wk]]
 
|style="background-color:#fc8d59"|Seems to have inferior DFS
 
|-
 
|[[#Docetaxel_monotherapy_2|Docetaxel weekly]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30319-4/fulltext Earl et al. 2017 (tAnGo)]
 
|style="background-color:#1a9850"|Phase III
 
|TG
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
''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 '''NSABP B-31''' were HER2-positive.''
 
====Preceding treatment====
 
*'''INT 0148/CALGB 9344:''' [[#AC_2|AC]] x 4 versus high-dose AC x 4 versus very-high-dose AC x 4
 
*'''CALGB 9741''', '''NSABP B-31''', and '''ECOG E1199:''' [[#AC_2|AC]] x 4
 
*'''tAnGo:''' [[#EC_2|EC]] x 4
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
 
 
'''21-day cycle for 4 cycles'''
 
 
 
===Regimen #4, 225 mg/m<sup>2</sup> q3wk {{#subobject:b7a984|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/23/16/3686.long Mamounas et al. 2005 (NSABP B-28)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer_-_obsolete#Observation|Observation]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
''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====
 
*[[#AC_2|AC]] x 4
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 225 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
 
 
'''21-day cycle for 4 cycles'''
 
====Subsequent treatment====
 
*'''NCCTG N9831:''' [[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy|H]]
 
===References===
 
# 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. [http://jco.ascopubs.org/content/21/6/976.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12637460 PubMed]
 
# 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. [http://jco.ascopubs.org/content/21/8/1431.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12668651 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. -->
 
# 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. [http://jco.ascopubs.org/content/23/16/3686.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15897552 PubMed]
 
<!-- no pre-pub disclosed -->
 
# Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. [http://www.nejm.org/doi/full/10.1056/NEJMoa052122 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16236738 PubMed]
 
## '''Update:''' Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4491-7. Epub 2011 Oct 31. [http://ascopubs.org/doi/full/10.1200/JCO.2011.36.7045 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236650/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22042958 PubMed]
 
## '''Update:''' Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. [http://ascopubs.org/doi/full/10.1200/JCO.2014.55.5730 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226805/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25332249 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. -->
 
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa0707056 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18420499 PubMed]
 
## '''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. [http://jco.ascopubs.org/content/33/21/2353.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500829/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26077235 PubMed]
 
# 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 9906 Study Investigators. 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18505968 PubMed]
 
# 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. [http://jco.ascopubs.org/content/30/33/4071.long link to original article] '''contains verified protocol''' [http://jco.ascopubs.org/content/suppl/2012/07/23/JCO.2011.40.6405.DC1/Protocol.pdf link to study protocol PDF] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22826271 PubMed]
 
## '''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://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105484/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24934787 PubMed]
 
# 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 (GIM) investigators. 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62048-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25740286 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.30421/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28081304 PubMed]
 
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30319-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28479233 PubMed]
 
 
 
==TAC (Taxotere) {{#subobject:ed77a6|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
TAC: '''<u>T</u>'''axotere (Docetaxel), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
 
 
 
===Regimen {{#subobject:9660e9|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa043681 Martin et al. 2005 (BCIRG 001)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#FAC|FAC]]
 
|style="background-color:#1a9850"|Superior OS
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa0910320 Martín et al. 2010 (GEICAM 9805)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#FAC|FAC]]
 
|style="background-color:#1a9850"|Superior DFS
 
|-
 
|[http://jco.ascopubs.org/content/29/29/3877.long Eiermann et al. 2011 (BCIRG-005)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#AC_2|AC]], then [[#Docetaxel_monotherapy_2|T]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ Swain et al. 2013 (NSABP B-38)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#ddAC_2|ddAC]], then [[#ddT_.28Taxol.29|ddP]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[[#ddAC_2|ddAC]], then ddPG
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ Blum et al. 2017 (USOR 06-090; NSABP-46-I/USOR 07132; NSABP B-49)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#TC_.28Taxotere.29|TC]]
 
|style="background-color:#91cf60"|Seems to have superior 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
 
====Chemotherapy====
 
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1, '''administered third, one hour after cyclophosphamide'''
 
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV over 15 minutes once on day 1, '''administered first'''
 
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV over 1 to 5 minutes once on day 1, '''administered second'''
 
 
 
====Supportive medications====
 
*[[Dexamethasone (Decadron)]] 8 mg PO every 12 hours x 6 total doses, starting the day before treatment
 
*[[Ciprofloxacin (Cipro)]] 500 mg PO BID on days 5 to 14 of every cycle (prophylaxis)
 
*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 -->
 
# Martin 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 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13. [http://www.nejm.org/doi/full/10.1056/NEJMoa043681 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15930421 PubMed]
 
## '''Update:''' Mackey JR, Martin 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70525-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23246022 PubMed]
 
<!-- no pre-pub disclosed -->
 
# 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 9805 Investigators. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med. 2010 Dec 2;363(23):2200-10. [http://www.nejm.org/doi/full/10.1056/NEJMoa0910320 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21121833 PubMed]
 
<!-- 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. -->
 
# Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martin 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. [http://jco.ascopubs.org/content/29/29/3877.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21911726 PubMed]
 
# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2012.48.1275 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757290/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23940225 PubMed]
 
# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.71.4147 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28398846 PubMed]
 
 
 
==TC (Taxotere) {{#subobject:2d2f0e|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
TC: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''yclophosphamide
 
 
 
===Regimen #1, 4 cycles {{#subobject:e9499f|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/24/34/5381.full Jones et al. 2006 (US Oncology Trial 9735)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#AC_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; NSABP-46-I/USOR 07132; NSABP B-49)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#TAC_.28Taxotere.29|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
 
====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 medications====
 
*All cycles given with [[Filgrastim (Neupogen)]] support
 
 
 
'''21-day cycle for 4 cycles'''
 
 
 
===Regimen #2, 6 cycles {{#subobject:d321b7|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[https://academic.oup.com/annonc/article/27/10/1873/2389052 Mavroudis et al. 2016 (HORG CT/07.17)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#ddFEC|ddFEC]], then [[#ddT_.28Taxotere.29|D]]
 
|style="background-color:#ffffbf"|Inconclusive whether non-inferior
 
|-
 
|}
 
====Preceding treatment====
 
*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===
 
# 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. [http://jco.ascopubs.org/content/24/34/5381.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/27/8/1177.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19204201 PubMed]
 
# Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; Breast Cancer Investigators of the Hellenic Oncology Research Group (HORG), Athens, Greece. 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://academic.oup.com/annonc/article/27/10/1873/2389052 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27502729 PubMed]
 
# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.71.4147 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549453/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28398846 PubMed]
 
 
 
==Vinorelbine monotherapy {{#subobject:84c1e0|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
V: '''<u>V</u>'''inorelbine
 
===Regimen {{#subobject:712969|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa053028 Joensuu et al. 2006 (FinHer)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#Docetaxel_monotherapy_2|Docetaxel]]
 
|style="background-color:#d73027"|Inferior DDFS
 
|-
 
|[[Breast_cancer,_HER2-positive#TH_.28Taxotere.29_2|TH (Taxotere)]]<br> [[Breast_cancer,_HER2-positive#VH|VH]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
''Patients without HER2/neu amplification were only randomized to this arm verus the  [[#Docetaxel_monotherapy_2|docetaxel arm]].''
 
====Preceding treatment====
 
*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 -->
 
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa053028 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16495393 PubMed]
 
## '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2008.21.4577 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19884557 PubMed]
 
 
 
=Adjuvant endocrine therapy=
 
==Anastrozole monotherapy {{#subobject:a052f4|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen #1, 5-year course {{#subobject:b05e8a|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2804%2917666-6/fulltext Howell et al. 2005 (ATAC)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|Anastrozole & Tamoxifen
 
|Not reported
 
|-
 
|[[#Tamoxifen_monotherapy|Tamoxifen]]
 
|style="background-color:#91cf60"|Seems to have superior DFS
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612593/ Goss et al. 2013 (NCIC CTG MA.27)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Exemestane_monotherapy|Exemestane]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
 
 
'''5-year course of therapy'''
 
 
 
===Regimen #2, 3-year course {{#subobject:41c2e3|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|style="width: 20%"![[Levels_of_Evidence#Toxicity|Toxicity]]
 
|-
 
|[http://jco.ascopubs.org/content/25/19/2664.long Kaufmann et al. 2007 (ARNO 95)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#ARNO_95|See link]]
 
|[[Complex_multipart_regimens#ARNO_95|See link]]
 
|
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30600-9/fulltext Tjan-Heijnen et al. 2017 (DATA)]
 
|style="background-color:#1a9850"|Phase III
 
|6 y of anastrozole
 
|style="background-color:#fee08b"|Might have inferior DFS
 
|style="background-color:#1a9850"|Less toxic
 
|-
 
|}
 
''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====
 
*'''ARNO 95:''' [[#Tamoxifen_monotherapy|Tamoxifen]] x 2 y
 
*'''DATA:''' [[#Tamoxifen_monotherapy|Tamoxifen]] x 2-3 y
 
====Endocrine therapy====
 
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
 
 
'''3-year course'''
 
 
 
===Regimen #3, 6-year course {{#subobject:ea2190|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|style="width: 20%"![[Levels_of_Evidence#Toxicity|Toxicity]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30600-9/fulltext Tjan-Heijnen et al. 2017 (DATA)]
 
|style="background-color:#1a9850"|Phase III
 
|3 y of anastrozole
 
|style="background-color:#d9ef8b"|Might have superior DFS
 
|style="background-color:#ffffbe"|More toxic
 
|-
 
|}
 
''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====
 
*[[#Tamoxifen_monotherapy|Tamoxifen]] x 2-3 y
 
====Endocrine therapy====
 
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
 
 
'''6-year course'''
 
 
 
===References===
 
# Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS; ATAC Trialists' Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2804%2917666-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15639680 PubMed]
 
## '''Update:''' Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008 Jan;9(1):45-53. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2807%2970385-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18083636 PubMed]
 
## '''Update:''' Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF; ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010 Dec;11(12):1135-41. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70257-6/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21087898 PubMed]
 
<!-- Presented in part in abstract format at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006. -->
 
# Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007 Jul 1;25(19):2664-70. Epub 2007 Jun 11. [http://jco.ascopubs.org/content/25/19/2664.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17563395 PubMed]
 
<!-- Presented at the 33rd Annual San Antonio Breast Cancer Symposium, December 8-12, 2010, San Antonio, TX. -->
 
# Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27--a randomized controlled phase III trial. J Clin Oncol. 2013 Apr 10;31(11):1398-404. Epub 2013 Jan 28. [http://jco.ascopubs.org/content/31/11/1398.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612593/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23358971 PubMed]
 
# Tjan-Heijnen VCG, van Hellemond IEG, Peer PGM, Swinkels ACP, Smorenburg CH, van der Sangen MJC, Kroep JR, De Graaf H, Honkoop AH, Erdkamp FLG, van den Berkmortel FWPJ, de Boer M, de Roos WK, Linn SC, Imholz ALT, Seynaeve CM; Dutch Breast Cancer Research Group (BOOG) for the DATA Investigators. Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1502-1511. Epub 2017 Oct 12. Erratum in: Lancet Oncol. 2017 Nov;18(11):e642. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30600-9/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29031778 PubMed]
 
 
 
==Exemestane monotherapy {{#subobject:62ede3|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
OFS: '''<u>O</u>'''varian '''<u>F</u>'''unction '''<u>S</u>'''uppression
 
 
 
===Regimen #1, with OFS {{#subobject:818d9f|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ Pagani et al. 2014 (TEXT/SOFT)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#Tamoxifen_monotherapy|Tamoxifen]]
 
|style="background-color:#1a9850"|Superior DFS
 
|-
 
|[[#Tamoxifen_monotherapy|Tamoxifen & OFS]]
 
|style="background-color:#1a9850"|Superior DFS
 
|-
 
|}
 
''These regimens are intended for premenopausal patients. '''Pagani et al. 2014''' report on two trials, but only '''SOFT''' had the tamoxifen only arm.''
 
====Endocrine therapy====
 
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
*Ovarian Suppression as follows:
 
**'''TEXT''': [[Triptorelin (Trelstar LA)]] 3.75 mg IM every 28 days
 
***"Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin."
 
**'''SOFT''': Choice of mechanism left to investigators
 
 
 
'''5 years of therapy'''
 
 
 
===Regimen #2, no OFS {{#subobject:31f118|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/26/12/1965.long Mamounas et al. 2008 (NSABP B-33)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Placebo|Placebo]]
 
|style="background-color:#1a9850"|Superior RFS
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612593/ Goss et al. 2013 (NCIC CTG MA.27)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Anastrozole_monotherapy|Anastrozole]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Preceding treatment====
 
*'''NSABP B-33:''' [[Tamoxifen_monotherapy|Tamoxifen]] x 5y
 
====Endocrine therapy====
 
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
 
 
'''5-year course of therapy'''
 
 
 
===Regimen #3, 2 to 3-year course {{#subobject:12d72f|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa040331 Coombes et al. 2004 (Intergroup Exemestane Study)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#Intergroup_Exemestane_Study|See link]]
 
|[[Complex_multipart_regimens#Intergroup_Exemestane_Study|See link]]
 
|-
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62312-4/fulltext van de Velde et al. 2011 (TEAM)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#TEAM|See link]]
 
|[[Complex_multipart_regimens#TEAM|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. The '''Intergroup Exemestane Study''' gave a range of 2 to 3 years of therapy. '''TEAM''' gave a range of 2 to 2.5 years of therapy.''
 
====Preceding treatment====
 
*[[Tamoxifen_monotherapy|Tamoxifen]] x 2-3y
 
====Endocrine therapy====
 
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
 
 
'''2 to 3 years to complete a 5-year course'''
 
 
 
===References===
 
# Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92. [http://www.nejm.org/doi/full/10.1056/NEJMoa040331 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15014181 PubMed]
 
## '''Update:''' Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM; Intergroup Exemestane Study. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2807%2960200-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17307102 PubMed]
 
<!-- Presented in part in abstract format in the Breast Cancer Research Treatment 100:S22, 2006 (suppl; abstr A40). -->
 
# Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1965.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332472 PubMed]
 
# van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011 Jan 22;377(9762):321-31. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62312-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21247627 PubMed]
 
## '''Update:''' Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ, Putter H, Kroep JR, Rea D, Hasenburg A, Markopoulos C, Paridaens R, Smeets JBE, Dirix LY, van de Velde CJH. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1211-1220. Epub 2017 Jul 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30419-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28732650 PubMed]
 
<!-- Presented at the 33rd Annual San Antonio Breast Cancer Symposium, December 8-12, 2010, San Antonio, TX. -->
 
# Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27--a randomized controlled phase III trial. J Clin Oncol. 2013 Apr 10;31(11):1398-404. Epub 2013 Jan 28. [http://jco.ascopubs.org/content/31/11/1398.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612593/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23358971 PubMed]
 
# Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. Epub 2014 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1404037 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24881463 PubMed]
 
 
 
==Letrozole monotherapy {{#subobject:55e6f9|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen #1, 5 years of therapy {{#subobject:adcf9a|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa032312 Goss et al. 2003 (NCIC CTG MA.17)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Placebo|Placebo]]
 
|style="background-color:#1a9850"|Superior DFS
 
|-
 
|rowspan=3|[http://www.nejm.org/doi/full/10.1056/NEJMoa052258 Breast International Group (BIG) 1-98 Collaborative Group 2006]
 
|rowspan=3 style="background-color:#1a9850"|Phase III
 
|[[#Letrozole_monotherapy|Letrozole]], then [[#Tamoxifen_monotherapy|Tamoxifen]]
 
|style="background-color:#ffffbf"|Seems not superior (*)
 
|-
 
|[[#Tamoxifen_monotherapy|Tamoxifen]]
 
|style="background-color:#1a9850"|Superior OS (*)
 
|-
 
|[[#Tamoxifen_monotherapy|Tamoxifen]], then [[#Letrozole_monotherapy|Letrozole]]
 
|style="background-color:#ffffbf"|Seems not superior (*)
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024713/ Goss et al. 2016 (NCIC CTG MA.17R)]
 
|style="background-color:#1a9850"|Phase III
 
|Letrozole x 10y
 
|style="background-color:#d73027"|Inferior DFS
 
|-
 
|}
 
''Efficacy reported for '''BIG 1-98''' based on the 2011 update.''
 
====Preceding treatment====
 
*'''NCIC CTG MA.17:''' Most patients received 5 years of [[#Tamoxifen_monotherapy|tamoxifen]] therapy prior to starting letrozole
 
*'''NCIC CTG MA.17R:''' Letrozole for 5 years
 
====Endocrine therapy====
 
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
 
 
'''5-year course of therapy'''
 
 
 
===Regimen #2, 10 years of therapy {{#subobject:b467cc|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024713/ Goss et al. 2016 (NCIC CTG MA.17R)]
 
|style="background-color:#1a9850"|Phase III
 
|Letrozole x 5y
 
|style="background-color:#1a9850"|Superior DFS
 
|-
 
|}
 
''Continuation of treatment was started within 2 years of the completion of the first 5 years of treatment.''
 
====Preceding treatment====
 
*Letrozole for 5 years
 
====Endocrine therapy====
 
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
 
 
'''5 additional years for a total 10-year course of therapy'''
 
 
 
===Regimen #3, 2 years of therapy {{#subobject:3d1f97|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052258 Breast International Group (BIG) 1-98 Collaborative Group 2006]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BIG_1-98|See link]]
 
|[[Complex_multipart_regimens#BIG_1-98|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.''
 
====Endocrine therapy====
 
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
 
 
'''2-year course'''
 
 
 
''Treatment followed by [[#Tamoxifen_monotherapy|tamoxifen]].''
 
 
 
===Regimen #4, 3 years of therapy {{#subobject:3c3390|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052258 Breast International Group (BIG) 1-98 Collaborative Group 2006]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BIG_1-98|See link]]
 
|[[Complex_multipart_regimens#BIG_1-98|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====
 
*[[#Tamoxifen_monotherapy|Tamoxifen]] x 2y
 
====Endocrine therapy====
 
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
 
 
'''3-year course'''
 
 
 
===References===
 
# Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003 Nov 6;349(19):1793-802. Epub 2003 Oct 9. [http://www.nejm.org/doi/full/10.1056/NEJMoa032312 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14551341 PubMed]
 
## '''Update:''' Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005 Sep 7;97(17):1262-71. [http://jnci.oxfordjournals.org/content/97/17/1262.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16145047 PubMed]
 
## '''Update:''' Muss HB, Tu D, Ingle JN, Martino S, Robert NJ, Pater JL, Whelan TJ, Palmer MJ, Piccart MJ, Shepherd LE, Pritchard KI, He Z, Goss PE. Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG intergroup trial MA.17. J Clin Oncol. 2008 Apr 20;26(12):1956-64. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1956.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332474 PubMed]
 
## '''Subgroup analysis:''' Goss PE, Ingle JN, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Tu D. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008 Apr 20;26(12):1948-55. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1948.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332475 PubMed]
 
## '''Update:''' Jin H, Tu D, Zhao N, Shepherd LE, Goss PE. Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol. 2012 Mar 1;30(7):718-21. Epub 2011 Oct 31. [http://jco.ascopubs.org/content/30/7/718.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295549/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22042967 PubMed]
 
# Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. Wardly, Andrew [corrected to Wardley, Andrew ]. [http://www.nejm.org/doi/full/10.1056/NEJMoa052258 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16382061 PubMed]
 
## '''Update:''' Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007 Feb 10;25(5):486-92. Epub 2007 Jan 2. [http://jco.ascopubs.org/content/25/5/486.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17200148 PubMed]
 
## '''Subgroup analysis:''' Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell'Orto P, Del Curto B, Henriksen KL, Mastropasqua MG, Price KN, Méry E, Lacroix-Triki M, Braye S, Altermatt HJ, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Gusterson BA, Thürlimann B, Coates AS, Viale G; BIG 1-98 Collaborative and International Breast Cancer Study Groups. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol. 2008 Jan;9(1):23-8. Epub 2007 Dec 20. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2807%2970386-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18083065 PubMed]
 
## '''Subgroup analysis:''' Crivellari D, Sun Z, Coates AS, Price KN, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens RJ, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Gladieff L, Rabaglio M, Smith IE, Chirgwin JH, Goldhirsch A. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial. J Clin Oncol. 2008 Apr 20;26(12):1972-9. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1972.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332471 PubMed]
 
## '''Update:''' Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B; BIG 1-98 Collaborative Group; International Breast Cancer Study Group (IBCSG). Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011 Nov;12(12):1101-8. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70270-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235950/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22018631 PubMed]
 
# Zdenkowski N, Forbes JF, Boyle FM, Kannourakis G, Gill PG, Bayliss E, Saunders C, Della-Fiorentina S, Kling N, Campbell I, Mann GB, Coates AS, Gebski V, Davies L, Thornton R, Reaby L, Cuzick J, Green M; Australia and New Zealand Breast Cancer Trials Group. Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial. Ann Oncol. 2016 May;27(5):806-12. Epub 2016 Feb 9. [https://academic.oup.com/annonc/article/27/5/806/2769820 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26861603 PubMed]
 
# Goss PE, Ingle JN, Pritchard KI, Robert NJ, Muss H, Gralow J, Gelmon K, Whelan T, Strasser-Weippl K, Rubin S, Sturtz K, Wolff AC, Winer E, Hudis C, Stopeck A, Beck JT, Kaur JS, Whelan K, Tu D, Parulekar WR. Extending aromatase-inhibitor adjuvant therapy to 10 Years. N Engl J Med. 2016 Jul 21;375(3):209-19. Epub 2016 Jun 5. [http://www.nejm.org/doi/full/10.1056/NEJMoa1604700 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024713/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27264120 PubMed]
 
# Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E, Duijm-de Carpentier M, Putter H, van den Bosch J, Maartense E, van Leeuwen-Stok AE, Liefers GJ, Nortier JWR, Rutgers EJT, van de Velde CJH; IDEAL Study Group. Optimal duration of extended adjuvant endocrine therapy for early breast cancer; results of the IDEAL trial (BOOG 2006-05). J Natl Cancer Inst. 2018 Jan 1;110(1). Epub 2017 Aug 23. [https://academic.oup.com/jnci/article-abstract/110/1/djx134/4093022/Optimal-Duration-of-Extended-Adjuvant-Endocrine link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28922787 PubMed]
 
 
 
==Leuprolide monotherapy {{#subobject:714c67|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen {{#subobject:bf0009|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/25/18/2509.long Schmid et al. 2007 (TABLE)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#CMF|CMF]]
 
|style="background-color:#1a9850"|Superior OS
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Leuprolide (Lupron)]] 3-month depot 11.25 mg SC
 
 
 
'''Every 3 months x 2 years'''
 
 
 
===References===
 
<!-- 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. -->
 
# 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. [http://jco.ascopubs.org/content/25/18/2509.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17577027 PubMed]
 
 
 
==Observation==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.ejcancer.com/article/S0959-8049(04)00565-9/fulltext Rydén et al. 2005 (SBII:2pre)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Tamoxifen_monotherapy|Tamoxifen]]
 
|style="background-color:#d73027"|Inferior RFS
 
|-
 
|[http://jco.ascopubs.org/content/23/33/8313.long Hutchins et al. 2005 (INT-0102)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Tamoxifen_monotherapy|Tamoxifen]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
''No further treatment. Used as a comparator arm.''
 
====Preceding treatment====
 
*'''INT-0102:''' [[#FAC|CAF]] x 6 versus [[#CMF|CMF]] x 6
 
 
 
===References===
 
# Rydén L, Jönsson PE, Chebil G, Dufmats M, Fernö M, Jirström K, Källström AC, Landberg G, Stål O, Thorstenson S, Nordenskjöld B; South Swedish Breast Cancer Group; South-East Swedish Breast Cancer Group. Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up. Eur J Cancer. 2005 Jan;41(2):256-64. [http://www.ejcancer.com/article/S0959-8049(04)00565-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15661551 PubMed]
 
## '''Update:''' Ekholm M, Bendahl PO, Fernö M, Nordenskjöld B, Stål O, Rydén L. Two Years of Adjuvant Tamoxifen Provides a Survival Benefit Compared With No Systemic Treatment in Premenopausal Patients With Primary Breast Cancer: Long-Term Follow-Up (> 25 years) of the Phase III SBII:2pre Trial. J Clin Oncol. 2016 Jul 1;34(19):2232-8. Epub 2016 May 9. [http://jco.ascopubs.org/content/34/19/2232.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27161974 PubMed]
 
# 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. [http://jco.ascopubs.org/content/23/33/8313.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16293862 PubMed]
 
# Zdenkowski N, Forbes JF, Boyle FM, Kannourakis G, Gill PG, Bayliss E, Saunders C, Della-Fiorentina S, Kling N, Campbell I, Mann GB, Coates AS, Gebski V, Davies L, Thornton R, Reaby L, Cuzick J, Green M; Australia and New Zealand Breast Cancer Trials Group. Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial. Ann Oncol. 2016 May;27(5):806-12. Epub 2016 Feb 9. [https://academic.oup.com/annonc/article/27/5/806/2769820 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26861603 PubMed]
 
 
 
==Placebo==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/19/4/931.full Fisher et al. 2001 (NSABP B-23)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Tamoxifen_monotherapy|Tamoxifen]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa032312 Goss et al. 2003 (NCIC CTG MA.17)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Letrozole_monotherapy|Letrozole]]
 
|style="background-color:#d73027"|Inferior DFS
 
|-
 
|[http://jco.ascopubs.org/content/26/12/1965.long Mamounas et al. 2008 (NSABP B-33)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Exemestane_monotherapy|Exemestane]]
 
|style="background-color:#d73027"|Inferior RFS
 
|-
 
|}
 
''No active treatment. Used as a comparator arm.''
 
====Preceding treatment====
 
*'''NSABP B-23:''' [[#CMF|CMF]] x 6 versus [[#AC_2|AC]] x 4
 
*'''NCIC CTG MA.17:''' [[#Tamoxifen_monotherapy|Tamoxifen]] x 5y
 
*'''NSABP B-33:''' [[#Tamoxifen_monotherapy|Tamoxifen]] x 5y
 
 
 
===References===
 
# 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. [http://jco.ascopubs.org/content/19/4/931.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11181655 PubMed]
 
# Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003 Nov 6;349(19):1793-802. Epub 2003 Oct 9. [http://www.nejm.org/doi/full/10.1056/NEJMoa032312 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14551341 PubMed]
 
## '''Update:''' Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005 Sep 7;97(17):1262-71. [http://jnci.oxfordjournals.org/content/97/17/1262.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16145047 PubMed]
 
## '''Update:''' Muss HB, Tu D, Ingle JN, Martino S, Robert NJ, Pater JL, Whelan TJ, Palmer MJ, Piccart MJ, Shepherd LE, Pritchard KI, He Z, Goss PE. Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG intergroup trial MA.17. J Clin Oncol. 2008 Apr 20;26(12):1956-64. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1956.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332474 PubMed]
 
## '''Subgroup analysis:''' Goss PE, Ingle JN, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Tu D. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008 Apr 20;26(12):1948-55. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1948.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332475 PubMed]
 
## '''Update:''' Jin H, Tu D, Zhao N, Shepherd LE, Goss PE. Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol. 2012 Mar 1;30(7):718-21. Epub 2011 Oct 31. [http://jco.ascopubs.org/content/30/7/718.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295549/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22042967 PubMed]
 
<!-- Presented in part in abstract format in the Breast Cancer Research Treatment 100:S22, 2006 (suppl; abstr A40). -->
 
# Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1965.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332472 PubMed]
 
 
 
==Tamoxifen monotherapy {{#subobject:2e0ab1|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
OFS: '''<u>O</u>'''varian '''<u>F</u>'''unction '''<u>S</u>'''uppression
 
===Regimen #1, 5 years, no OFS {{#subobject:dc8bc3|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/19/4/931.full Fisher et al. 2001 (NSABP B-23)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Placebo|Placebo]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.11396/full Assikis et al. 2003]
 
|style="background-color:#1a9850"|Phase III
 
|[[#FAC|FAC]], then [[Breast_cancer_-_obsolete#MV|MV]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa040331 Coombes et al. 2004 (Intergroup Exemestane Study)]
 
|style="background-color:#1a9850"|Phase III
 
|Tamoxifen x 2-3y, then [[#Exemestane_monotherapy|Exemestane]] x 2-3y
 
|style="background-color:#fee08b"|Might have inferior OS (*)
 
|-
 
|[http://jco.ascopubs.org/content/23/33/8313.long Hutchins et al. 2005 (INT-0102)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Observation|Observation]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|rowspan=3|[http://www.nejm.org/doi/full/10.1056/NEJMoa052258 Breast International Group (BIG) 1-98 Collaborative Group 2006]
 
|rowspan=3 style="background-color:#1a9850"|Phase III
 
|[[#Letrozole_monotherapy|Letrozole]]
 
|style="background-color:#d73027"|Inferior OS (*)
 
|-
 
|[[#Letrozole_monotherapy|Letrozole]] x 2y, then Tamoxifen x 3y
 
|Not reported
 
|-
 
|Tamoxifen x 2y, then [[#Letrozole_monotherapy|Letrozole]] x 3y
 
|Not reported
 
|-
 
|[http://jco.ascopubs.org/content/25/19/2664.long Kaufmann et al. 2007 (ARNO 95)]
 
|style="background-color:#1a9850"|Phase III
 
|Tamoxifen x 2y, then [[#Anastrozole_monotherapy|Anastrozole]] x 3y
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|[http://jco.ascopubs.org/content/26/12/1965.long Mamounas et al. 2008 (NSABP B-33)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|
 
|
 
|-
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62312-4/fulltext van de Velde et al. 2011 (TEAM)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Tamoxifen_monotherapy|Tamoxifen]] x 2.5-3y, then [[#Exemestane_monotherapy|Exemestane]] x 2-2.5y
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61963-1/abstract Davies et al. 2013 (ATLAS)]
 
|style="background-color:#1a9850"|Phase III
 
|Tamoxifen x 10 years
 
|style="background-color:#d73027"|Inferior OS
 
|-
 
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ Pagani et al. 2014 (SOFT)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#Exemestane_monotherapy|Exemestane & OFS]]
 
|style="background-color:#d73027"|Inferior DFS
 
|-
 
|Tamoxifen & OFS
 
|Not reported
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681581/ Chapman et al. 2015 (NCIC CTG MA.14 & NSABP B-29)]
 
|style="background-color:#1a9850"|Phase III
 
|Tamoxifen & Octreotide LAR
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
''Note: '''Pagani et al. 2014''' report on two trials, but only '''SOFT''' had the tamoxifen only arm. Efficacy for '''BIG 1-98''' is based on the 2011 update.''
 
====Preceding treatment====
 
*'''NSABP B-23:''' [[#CMF|CMF]] x 6 versus [[#AC_2|AC]] x 4
 
*'''INT-0102:''' [[#FAC|CAF]] x 6 versus [[#CMF|CMF]] x 6
 
====Endocrine therapy====
 
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
 
 
'''5 years of therapy'''
 
====Subsequent treatment====
 
*'''NSABP B-33:''' [[#Exemestane_monotherapy|Exemestane]] versus [[#Placebo|Placebo]]
 
 
 
===Regimen #2, 5 years with OFS {{#subobject:ed9421|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ Pagani et al. 2014 (TEXT/SOFT)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#Exemestane_monotherapy|Exemestane & OFS]]
 
|style="background-color:#d73027"|Inferior DFS
 
|-
 
|Tamoxifen
 
|Not reported
 
|-
 
|}
 
''These regimens are intended for premenopausal patients. '''Pagani et al. 2014''' report on two trials, but only '''SOFT''' had the tamoxifen only arm.''
 
====Endocrine therapy====
 
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
*Ovarian Suppression as follows:
 
**'''TEXT''': [[Triptorelin (Trelstar LA)]] 3.75 mg IM every 28 days
 
***"Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin."
 
**'''SOFT''': Choice of mechanism left to investigators
 
 
 
'''5 years of therapy'''
 
 
 
===Regimen #3, 10 years {{#subobject:43a51a|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61963-1/abstract Davies et al. 2013 (ATLAS)]
 
|style="background-color:#1a9850"|Phase III
 
|Tamoxifen x 5 years
 
|style="background-color:#1a9850"|Superior OS
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
 
 
'''10 years of therapy'''
 
 
 
===Regimen #3, 2 years of therapy {{#subobject:bb9926|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa040331 Coombes et al. 2004 (Intergroup Exemestane Study)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#Intergroup_Exemestane_Study|See link]]
 
|[[Complex_multipart_regimens#Intergroup_Exemestane_Study|See link]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052258 Breast International Group (BIG) 1-98 Collaborative Group 2006]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BIG_1-98|See link]]
 
|[[Complex_multipart_regimens#BIG_1-98|See link]]
 
|-
 
|[http://jco.ascopubs.org/content/25/19/2664.long Kaufmann et al. 2007 (ARNO 95)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#ARNO_95|See link]]
 
|[[Complex_multipart_regimens#ARNO_95|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. The '''Intergroup Exemestane Study''' gave a range of 2 to 3 years of therapy.''
 
====Endocrine therapy====
 
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
 
 
'''2-year course'''
 
====Subsequent treatment====
 
*'''Intergroup Exemestane Study:''' [[#Exemestane_monotherapy|Exemestane]]
 
*'''BIG 1-98:''' [[#Letrozole_monotherapy|Letrozole]]
 
*'''ARNO 95:''' [[#Anastrozole_monotherapy|Anastrozole]]
 
 
 
===Regimen #4, 3 years of therapy {{#subobject:7a4c78|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa052258 Breast International Group (BIG) 1-98 Collaborative Group 2006]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#BIG_1-98|See link]]
 
|[[Complex_multipart_regimens#BIG_1-98|See link]]
 
|-
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62312-4/fulltext van de Velde et al. 2011 (TEAM)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#TEAM|See link]]
 
|[[Complex_multipart_regimens#TEAM|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. '''TEAM''' gave a range of 2.5 to 3 years of therapy.''
 
====Preceding treatment====
 
*'''BIG 1-98:''' [[#Letrozole_monotherapy|Letrozole]] x 2y
 
====Endocrine therapy====
 
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
 
 
'''3-year course'''
 
====Subsequent treatment====
 
*'''TEAM:''' [[#Exemestane_monotherapy|Exemestane]]
 
 
 
===Regimen #5, 1 year {{#subobject:97eecb|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://www.ejcancer.com/article/S0959-8049(13)00383-3/fulltext Eljertsen et al. 2013 (DBCG 82C)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#CMFT|CMFT]]
 
|style="background-color:#d73027"|Inferior DFS
 
|-
 
|Tamoxifen & RT
 
|Not reported
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Tamoxifen (Nolvadex)]] 30 mg PO once per day
 
 
 
'''1 year of therapy'''
 
 
 
===References===
 
# '''Review:''' Jaiyesimi IA, Buzdar AU, Decker DA, Hortobagyi GN. Use of tamoxifen for breast cancer: twenty-eight years later. J Clin Oncol. 1995 Feb;13(2):513-29. [http://jco.ascopubs.org/content/13/2/513.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7844613 PubMed]
 
# 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. [http://jco.ascopubs.org/content/19/4/931.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11181655 PubMed]
 
# Assikis V, Buzdar A, Yang Y, Smith T, Theriault R, Booser D, Valero V, Walters R, Singletary E, Ames F, Hortobagyi G. A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003 Jun 1;97(11):2716-23. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.11396/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12767083 PubMed]
 
# Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92. [http://www.nejm.org/doi/full/10.1056/NEJMoa040331 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15014181 PubMed]
 
## '''Update:''' Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM; Intergroup Exemestane Study. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2807%2960200-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17307102 PubMed]
 
# Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS; ATAC Trialists' Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2804%2917666-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15639680 PubMed]
 
## '''Update:''' Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008 Jan;9(1):45-53. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2807%2970385-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18083636 PubMed]
 
## '''Update:''' Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF; ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010 Dec;11(12):1135-41. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70257-6/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21087898 PubMed]
 
# Rydén L, Jönsson PE, Chebil G, Dufmats M, Fernö M, Jirström K, Källström AC, Landberg G, Stål O, Thorstenson S, Nordenskjöld B; South Swedish Breast Cancer Group; South-East Swedish Breast Cancer Group. Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up. Eur J Cancer. 2005 Jan;41(2):256-64. [http://www.ejcancer.com/article/S0959-8049(04)00565-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15661551 PubMed]
 
## '''Update:''' Ekholm M, Bendahl PO, Fernö M, Nordenskjöld B, Stål O, Rydén L. Two years of adjuvant tamoxifen provides a survival benefit compared with no systemic treatment in premenopausal patients with primary breast cancer: Long-term follow-up (> 25 years) of the phase III SBII:2pre trial. J Clin Oncol. 2016 Jul 1;34(19):2232-8. Epub 2016 May 9. [http://jco.ascopubs.org/content/34/19/2232.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27161974 PubMed]
 
# '''Review:''' Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2805%2966544-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15894097 PubMed]
 
# 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. [http://jco.ascopubs.org/content/23/33/8313.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16293862 PubMed]
 
# Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. Wardly, Andrew [corrected to Wardley, Andrew ]. [http://www.nejm.org/doi/full/10.1056/NEJMoa052258 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16382061 PubMed]
 
## '''Update:''' Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007 Feb 10;25(5):486-92. Epub 2007 Jan 2. [http://jco.ascopubs.org/content/25/5/486.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17200148 PubMed]
 
## '''Subgroup analysis:''' Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell'Orto P, Del Curto B, Henriksen KL, Mastropasqua MG, Price KN, Méry E, Lacroix-Triki M, Braye S, Altermatt HJ, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Gusterson BA, Thürlimann B, Coates AS, Viale G; BIG 1-98 Collaborative and International Breast Cancer Study Groups. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol. 2008 Jan;9(1):23-8. Epub 2007 Dec 20. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2807%2970386-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18083065 PubMed]
 
## '''Subgroup analysis:''' Crivellari D, Sun Z, Coates AS, Price KN, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens RJ, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Gladieff L, Rabaglio M, Smith IE, Chirgwin JH, Goldhirsch A. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial. J Clin Oncol. 2008 Apr 20;26(12):1972-9. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1972.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332471 PubMed]
 
## '''Update:''' Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B; BIG 1-98 Collaborative Group.; International Breast Cancer Study Group (IBCSG). Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011 Nov;12(12):1101-8. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70270-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235950/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22018631 PubMed]
 
<!-- Presented in part in abstract format at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006. -->
 
# Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007 Jul 1;25(19):2664-70. Epub 2007 Jun 11. [http://jco.ascopubs.org/content/25/19/2664.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17563395 PubMed]
 
<!-- Presented in part in abstract format in the Breast Cancer Research Treatment 100:S22, 2006 (suppl; abstr A40). -->
 
# Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1965.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332472 PubMed]
 
# van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011 Jan 22;377(9762):321-31. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62312-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21247627 PubMed]
 
## '''Update:''' Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ, Putter H, Kroep JR, Rea D, Hasenburg A, Markopoulos C, Paridaens R, Smeets JBE, Dirix LY, van de Velde CJH. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1211-1220. Epub 2017 Jul 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30419-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28732650 PubMed]
 
# Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, Abraham M, Medeiros Alencar VH, Badran A, Bonfill X, Bradbury J, Clarke M, Collins R, Davis SR, Delmestri A, Forbes JF, Haddad P, Hou MF, Inbar M, Khaled H, Kielanowska J, Kwan WH, Mathew BS, Mittra I, Müller B, Nicolucci A, Peralta O, Pernas F, Petruzelka L, Pienkowski T, Radhika R, Rajan B, Rubach MT, Tort S, Urrútia G, Valentini M, Wang Y, Peto R; Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013 Mar 9;381(9869):805-16. Erratum in: Lancet. 2013 Mar 9;381(9869):804. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61963-1/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596060/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23219286 PubMed]
 
# 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. [http://www.ejcancer.com/article/S0959-8049(13)00383-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23756360 PubMed]
 
# Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. Epub 2014 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1404037 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24881463 PubMed]
 
# Chapman JA, Costantino JP, Dong B, Margolese RG, Pritchard KI, Shepherd LE, Gelmon KA, Wolmark N, Pollak MN. Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC CTG MA.14 and NSABP B-29. Breast Cancer Res Treat. 2015 Sep;153(2):353-60. Epub 2015 Aug 15. [http://link.springer.com/article/10.1007%2Fs10549-015-3547-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681581/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26276354 PubMed]
 
 
 
=Metastatic disease, endocrine therapy=
 
==Abemaciclib & Anastrozole {{#subobject:213a4e|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:c0e636|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2017.75.6155 Goetz et al. 2017 (MONARCH 3)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Anastrozole_monotherapy_2|Anastrozole]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
====Chemotherapy====
 
*[[Abemaciclib (Verzenio)]] 150 mg PO BID
 
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
 
 
'''28-day cycles, continued until progression'''
 
 
 
===References===
 
# Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. [http://ascopubs.org/doi/full/10.1200/JCO.2017.75.6155 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28968163 PubMed]
 
 
 
==Abemaciclib & Fulvestrant {{#subobject:9cf796|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:35ec78|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2017.73.7585 Sledge et al. 2017 (MONARCH 2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Fulvestrant_monotherapy|Fulvestrant]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
====Chemotherapy====
 
*[[Abemaciclib (Verzenio)]] 150 mg PO BID
 
*[[Fulvestrant (Faslodex)]] as follows:
 
**Cycle 1: 500 mg IM once per day on days 1 & 15
 
**Cycle 2 onwards: 500 mg IM once on day 1
 
 
 
'''28-day cycles, continued until progression'''
 
 
 
===References===
 
# Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017 Sep 1;35(25):2875-2884. Epub 2017 Jun 3. [http://ascopubs.org/doi/full/10.1200/JCO.2017.73.7585 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28580882 PubMed]
 
 
 
==Abemaciclib & Letrozole {{#subobject:cb27ef|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:e434e3|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2017.75.6155 Goetz et al. 2017 (MONARCH 3)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Letrozole_monotherapy_2|Letrozole]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
====Chemotherapy====
 
*[[Abemaciclib (Verzenio)]] 150 mg PO BID
 
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
 
 
'''28-day cycles, continued until progression'''
 
 
 
===References===
 
# Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. [http://ascopubs.org/doi/full/10.1200/JCO.2017.75.6155 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28968163 PubMed]
 
 
 
==Anastrozole monotherapy {{#subobject:796bb|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen {{#subobject:bd033c|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
|style="width: 25%"!Study
 
|style="width: 25%"![[Levels_of_Evidence#Evidence|Evidence]]
 
|style="width: 25%"!Comparator
 
|style="width: 25%"![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/20/16/3396.long Howell et al. 2002]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Fulvestrant_monotherapy|Fulvestrant]]
 
|style="background-color:#eeee00"|Seems to have non-inferior TTP
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2011.38.1095 Bergh et al. 2012 (FACT)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Anastrozole_.26_Fulvestrant|Anastrozole & Fulvestrant]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951300/ Mehta et al. 2012 (SWOG S0226)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Anastrozole_.26_Fulvestrant|Anastrozole & Fulvestrant]]
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32389-3/fulltext Robertson et al. 2016 (FALCON)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Fulvestrant_monotherapy|Fulvestrant]]
 
|style="background-color:#fc8d59"|Seems to have inferior PFS
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2017.75.6155 Goetz et al. 2017 (MONARCH 3)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Abemaciclib_.26_Anastrozole|Abemaciclib & Anastrozole]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|[http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 Tripathy et al. 2017 (MONALEESA-7)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Anastrozole_.26_Ribociclib|Anastrozole & Ribociclib]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
====Supportive medications====
 
*For premenopausal patients:
 
**'''MONALEESA-7:''' [[Goserelin (Zoladex)]] 3.8 mg SC once every 28 days
 
 
 
===References===
 
# Howell A, Robertson JF, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol. 2002 Aug 15;20(16):3396-403. [http://jco.ascopubs.org/content/20/16/3396.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12177099 PubMed]
 
# Bergh J, Jönsson PE, Lidbrink EK, Trudeau M, Eiermann W, Brattström D, Lindemann JP, Wiklund F, Henriksson R. FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol. 2012 Jun 1;30(16):1919-25. Epub 2012 Feb 27. [http://ascopubs.org/doi/full/10.1200/JCO.2011.38.1095 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22370325 PubMed]
 
# Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Livingston RB, Hortobagyi GN. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012 Aug 2;367(5):435-44. [http://www.nejm.org/doi/full/10.1056/NEJMoa1201622 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951300/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22853014 PubMed]
 
# Robertson JF, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A, Shparyk Y, Cardona-Huerta S, Cheung KL, Philco-Salas MJ, Ruiz-Borrego M, Shao Z, Noguchi S, Rowbottom J, Stuart M, Grinsted LM, Fazal M, Ellis MJ. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016 Dec 17;388(10063):2997-3005. Epub 2016 Nov 28. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32389-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27908454 PubMed]
 
# Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. [http://ascopubs.org/doi/full/10.1200/JCO.2017.75.6155 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28968163 PubMed]
 
# '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains protocol'''
 
 
 
==Anastrozole & Fulvestrant {{#subobject:c3bc6e|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:7ef8ed|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2011.38.1095 Bergh et al. 2012 (FACT)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Anastrozole_monotherapy_2|Anastrozole]]
 
|style="background-color:#eeee00"|Seems not superior
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951300/ Mehta et al. 2012 (SWOG S0226)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Anastrozole_monotherapy_2|Anastrozole]]
 
|style="background-color:#91cf60"|Seems to have superior OS
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
*[[Fulvestrant (Faslodex)]] 500 mg IM once on day 1, then 250 mg IM once per day on days 14 & 28, then 250 mg IM once every four weeks
 
**Patients in '''SWOG S0226''' who progressed while on therapy were allowed to receive a higher dose, 500 mg IM once every four weeks
 
 
 
'''28-day cycles, given until progression of disease or unacceptable toxicity'''
 
 
 
===References===
 
# Bergh J, Jönsson PE, Lidbrink EK, Trudeau M, Eiermann W, Brattström D, Lindemann JP, Wiklund F, Henriksson R. FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol. 2012 Jun 1;30(16):1919-25. Epub 2012 Feb 27. [http://ascopubs.org/doi/full/10.1200/JCO.2011.38.1095 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22370325 PubMed]
 
# Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Livingston RB, Hortobagyi GN. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012 Aug 2;367(5):435-44. [http://www.nejm.org/doi/full/10.1056/NEJMoa1201622 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951300/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22853014 PubMed]
 
 
 
==Anastrozole & Ribociclib {{#subobject:443971|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:d9afb9|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 Tripathy et al. 2017 (MONALEESA-7)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Anastrozole_monotherapy_2|Anastrozole]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
====Therapy====
 
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
*[[Ribociclib (Kisqali)]] 600 mg PO once per day on days 1 to 21
 
====Supportive medications====
 
*[[Goserelin (Zoladex)]] 3.8 mg SC once every 28 days
 
 
 
'''28-day cycles, given until progression of disease or unacceptable toxicity'''
 
 
 
===References===
 
# '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains protocol'''
 
 
 
==Exemestane monotherapy {{#subobject:a3d882|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen {{#subobject:49119f|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/26/10/1664.long Chia et al. 2008 (EFECT)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Fulvestrant_monotherapy|Fulvestrant]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1109653 Baselga et al. 2012 (BOLERO-2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Exemestane_.26_Everolimus|Everolimus & Exemestane]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
 
 
===References===
 
<!-- Presented in part at the 29th Annual San Antonio Breast Cancer Symposium December 14-17, 2006, San Antonio, Texas. -->
 
# Chia S, Gradishar W, Mauriac L, Bines J, Amant F, Federico M, Fein L, Romieu G, Buzdar A, Robertson JF, Brufsky A, Possinger K, Rennie P, Sapunar F, Lowe E, Piccart M. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol. 2008 Apr 1;26(10):1664-70. Epub 2008 Mar 3. [http://jco.ascopubs.org/content/26/10/1664.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18316794 PubMed]
 
# Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. Epub 2011 Dec 7. [http://www.nejm.org/doi/full/10.1056/NEJMoa1109653 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22149876 PubMed]
 
## '''Update:''' Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. Erratum in: Adv Ther. 2014 Sep;31(9):1008-9. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898123/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24158787 PubMed]
 
 
 
See [[#Exemestane_monotherapy|references for Exemestane (Aromasin)]]
 
 
 
==Exemestane & Everolimus {{#subobject:c6aadc|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:fdbaa3|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1109653 Baselga et al. 2012 (BOLERO-2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Exemestane_monotherapy_2|Exemestane]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
====Therapy====
 
*[[Everolimus (Afinitor)]] 10 mg PO once per day
 
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
 
 
'''Given until progression of disease or unacceptable toxicity'''
 
 
 
===References===
 
# Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. Epub 2011 Dec 7. [http://www.nejm.org/doi/full/10.1056/NEJMoa1109653 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22149876 PubMed]
 
## '''Update:''' Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. Erratum in: Adv Ther. 2014 Sep;31(9):1008-9. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898123/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24158787 PubMed]
 
 
 
==Fulvestrant monotherapy {{#subobject:c91702|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen {{#subobject:bd033c|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/20/16/3396.long Howell et al. 2002]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Anastrozole_monotherapy_2|Anastrozole]]
 
|style="background-color:#eeee00"|Seems to have non-inferior TTP
 
|-
 
|[http://jco.ascopubs.org/content/22/9/1605.long Howell et al. 2004]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Tamoxifen_monotherapy_2|Tamoxifen]]
 
|style="background-color:#fee08b"|Might have inferior TTP
 
|-
 
|[http://jco.ascopubs.org/content/26/10/1664.long Chia et al. 2008 (EFECT)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Exemestane_monotherapy_2|Exemestane]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2010.28.8415 Di Leo et al. 2010 (CONFIRM)]
 
|style="background-color:#1a9850"|Phase III
 
|Fulvestrant 250 mg
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1505270 Turner et al. 2015 (PALOMA-3)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Fulvestrant_.26_Palbociclib|Fulvestrant & Palbociclib]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32389-3/fulltext Robertson et al. 2016 (FALCON)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Anastrozole_monotherapy_2|Anastrozole]]
 
|style="background-color:#91cf60"|Seems to have superior PFS
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549667/ Baselga et al. 2017 (BELLE-2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Buparlisib_(BKM120)|Buparlisib]] & Fulvestrant
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2017.73.7585 Sledge et al. 2017 (MONARCH 2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Fulvestrant_monotherapy|Fulvestrant]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|}
 
''Note: while this regimen was inferior in '''BELLE-2''', the authors note that "no further studies are being pursued because of the toxicity associated with [the experimental arm]."''
 
====Endocrine therapy====
 
*[[Fulvestrant (Faslodex)]] as follows:
 
**Cycle 1: 500 mg IM once per day on days 1 & 15
 
**Cycle 2 onwards: 500 mg IM once on day 1
 
 
 
'''28-day cycles, continued until progression'''
 
 
 
===References===
 
# Howell A, Robertson JF, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol. 2002 Aug 15;20(16):3396-403. [http://jco.ascopubs.org/content/20/16/3396.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12177099 PubMed]
 
# Howell A, Robertson JF, Abram P, Lichinitser MR, Elledge R, Bajetta E, Watanabe T, Morris C, Webster A, Dimery I, Osborne CK. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol. 2004 May 1;22(9):1605-13. [http://jco.ascopubs.org/content/22/9/1605.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15117982 PubMed]
 
# Perey L, Paridaens R, Hawle H, Zaman K, Nolé F, Wildiers H, Fiche M, Dietrich D, Clément P, Köberle D, Goldhirsch A, Thürlimann B. Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00). Ann Oncol. 2007 Jan;18(1):64-9. Epub 2006 Oct 9. [http://annonc.oxfordjournals.org/content/18/1/64.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17030543 PubMed]
 
<!-- Presented in part at the 29th Annual San Antonio Breast Cancer Symposium December 14-17, 2006, San Antonio, Texas. -->
 
# Chia S, Gradishar W, Mauriac L, Bines J, Amant F, Federico M, Fein L, Romieu G, Buzdar A, Robertson JF, Brufsky A, Possinger K, Rennie P, Sapunar F, Lowe E, Piccart M. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol. 2008 Apr 1;26(10):1664-70. Epub 2008 Mar 3. [http://jco.ascopubs.org/content/26/10/1664.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18316794 PubMed]
 
# Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR, Pendergrass K, Garnett S, Lindemann JP, Sapunar F, Martin M. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2010 Oct 20;28(30):4594-600. Epub 2010 Sep 20. Erratum in: J Clin Oncol. 2011 Jun 1;29(16):2293. [http://ascopubs.org/doi/full/10.1200/JCO.2010.28.8415 link to original article][https://www.ncbi.nlm.nih.gov/pubmed/20855825 PubMed]
 
# Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M; PALOMA3 Study Group. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015 Jul 16;373(3):209-19. Epub 2015 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1505270 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26030518 PubMed]
 
## '''Update:''' Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016 Apr;17(4):425-39. Epub 2016 Mar 3. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00613-0/fulltext link to original article][https://www.ncbi.nlm.nih.gov/pubmed/26947331 PubMed]
 
# Robertson JF, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A, Shparyk Y, Cardona-Huerta S, Cheung KL, Philco-Salas MJ, Ruiz-Borrego M, Shao Z, Noguchi S, Rowbottom J, Stuart M, Grinsted LM, Fazal M, Ellis MJ. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016 Dec 17;388(10063):2997-3005. Epub 2016 Nov 28. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32389-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27908454 PubMed]
 
# Baselga J, Im SA, Iwata H, Cortés J, De Laurentiis M, Jiang Z, Arteaga CL, Jonat W, Clemons M, Ito Y, Awada A, Chia S, Jagiełło-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Takahashi M, Vuylsteke P, Hachemi S, Dharan B, Di Tomaso E, Urban P, Massacesi C, Campone M. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):904-916. Epub 2017 May 30. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30376-5/fulltext link to original article][https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549667/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28576675 PubMed]
 
# Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017 Sep 1;35(25):2875-2884. Epub 2017 Jun 3. [http://ascopubs.org/doi/full/10.1200/JCO.2017.73.7585 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28580882 PubMed]
 
 
 
==Fulvestrant & Palbociclib {{#subobject:a59b43|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:f3a761|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1505270 Turner et al. 2015 (PALOMA-3)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Fulvestrant_monotherapy|Fulvestrant]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
====Therapy====
 
*[[Fulvestrant (Faslodex)]] 500 mg IM once every 2 weeks for 3 doses, then once every 4 weeks
 
*[[Palbociclib (Ibrance)]] 125 mg PO once per day on days 1 to 21
 
 
 
'''28-day cycles'''
 
 
 
===References===
 
# Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M; PALOMA3 Study Group. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Jul 16;373(3):209-19. Epub 2015 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1505270 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26030518 PubMed]
 
## '''Update:''' Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016 Apr;17(4):425-39. Epub 2016 Mar 3. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00613-0/fulltext link to original article][https://www.ncbi.nlm.nih.gov/pubmed/26947331 PubMed]
 
 
 
==Letrozole monotherapy {{#subobject:75d541|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen {{#subobject:d7ef99|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2971159-3/abstract Finn et al. 2015 (PALOMA-1/TRIO-18)]
 
|style="background-color:#1a9850"|Randomized Phase II
 
|[[#Letrozole_.26_Palbociclib|Letrozole & Palbociclib]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012690/ Dickler et al. 2016 (CALGB 40503)]
 
|style="background-color:#1a9850"|Phase III
 
|Letrozole & Bevacizumab
 
|style="background-color:#fc8d59"|Seems to have inferior PFS
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1609709 Hortobagyi et al. 2016 (MONALEESA-2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Letrozole_.26_Ribociclib|Letrozole & Ribociclib]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1607303 Finn et al. 2016 (PALOMA-2)]
 
|style="background-color:#1a9850"|Randomized Phase II
 
|[[#Letrozole_.26_Palbociclib|Letrozole & Palbociclib]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2017.75.6155 Goetz et al. 2017 (MONARCH 3)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Abemaciclib_.26_Letrozole|Abemaciclib & Letrozole]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|[http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 Tripathy et al. 2017 (MONALEESA-7)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Letrozole_.26_Ribociclib|Letrozole & Ribociclib]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
====Supportive medications====
 
*For premenopausal patients:
 
**'''MONALEESA-7:''' [[Goserelin (Zoladex)]] 3.8 mg SC once every 28 days
 
 
 
===References===
 
See [[#Letrozole_monotherapy|references for Letrozole (Femara)]]
 
# Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2971159-3/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25524798 PubMed]
 
<!-- Presented in part at the 51st Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 29-June 2, 2015. -->
 
# Dickler MN, Barry WT, Cirrincione CT, Ellis MJ, Moynahan ME, Innocenti F, Hurria A, Rugo HS, Lake DE, Hahn O, Schneider BP, Tripathy D, Carey LA, Winer EP, Hudis CA. Phase III trial evaluating letrozole as first-line endocrine therapy with or without bevacizumab for the treatment of postmenopausal women with hormone receptor-positive advanced-stage breast cancer: CALGB 40503 (Alliance). J Clin Oncol. 2016 Aug 1;34(22):2602-9. Epub 2016 May 2. [http://jco.ascopubs.org/content/34/22/2602.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012690/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27138575 PubMed]
 
# Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O'Shaughnessy J. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016 Nov 3;375(18):1738-1748. Epub 2016 Oct 7.[http://www.nejm.org/doi/full/10.1056/NEJMoa1609709 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27717303 PubMed]
 
# Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. [http://www.nejm.org/doi/full/10.1056/NEJMoa1607303 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27959613 PubMed]
 
# Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. [http://ascopubs.org/doi/full/10.1200/JCO.2017.75.6155 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28968163 PubMed]
 
# '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains protocol'''
 
 
 
==Letrozole & Palbociclib {{#subobject:da6f2|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen {{#subobject:d4d90|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2971159-3/abstract Finn et al. 2015 (PALOMA-1/TRIO-18)]
 
|style="background-color:#1a9850"|Randomized Phase II
 
|[[#Letrozole_monotherapy_2|Letrozole]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1607303 Finn et al. 2016 (PALOMA-2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Letrozole_monotherapy_2|Letrozole]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
====Therapy====
 
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
*[[Palbociclib (Ibrance)]] 125 mg PO once per day on days 1 to 21
 
 
 
'''28-day cycles, given until progression of disease or unacceptable toxicity'''
 
 
 
===References===
 
# Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2971159-3/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25524798 PubMed]
 
# Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. [http://www.nejm.org/doi/full/10.1056/NEJMoa1607303 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27959613 PubMed]
 
 
 
==Letrozole & Ribociclib {{#subobject:b27d88|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen {{#subobject:66fc2e|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1609709 Hortobagyi et al. 2016 (MONALEESA-2)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Letrozole_monotherapy_2|Letrozole]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|[http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 Tripathy et al. 2017 (MONALEESA-7)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Letrozole_monotherapy_2|Letrozole]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
====Therapy====
 
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
*[[Ribociclib (Kisqali)]] 600 mg PO once per day on days 1 to 21
 
====Supportive medications====
 
*For premenopausal patients:
 
**'''MONALEESA-7:''' [[Goserelin (Zoladex)]] 3.8 mg SC once every 28 days
 
 
 
'''28-day cycles, given until progression of disease or unacceptable toxicity'''
 
 
 
===References===
 
# Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O'Shaughnessy J. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016 Nov 3;375(18):1738-1748. Epub 2016 Oct 7. [http://www.nejm.org/doi/full/10.1056/NEJMoa1609709 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27717303 PubMed]
 
# '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains protocol'''
 
 
 
==Ribociclib & Tamoxifen {{#subobject:93f428|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:e86701|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 Tripathy et al. 2017 (MONALEESA-7)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Tamoxifen_monotherapy_2|Tamoxifen]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
====Therapy====
 
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
*[[Ribociclib (Kisqali)]] 600 mg PO once per day on days 1 to 21
 
====Supportive medications====
 
*[[Goserelin (Zoladex)]] 3.8 mg SC once on day 1
 
 
 
'''28-day cycles'''
 
 
 
===References===
 
# '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains protocol'''
 
 
 
==Tamoxifen monotherapy {{#subobject:dffabd|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen #1, standard dosing (20 mg per day) {{#subobject:497965|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/13/10/2556.long Hayes et al. 1995]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#Toremifene_monotherapy|Toremifene 60 mg per day]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Toremifene 200 mg per day
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://jco.ascopubs.org/content/22/9/1605.long Howell et al. 2004]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Fulvestrant_monotherapy|Fulvestrant]]
 
|style="background-color:#d9ef8b"|Might have superior TTP
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2011.39.0708 Bachelot et al. 2012]
 
|style="background-color:#1a9850"|Randomized Phase II
 
|[[#Tamoxifen_.26_Everolimus|Tamoxifen & Everolimus]]
 
|style="background-color:#d73027"|Inferior OS
 
|-
 
|[http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 Tripathy et al. 2017 (MONALEESA-7)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Ribociclib_.26_Tamoxifen|Ribociclib & Tamoxifen]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
====Supportive medications====
 
*For premenopausal patients:
 
**'''MONALEESA-7:''' [[Goserelin (Zoladex)]] 3.8 mg SC once every 28 days
 
 
 
===Regimen #2, high-dose (40 mg per day) {{#subobject:de3aaf|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://www.springerlink.com/content/pg25l5346057212u/ Gershanovich et al. 1997]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#Toremifene_monotherapy|Toremifene 60 mg per day]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Toremifene 240 mg per day
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223944/ Pyrhönen et al. 1997]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Toremifene_monotherapy|Toremifene 60 mg per day]]
 
|style="background-color:#91cf60"|Seems to have superior TTP
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Tamoxifen (Nolvadex)]] 40 mg PO once per day
 
 
 
===References===
 
# Hayes DF, Van Zyl JA, Hacking A, Goedhals L, Bezwoda WR, Mailliard JA, Jones SE, Vogel CL, Berris RF, Shemano I et al. Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol. 1995 Oct;13(10):2556-66. [http://jco.ascopubs.org/content/13/10/2556.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7595707 PubMed]
 
# Gershanovich M, Garin A, Baltina D, Kurvet A, Kangas L, Ellmén J. A phase III comparison of two toremifene doses to tamoxifen in postmenopausal women with advanced breast cancer. Eastern European Study Group. Breast Cancer Res Treat. 1997 Sep;45(3):251-62. [http://www.springerlink.com/content/pg25l5346057212u/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9386869 PubMed]
 
# Pyrhönen S, Valavaara R, Modig H, Pawlicki M, Pienkowski T, Gundersen S, Bauer J, Westman G, Lundgren S, Blanco G, Mella O, Nilsson I, Hietanen T, Hindy I, Vuorinen J, Hajba A. Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: a randomized double-blind, the 'nordic' phase III study. Br J Cancer. 1997;76(2):270-7. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223944/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/9231932 PubMed]
 
# Howell A, Robertson JF, Abram P, Lichinitser MR, Elledge R, Bajetta E, Watanabe T, Morris C, Webster A, Dimery I, Osborne CK. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol. 2004 May 1;22(9):1605-13. [http://jco.ascopubs.org/content/22/9/1605.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15117982 PubMed]
 
<!-- Presented in part at the 33rd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-12, 2010, and 2011 European Multidisciplinary Cancer Congress, Stockholm, Sweden, September 23-27, 2011. -->
 
# Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaëth D, Legouffe E, Allouache D, El Kouri C, Pujade-Lauraine E. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: A GINECO study. J Clin Oncol. 2012 Aug 1;30(22):2718-24. Epub 2012 May 7. [http://ascopubs.org/doi/full/10.1200/JCO.2011.39.0708 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22565002 PubMed]
 
# '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains protocol'''
 
 
 
See [[#Tamoxifen_monotherapy|references for Tamoxifen (Nolvadex)]]
 
 
 
==Tamoxifen & Everolimus {{#subobject:2abaa9|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen {{#subobject:dd6395|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2011.39.0708 Bachelot et al. 2012]
 
|style="background-color:#1a9850"|Randomized Phase II
 
|[[#Tamoxifen_monotherapy_2|Tamoxifen]]
 
|style="background-color:#1a9850"|Superior OS
 
|-
 
|}
 
====Therapy====
 
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
*[[Everolimus (Afinitor)]] 10 mg PO once per day
 
 
 
'''Given until progression of disease or unacceptable toxicity'''
 
 
 
===References===
 
<!-- Presented in part at the 33rd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-12, 2010, and 2011 European Multidisciplinary Cancer Congress, Stockholm, Sweden, September 23-27, 2011. -->
 
# Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaëth D, Legouffe E, Allouache D, El Kouri C, Pujade-Lauraine E. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: A GINECO study. J Clin Oncol. 2012 Aug 1;30(22):2718-24. Epub 2012 May 7. [http://ascopubs.org/doi/full/10.1200/JCO.2011.39.0708 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22565002 PubMed]
 
 
 
==Toremifene monotherapy {{#subobject:eeba1|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen {{#subobject:32e0dd|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/13/10/2556.long Hayes et al. 1995]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#Tamoxifen_monotherapy_2|Tamoxifen]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Toremifene 200 mg per day
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|rowspan=2|[http://www.springerlink.com/content/pg25l5346057212u/ Gershanovich et al. 1997]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#Tamoxifen_monotherapy_2|Tamoxifen 40 mg per day]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Toremifene 240 mg per day
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223944/ Pyrhönen et al. 1997]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Tamoxifen_monotherapy_2|Tamoxifen 40 mg per day]]
 
|style="background-color:#fc8d59"|Seems to have inferior TTP
 
|-
 
|}
 
====Endocrine therapy====
 
*[[Toremifene (Fareston)]] 60 mg PO once per day
 
 
 
'''Given until progression'''
 
===References===
 
# Hayes DF, Van Zyl JA, Hacking A, Goedhals L, Bezwoda WR, Mailliard JA, Jones SE, Vogel CL, Berris RF, Shemano I et al. Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol. 1995 Oct;13(10):2556-66. [http://jco.ascopubs.org/content/13/10/2556.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7595707 PubMed]
 
# Gershanovich M, Garin A, Baltina D, Kurvet A, Kangas L, Ellmén J. A phase III comparison of two toremifene doses to tamoxifen in postmenopausal women with advanced breast cancer. Eastern European Study Group. Breast Cancer Res Treat. 1997 Sep;45(3):251-62. [http://www.springerlink.com/content/pg25l5346057212u/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9386869 PubMed]
 
# Pyrhönen S, Valavaara R, Modig H, Pawlicki M, Pienkowski T, Gundersen S, Bauer J, Westman G, Lundgren S, Blanco G, Mella O, Nilsson I, Hietanen T, Hindy I, Vuorinen J, Hajba A. Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: a randomized double-blind, the 'nordic' phase III study. Br J Cancer. 1997;76(2):270-7. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223944/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/9231932 PubMed]
 
# [http://www.fareston.com/docs/GTX-Prescribing-Information.pdf Toremifene (Fareston) package insert]
 
 
 
=Metastatic disease, single agent therapy=
 
 
 
==Abemaciclib monotherapy {{#subobject:dcf11a|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:9f24c0|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|[[Overall response rate|'''ORR''']]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581697/ Dickler et al. 2017 (MONARCH 1)]
 
|style="background-color:#91cf60"|Phase II
 
|20% (95% CI 13-27.5)
 
|-
 
|}
 
====Chemotherapy====
 
*[[Abemaciclib (Verzenio)]] 200 mg PO BID
 
 
 
'''Continued until progression'''
 
 
 
===References===
 
# Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, Wildiers H, Hudis CA, O'Shaughnessy J, Zamora E, Yardley DA, Frenzel M, Koustenis A, Baselga J. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 Inhibitor, as a single agent, in patients with refractory HR(+)/HER2(-) metastatic breast cancer. Clin Cancer Res. 2017 Sep 1;23(17):5218-5224. Epub 2017 May 22. [http://clincancerres.aacrjournals.org/content/23/17/5218.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581697/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28533223 PubMed]
 
 
 
==Capecitabine monotherapy {{#subobject:842c42|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen #1, 1250 mg/m<sup>2</sup> BID {{#subobject:fb2810|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/23/10/2155.long Bajetta et al. 2005]
 
|style="background-color:#91cf60"|Phase II
 
|
 
|
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa064320 Geyer et al. 2006]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer,_HER2-positive#Capecitabine_.26_Lapatinib|Capecitabine & Lapatinib]]
 
|style="background-color:#d73027"|Inferior TTP
 
|-
 
|[http://jco.ascopubs.org/content/25/33/5210.long Thomas et al. 2007]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Capecitabine_.26_Ixabepilone|Capecitabine & Ixabepilone]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|[http://jco.ascopubs.org/content/27/12/1999.long von Minckwitz et al. 2009 (GBG 26/BIG 3-05)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer,_HER2-positive#XH|Capecitabine & Trastuzumab]]
 
|style="background-color:#fc8d59"|Seems to have inferior TTP
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903325/ Sparano et al. 2010]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Capecitabine_.26_Ixabepilone|Capecitabine & Ixabepilone]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|[http://jco.ascopubs.org/content/31/23/2870.long Crown et al. 2013]
 
|style="background-color:#1a9850"|Phase III
 
|Capecitabine & Sunitinib
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222915/ Harbeck et al. 2016 (PELICAN)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Doxorubicin_liposomal_monotherapy|Pegylated liposomal doxorubicin]]
 
|style="background-color:#ffffbf"|Inconclusive whether non-inferior
 
|-
 
|[https://link.springer.com/article/10.1007%2Fs10549-016-4075-6 Yamamoto et al. 2016 (JO21095)]
 
|style="background-color:#91cf60"|Non-randomized portion of RCT
 
|
 
|
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30088-8/fulltext Zhang et al. 2017 (BG01-1323L)]
 
|style="background-color:#1a9850"|Phase III
 
|Capecitabine & Utidelone
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Olaparib_monotherapy|Olaparib]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|}
 
''Patients in '''OlympiAD''' had confirmed deleterious or suspected deleterious germline BRCA mutation.''
 
====Preceding treatment====
 
*'''JO21095:''' [[#Docetaxel_monotherapy_3|Docetaxel, with PD]]
 
====Chemotherapy====
 
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO BID on days 1 to 14
 
 
 
'''21-day cycles'''
 
 
 
===Regimen #2, 1000 mg/m<sup>2</sup> BID {{#subobject:674c2d|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/23/10/2155.long Bajetta et al. 2005]
 
|style="background-color:#91cf60"|Phase II
 
|
 
|
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/29/34/4498.long Stockler et al. 2011]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#CMF_2|CMF]]
 
|style="background-color:#91cf60"|Seems to have superior OS
 
|-
 
|Continuous Capecitabine
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Chemotherapy====
 
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID on days 1 to 14
 
 
 
'''21-day cycles'''
 
 
 
===Regimen #3, 650 mg/m<sup>2</sup> BID, continuous {{#subobject:45bb7c|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/29/34/4498.long Stockler et al. 2011]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#CMF_2|CMF]]
 
|style="background-color:#eeee00"|Seems to have superior OS
 
|-
 
|Intermittent Capecitabine
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Chemotherapy====
 
*[[Capecitabine (Xeloda)]] 650 mg/m<sup>2</sup> PO BID
 
 
 
'''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. [http://jco.ascopubs.org/content/23/10/2155.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15710946 PubMed]
 
# Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. [http://www.nejm.org/doi/full/10.1056/NEJMoa064320 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17192538 PubMed]
 
## '''Update:''' Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008 Dec;112(3):533-43. [http://link.springer.com/article/10.1007%2Fs10549-007-9885-0 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18188694 PubMed]
 
## '''Update:''' Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15(9):924-34. [http://theoncologist.alphamedpress.org/content/15/9/924.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228041/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20736298 PubMed]
 
<!-- Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 3, 2007, Chicago, IL. -->
 
# 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. [http://jco.ascopubs.org/content/25/33/5210.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17968020 PubMed]
 
# von Minckwitz G, du Bois A, Schmidt M, Maass N, Cufer T, de Jongh FE, Maartense E, Zielinski C, Kaufmann M, Bauer W, Baumann KH, Clemens MR, Duerr R, Uleer C, Andersson M, Stein RC, Nekljudova V, Loibl S. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study. J Clin Oncol. 2009 Apr 20;27(12):1999-2006. Epub 2009 Mar 16. [http://jco.ascopubs.org/content/27/12/1999.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19289619 PubMed]
 
## '''Update:''' von Minckwitz G, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, Maartense E, de Jongh FE, Baumann KH, Bischoff J, Harbeck N, Lück HJ, Maass N, Zielinski C, Andersson M, Stein RC, Nekljudova V, Loibl S; GBG 26/BIG 03-05 study group and participating investigators. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer. 2011 Oct;47(15):2273-81. Epub 2011 Jul 7. [http://www.ejcancer.com/article/S0959-8049(11)00425-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21741829 PubMed]
 
<!-- Presented in part at the American Society of Clinical Oncology Breast Cancer Symposium, September 5-7, 2008, Washington, DC (abstr 186). -->
 
# 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.[http://jco.ascopubs.org/content/28/20/3256.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903325/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20530276 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. -->
 
# 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. [http://jco.ascopubs.org/content/29/34/4498.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22025143 PubMed]
 
<!-- Presented in part at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 
# 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. [http://jco.ascopubs.org/content/31/23/2870.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23857972 PubMed]
 
# 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://link.springer.com/article/10.1007%2Fs10549-016-4033-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222915/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27798749 PubMed]
 
# 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://link.springer.com/article/10.1007%2Fs10549-016-4075-6 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28005247 PubMed]
 
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30088-8/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28209298 PubMed]
 
# Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. [http://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28578601 PubMed]
 
 
 
==Docetaxel monotherapy {{#subobject:47db8e|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
D: '''<u>D</u>'''ocetaxel
 
<br>T: '''<u>T</u>'''axotere (Docetaxel)
 
===Regimen #1, 70 mg/m<sup>2</sup> {{#subobject:a74e46|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[https://link.springer.com/article/10.1007%2Fs10549-016-4075-6 Yamamoto et al. 2016 (JO21095)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Capecitabine_.26_Docetaxel|Capecitabine & Docetaxel]]
 
|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'''
 
 
 
'At progression, this arm was pre-assigned to transition to [[#Capecitabine_monotherapy_2|capecitabine]].''
 
 
 
===Regimen #2, 100 mg/m<sup>2</sup> {{#subobject:bf6578|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/17/8/2341.long Chan et al. 1999 (303 Study Group)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Doxorubicin_monotherapy|Doxorubicin]]
 
|style="background-color:#1a9850"|Superior ORR
 
|-
 
|[http://jco.ascopubs.org/content/20/12/2812.long O'Shaughnessy et al. 2002]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Capecitabine_.26_Docetaxel|Capecitabine & Docetaxel]]
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|[http://jco.ascopubs.org/content/23/19/4265.long Marty et al. 2005 (M77001)]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer,_HER2-positive#TH_.28Taxotere.29_3|Docetaxel & Trastuzumab]]
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/24/31/4963.long Harvey et al. 2006]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|Low-dose q3wk docetaxel
 
|style="background-color:#d9ef8b"|Might have superior TTP
 
|-
 
|Lower-dose q3wk docetaxel
 
|style="background-color:#d9ef8b"|Might have superior TTP
 
|-
 
|rowspan=3|[http://jco.ascopubs.org/content/27/22/3611.long Gradishar et al. 2009]
 
|rowspan=3 style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel.2C_nanoparticle_albumin-bound_monotherapy_2|Higher-dose weekly nanoparticle albumin-bound paclitaxel]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|[[#Paclitaxel.2C_nanoparticle_albumin-bound_monotherapy_2|Lower-dose weekly nanoparticle albumin-bound paclitaxel]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[[#Paclitaxel.2C_nanoparticle_albumin-bound_monotherapy_2|q3wk nanoparticle albumin-bound paclitaxel]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Chemotherapy====
 
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 
 
 
'''21-day cycles'''
 
 
 
''Note: the '''303 Study Group''' stopped treatment after 7 cycles.''
 
 
 
===Regimen #3, 60 mg/m<sup>2</sup> q3wk {{#subobject:cf6000|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
![[Levels_of_Evidence#Toxicity|Toxicity]]
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/24/31/4963.long Harvey et al. 2006]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|Lower-dose q3wk docetaxel
 
|style="background-color:#fee08b"|Might have inferior TTP
 
|
 
|-
 
|Standard-dose q3wk docetaxel
 
|style="background-color:#fee08b"|Might have inferior TTP
 
|
 
|-
 
|[http://www.sciencedirect.com/science/article/pii/S1470204515004118 Takashima et al. 2015 (SELECT BC)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#S-1_monotherapy|S-1]]
 
|style="background-color:#eeee00"|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 cycles'''
 
 
 
===Regimen #4, 60 mg/m<sup>2</sup> q4wk {{#subobject:c5cf8d|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
![[Levels_of_Evidence#Toxicity|Toxicity]]
 
|-
 
|[http://www.sciencedirect.com/science/article/pii/S1470204515004118 Takashima et al. 2015 (SELECT BC)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#S-1_monotherapy|S-1]]
 
|style="background-color:#eeee00"|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 #5, 75 mg/m<sup>2</sup> q3wk {{#subobject:32c5e5|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
![[Levels_of_Evidence#Toxicity|Toxicity]]
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/24/31/4963.long Harvey et al. 2006]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|Low-dose q3wk docetaxel
 
|style="background-color:#d9ef8b"|Might have superior TTP
 
|
 
|-
 
|Standard-dose q3wk docetaxel
 
|style="background-color:#fee08b"|Might have inferior TTP
 
|
 
|-
 
|[http://www.sciencedirect.com/science/article/pii/S1470204515004118 Takashima et al. 2015 (SELECT BC)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#S-1_monotherapy|S-1]]
 
|style="background-color:#eeee00"|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
 
 
 
'''21-day cycles'''
 
 
 
===Regimen #6, 75 mg/m<sup>2</sup> q4wk {{#subobject:79ac92|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
![[Levels_of_Evidence#Toxicity|Toxicity]]
 
|-
 
|[http://www.sciencedirect.com/science/article/pii/S1470204515004118 Takashima et al. 2015 (SELECT BC)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#S-1_monotherapy|S-1]]
 
|style="background-color:#eeee00"|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 #7, 40 mg/m<sup>2</sup> weekly (6 out of 8) {{#subobject:6ed28b|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://jco.ascopubs.org/content/18/6/1212.long Burstein et al. 2000]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
====Chemotherapy====
 
*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV once per week for weeks 1 to 6, then off for weeks 7 & 8
 
 
 
'''8-week cycles'''
 
 
 
===References===
 
# '''Review:''' Burris HA 3rd. Single-agent docetaxel (Taxotere) in randomized phase III trials. Semin Oncol. 1999 Jun;26(3 Suppl 9):1-6. [https://www.ncbi.nlm.nih.gov/pubmed/10426452 PubMed]
 
# 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. [http://jco.ascopubs.org/content/17/8/2341.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10561296 PubMed]
 
# Alexandre J, Bleuzen P, Bonneterre J, Sutherland W, Misset JL, Guastalla J, Viens P, Faivre S, Chahine A, Spielman M, Bensmaïne A, Marty M, Mahjoubi M, Cvitkovic E. Factors predicting for efficacy and safety of docetaxel in a compassionate-use cohort of 825 heavily pretreated advanced breast cancer patients. J Clin Oncol. 2000 Feb;18(3):562-73. [http://jco.ascopubs.org/content/18/3/562.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10653871 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. [http://jco.ascopubs.org/content/18/6/1212.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10715290 PubMed] content property of [http://hemonc.org HemOnc.org]
 
# 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. [http://jco.ascopubs.org/content/20/12/2812.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12065558 PubMed]
 
# Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005 Jul 1;23(19):4265-74. Epub 2005 May 23. [http://jco.ascopubs.org/content/23/19/4265.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15911866 PubMed]
 
# 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. [http://jco.ascopubs.org/content/24/31/4963.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17033039 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. [http://jco.ascopubs.org/content/27/22/3611.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19470941 PubMed]
 
# 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. [http://www.sciencedirect.com/science/article/pii/S1470204515004118 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26617202 PubMed]
 
## '''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://link.springer.com/article/10.1007%2Fs11136-016-1388-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288429/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27517267 PubMed]
 
# 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://link.springer.com/article/10.1007%2Fs10549-016-4075-6 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28005247 PubMed]
 
 
 
==Doxorubicin monotherapy {{#subobject:8a2b88|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen #1 {{#subobject:cf8189|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://annonc.oxfordjournals.org/content/15/3/440.long O'Brien et al. 2004 (CAELYX Breast Cancer Study Group)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Doxorubicin_liposomal_monotherapy|Pegylated liposomal doxorubicin]]
 
|style="background-color:#eeee00"|Seems to have non-inferior PFS
 
|-
 
|}
 
====Chemotherapy====
 
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
 
 
'''21-day cycles'''
 
 
 
===Regimen #2 {{#subobject:acc23b|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/17/8/2341.long Chan et al. 1999 (303 Study Group)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#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 #3 {{#subobject:96cac2|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.sciencedirect.com/science/article/pii/0277537986900751 Gundersen et al. 1986]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer_-_obsolete#VAC|VAC]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Chemotherapy====
 
*[[Doxorubicin (Adriamycin)]] 20 mg/m<sup>2</sup> IV once per week
 
 
 
'''Duration not specified'''
 
 
 
===References===
 
# 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. [http://www.sciencedirect.com/science/article/pii/0277537986900751 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/3595668 PubMed]
 
# 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. [http://jco.ascopubs.org/content/17/8/2341.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10561296 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. [http://annonc.oxfordjournals.org/content/15/3/440.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14998846 PubMed]
 
 
 
==Doxorubicin liposomal monotherapy {{#subobject:2b08a6|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:6ebaf9|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://annonc.oxfordjournals.org/content/15/3/440.long O'Brien et al. 2004 (CAELYX Breast Cancer Study Group)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Doxorubicin_monotherapy|Doxorubicin]]
 
|style="background-color:#eeee00"|Seems to have non-inferior PFS
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222915/ Harbeck et al. 2016 (PELICAN)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Capecitabine_monotherapy_2|Capecitabine]]
 
|style="background-color:#ffffbf"|Inconclusive whether non-inferior
 
|-
 
|}
 
====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. [http://annonc.oxfordjournals.org/content/15/3/440.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14998846 PubMed]
 
# 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://link.springer.com/article/10.1007%2Fs10549-016-4033-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222915/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27798749 PubMed]
 
 
 
==Epirubicin monotherapy {{#subobject:e941f2|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen #1, 40 mg/m<sup>2</sup> {{#subobject:740b22|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=3|[http://jco.ascopubs.org/content/14/4/1146.long Bastholt et al. 1996]
 
|rowspan=3 style="background-color:#1a9850"|Phase III
 
|Epirubicin 60 mg/m<sup>2</sup>
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Epirubicin 90 mg/m<sup>2</sup>
 
|style="background-color:#d73027"|Inferior TTP
 
|-
 
|Epirubicin 135 mg/m<sup>2</sup>
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Chemotherapy====
 
*[[Epirubicin (Ellence)]] 40 mg/m<sup>2</sup> IV once on day 1
 
 
 
'''21-day cycles'''
 
 
 
===Regimen #2, 60 mg/m<sup>2</sup> {{#subobject:5b43d9|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=3|[http://jco.ascopubs.org/content/14/4/1146.long Bastholt et al. 1996]
 
|rowspan=3 style="background-color:#1a9850"|Phase III
 
|Epirubicin 40 mg/m<sup>2</sup>
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Epirubicin 90 mg/m<sup>2</sup>
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Epirubicin 135 mg/m<sup>2</sup>
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Chemotherapy====
 
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
 
 
 
'''21-day cycles'''
 
 
 
===Regimen #3, 90 mg/m<sup>2</sup> {{#subobject:e56ea6|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=3|[http://jco.ascopubs.org/content/14/4/1146.long Bastholt et al. 1996]
 
|rowspan=3 style="background-color:#1a9850"|Phase III
 
|Epirubicin 40 mg/m<sup>2</sup>
 
|style="background-color:#1a9850"|Superior TTP
 
|-
 
|Epirubicin 60 mg/m<sup>2</sup>
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Epirubicin 135 mg/m<sup>2</sup>
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Chemotherapy====
 
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
 
 
 
'''21-day cycles'''
 
 
 
===Regimen #4, 135 mg/m<sup>2</sup> {{#subobject:e0a80d|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=3|[http://jco.ascopubs.org/content/14/4/1146.long Bastholt et al. 1996]
 
|rowspan=3 style="background-color:#1a9850"|Phase III
 
|Epirubicin 40 mg/m<sup>2</sup>
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Epirubicin 60 mg/m<sup>2</sup>
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Epirubicin 90 mg/m<sup>2</sup>
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====Chemotherapy====
 
*[[Epirubicin (Ellence)]] 135 mg/m<sup>2</sup> IV once on day 1
 
 
 
'''21-day cycles'''
 
 
 
===References===
 
# Bastholt L, Dalmark M, Gjedde SB, Pfeiffer P, Pedersen D, Sandberg E, Kjaer M, Mouridsen HT, Rose C, Nielsen OS, Jakobsen P, Bentzen SM. 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. [http://jco.ascopubs.org/content/14/4/1146.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8648369 PubMed]
 
 
 
==Eribulin monotherapy {{#subobject:ef2415|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:25ef0|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960070-6/fulltext Cortes et al. 2011 (EMBRACE)]
 
|style="background-color:#1a9850"|Phase III
 
|Investigator's choice
 
|style="background-color:#91cf60"|Seems to have superior OS
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Olaparib_monotherapy|Olaparib]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|}
 
''Patients in '''OlympiAD''' had confirmed deleterious or suspected deleterious germline BRCA mutation.''
 
====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===
 
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960070-6/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21376385 PubMed]
 
# Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. [http://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28578601 PubMed]
 
 
 
==Gemcitabine monotherapy {{#subobject:af0915|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:4db8d|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://jco.ascopubs.org/content/13/11/2731.long Carmichael et al. 1995]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|[http://www.karger.com/Article/Abstract/58524 Spielmann et al. 2001]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
====Chemotherapy====
 
*[[Gemcitabine (Gemzar)]] 800 to 1200 mg/m<sup>2</sup> IV 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. [http://jco.ascopubs.org/content/13/11/2731.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/11408796 PubMed]
 
 
 
==Olaparib monotherapy {{#subobject:a019cd|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen #1 {{#subobject:3b0774|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Capecitabine_monotherapy_2|Capecitabine]]<br> [[#Eribulin_monotherapy|Eribulin]]<br> [[#Vinorelbine_monotherapy_2|Vinorelbine]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
''Patients had confirmed deleterious or suspected deleterious germline BRCA mutation.''
 
====Chemotherapy====
 
*[[Olaparib (Lynparza)]] 300 mg PO BID
 
 
 
'''Continued until progression'''
 
 
 
===Regimen #2 {{#subobject:31cf8c|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60892-6/fulltext Tutt et al. 2010]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|[http://jco.ascopubs.org/content/33/3/244.long Kaufman et al. 2014]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
''Patients in '''Kaufman et al. 2014''' had germline BRCA1/2 mutations and had progressed after at least three lines of treatment for metastatic disease.''
 
====Chemotherapy====
 
*[[Olaparib (Lynparza)]] 400 mg PO BID
 
 
 
'''Continued until progression'''
 
 
 
===Regimen #3 {{#subobject:31ed8c|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60892-6/fulltext Tutt et al. 2010]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
====Chemotherapy====
 
*[[Olaparib (Lynparza)]] 100 mg PO BID
 
 
 
'''Continued until progression'''
 
 
 
===References===
 
# Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):235-44. Epub 2010 Jul 6. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60892-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20609467 PubMed]
 
<!-- Presented at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013. -->
 
# Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. [http://jco.ascopubs.org/content/33/3/244.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25366685 PubMed]
 
# Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. [http://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28578601 PubMed]
 
 
 
==Paclitaxel monotherapy {{#subobject:3e5448|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
 
===Regimen #1, 175 mg/m<sup>2</sup> q3wk dosing {{#subobject:72389a|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
![[Levels_of_Evidence#Toxicity|Toxicity]]
 
|-
 
|[http://jco.ascopubs.org/content/13/10/2575.long Seidman et al. 1995]
 
|style="background-color:#91cf60"|Phase II
 
|
 
|
 
|
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJM200103153441101 Slamon et al. 2001]
 
|style="background-color:#1a9850"|Phase III
 
|[[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH]]
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|
 
|-
 
|[http://jco.ascopubs.org/content/23/31/7794.long Gradishar et al. 2005]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel.2C_nanoparticle_albumin-bound_monotherapy_2|Nanoparticle albumin-bound paclitaxel]]
 
|style="background-color:#d73027"|Inferior TTP
 
|
 
|-
 
|[http://jco.ascopubs.org/content/26/10/1642.long Seidman et al. 2008 (CALGB 9840)]
 
|style="background-color:#1a9850"|Phase III
 
|Weekly paclitaxel
 
|style="background-color:#d73027"|Inferior OS
 
|
 
|-
 
|[http://jco.ascopubs.org/content/26/24/3950.long Albain et al. 2008]
 
|style="background-color:#1a9850"|Phase III
 
|[[#GT_.28Taxol.29|Gemcitabine & Paclitaxel]]
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|
 
|-
 
|[http://www.sciencedirect.com/science/article/pii/S1470204515004118 Takashima et al. 2015 (SELECT BC)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#S-1_monotherapy|S-1]]
 
|style="background-color:#eeee00"|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
 
 
 
'''21-day cycles'''
 
 
 
===Regimen #2, 175 mg/m<sup>2</sup> q4wk dosing {{#subobject:42c791|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
![[Levels_of_Evidence#Toxicity|Toxicity]]
 
|-
 
|[http://www.sciencedirect.com/science/article/pii/S1470204515004118 Takashima et al. 2015 (SELECT BC)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#S-1_monotherapy|S-1]]
 
|style="background-color:#eeee00"|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 #3, 80 mg/m<sup>2</sup> weekly dosing {{#subobject:718d5b|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/19/22/4216.long Perez et al. 2001]
 
|style="background-color:#91cf60"|Phase II
 
|
 
|
 
|-
 
|[http://jco.ascopubs.org/content/26/10/1642.long Seidman et al. 2008 (CALGB 9840)]
 
|style="background-color:#1a9850"|Phase III
 
|Every three-week paclitaxel
 
|style="background-color:#1a9850"|Superior OS
 
|-
 
|}
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per week
 
 
 
'''28-day cycles'''
 
 
 
===Regimen #4, 3 weeks on, 1 week off {{#subobject:1a1adf|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
![[Levels_of_Evidence#Toxicity|Toxicity]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa072113 Miller et al. 2007]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]
 
|style="background-color:#d73027"|Inferior PFS
 
|
 
|-
 
|[http://www.sciencedirect.com/science/article/pii/S1470204515004118 Takashima et al. 2015 (SELECT BC)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#S-1_monotherapy|S-1]]
 
|style="background-color:#eeee00"|Seems to have non-inferior OS
 
|style="background-color:#d73027"|Inferior EQ-5D score
 
|-
 
|[http://www.ejcancer.com/article/S0959-8049(16)32470-4/fulltext Miles et al. 2016 (MERiDiAN)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]
 
|style="background-color:#d73027"|Inferior PFS
 
|
 
|-
 
|}
 
''Note: both '''Miller et al. 2007''' and '''MERiDiAN''' specified 90 mg/m<sup>2</sup>; '''SELECT BC''' gave a range of 80 to 100 mg/m<sup>2</sup>.''
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 80 to 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
 
 
'''28-day cycles'''
 
 
 
===Regimen #5, 250 mg/m<sup>2</sup> q3wk dosing {{#subobject:6282a2|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://jco.ascopubs.org/content/13/10/2575.long Seidman et al. 1995]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
''Note: this is the dose used in untreated patients in Seidman et al. 1995. It is not a common dosing.''
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 250 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 et al. 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. [http://jco.ascopubs.org/content/13/10/2575.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7595709 PubMed]
 
# Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. [http://www.nejm.org/doi/full/10.1056/NEJM200103153441101 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11248153 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. [http://jco.ascopubs.org/content/19/22/4216.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11709565 PubMed]
 
<!-- Presented in part at the 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003. -->
 
# 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. [http://jco.ascopubs.org/content/23/31/7794.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16172456 PubMed]
 
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa072113 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18160686 PubMed]
 
<!-- Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA. -->
 
# 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. [http://jco.ascopubs.org/content/26/10/1642.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18375893 PubMed]
 
<!-- 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. [http://jco.ascopubs.org/content/26/24/3950.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18711184 PubMed]
 
# 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. [http://www.sciencedirect.com/science/article/pii/S1470204515004118 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26617202 PubMed]
 
## '''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://link.springer.com/article/10.1007%2Fs11136-016-1388-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288429/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27517267 PubMed]
 
# 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. [http://www.ejcancer.com/article/S0959-8049(16)32470-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27817944 PubMed]
 
 
 
==Paclitaxel, nanoparticle albumin-bound monotherapy {{#subobject:5dc417|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Example orders===
 
*[[Example orders for Paclitaxel, nanoparticle albumin-bound (Abraxane) in breast cancer]]
 
 
 
===Regimen #1, weekly dosing (100 mg/m<sup>2</sup>) {{#subobject:f0096c|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=3|[http://jco.ascopubs.org/content/27/22/3611.long Gradishar et al. 2009]
 
|rowspan=3 style="background-color:#1a9850"|Randomized Phase II
 
|[[#Docetaxel_monotherapy_3|Docetaxel]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Weekly nab-paclitaxel (150 mg/m<sup>2</sup>)
 
|Not reported
 
|-
 
|q3wk nab-paclitaxel
 
|Not reported
 
|-
 
|}
 
====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 #2, weekly dosing (150 mg/m<sup>2</sup>) {{#subobject:f0096c|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=3|[http://jco.ascopubs.org/content/27/22/3611.long Gradishar et al. 2009]
 
|rowspan=3 style="background-color:#1a9850"|Randomized Phase II
 
|[[#Docetaxel_monotherapy_3|Docetaxel]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|Weekly nab-paclitaxel (100 mg/m<sup>2</sup>)
 
|Not reported
 
|-
 
|q3wk nab-paclitaxel
 
|Not reported
 
|-
 
|}
 
====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 #3, q3wk nab-paclitaxel {{#subobject:11b87e|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=3|[http://jco.ascopubs.org/content/27/22/3611.long Gradishar et al. 2009]
 
|rowspan=3 style="background-color:#1a9850"|Randomized Phase II
 
|[[#Docetaxel_monotherapy_3|Docetaxel]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|Weekly nab-paclitaxel (100 mg/m<sup>2</sup>)
 
|Not reported
 
|-
 
|Weekly nab-paclitaxel (150 mg/m<sup>2</sup>)
 
|Not reported
 
|-
 
|}
 
====Chemotherapy====
 
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 300 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
 
 
'''21-day cycles'''
 
 
 
===Regimen #4 {{#subobject:bf6371|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/23/31/7794.long Gradishar et al. 2005]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel_monotherapy_3|Paclitaxel]]
 
|style="background-color:#1a9850"|Superior TTP
 
|-
 
|}
 
====Chemotherapy====
 
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 260 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
 
 
====Supportive medications====
 
*No corticosteroid or antihistamine premedication
 
 
 
'''21-day cycles'''
 
 
 
 
===References===
 
===References===
<!-- Presented in part at the 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003. -->
+
#'''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]
# 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. [http://jco.ascopubs.org/content/23/31/7794.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16172456 PubMed]
+
Start of hidden/commented information for virtual editor End of hidden/commented information for virtual editor
<!-- 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. [http://jco.ascopubs.org/content/27/22/3611.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19470941 PubMed]
 
 
 
==Pemetrexed monotherapy {{#subobject:93e4ed|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen #1 {{#subobject:a2f6d|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.springerlink.com/content/b1354n1r36631118 Robert et al. 2011]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
====Chemotherapy====
 
*[[Pemetrexed (Alimta)]] 600 mg/m<sup>2</sup> IV once on day 1
 
  
====Supportive medications====
 
*[[Dexamethasone (Decadron)]] 4 mg PO BID the day before, day of, and day after chemotherapy
 
*Folic acid 350 to 1000 mcg PO once per day, to start at least 5 days prior to start of pemetrexed therapy, to continue throughout therapy with pemetrexed, 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 therapy, to continue throughout therapy with pemetrexed, and until 3 weeks after the last dose of pemetrexed
 
  
'''14-day cycles, given until progression of disease or unacceptable toxicity'''
 
 
===Regimen #2 {{#subobject:b49e6b|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://clincancerres.aacrjournals.org/content/12/3/832.long Gomez et al. 2006]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
 
''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 medications====
 
*[[Dexamethasone (Decadron)]] 4 mg PO BID the day before, day of, and day after chemotherapy
 
*Folic acid 350 to 1000 mcg PO once per day, to start 5 to 7 days prior to start of pemetrexed therapy, to continue throughout therapy with pemetrexed
 
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, the first dose given before the study's pretreatment biopsy, to continue throughout therapy with pemetrexed
 
 
'''21-day cycle for up to 3 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://www.springerlink.com/content/b1354n1r36631118 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21188632 PubMed]
 
 
==S-1 monotherapy {{#subobject:7702f2|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:48e547|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
![[Levels_of_Evidence#Toxicity|Toxicity]]
 
|-
 
|[http://www.sciencedirect.com/science/article/pii/S1470204515004118 Takashima et al. 2015 (SELECT BC)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Docetaxel_monotherapy_3|Docetaxel]]<br> [[#Paclitaxel_monotherapy_3|Paclitaxel]]
 
|style="background-color:#eeee00"|Seems to have non-inferior OS
 
|style="background-color:#1a9850"|Superior EQ-5D score
 
|-
 
|}
 
====Chemotherapy====
 
*[[Tegafur, gimeracil, oteracil (S-1)]] as follows:
 
**BSA less than 1.25 m<sup>2</sup>: 40 mg PO BID 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 BID on days 1 to 28
 
**BSA 1.5 m<sup>2</sup> or more: 60 mg PO BID on days 1 to 28
 
 
'''42-day cycles'''
 
 
===References===
 
# 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. [http://www.sciencedirect.com/science/article/pii/S1470204515004118 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26617202 PubMed]
 
## '''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://link.springer.com/article/10.1007%2Fs11136-016-1388-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288429/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27517267 PubMed]
 
 
==Vinorelbine monotherapy {{#subobject:5c104c|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen #1 {{#subobject:7321fd|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Olaparib_monotherapy|Olaparib]]
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|}
 
''Patients had confirmed deleterious or suspected deleterious germline BRCA mutation.''
 
====Chemotherapy====
 
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
 
'''21-day cycles'''
 
 
===Regimen #2, weekly dosing {{#subobject:c0c952|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://jco.ascopubs.org/content/12/10/2094.long Gasparini et al. 1994]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pubmed/11745280 Zelek et al. 2001]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
====Chemotherapy====
 
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per week
 
 
===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. [http://jco.ascopubs.org/content/12/10/2094.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7931479 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://www.ncbi.nlm.nih.gov/pubmed/11745280 PubMed]
 
# Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. [http://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28578601 PubMed]
 
 
=Metastatic disease, combination chemotherapy=
 
==AC {{#subobject:843320|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
AC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
 
 
===Regimen {{#subobject:2e4988|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/8/9/1483.long Fisher et al. 1990 (NSABP B-15)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|AC, then CMF
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[[#CMF_2|CMF]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJM200103153441101 Slamon et al. 2001]
 
|style="background-color:#1a9850"|Phase III
 
|[[#ACH|ACH]]
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|[http://jco.ascopubs.org/content/21/6/968.long Nabholtz et al. 2003]
 
|style="background-color:#1a9850"|Phase III
 
|[[#AT_.28Taxotere.29|AT (Taxotere)]]
 
|style="background-color:#fc8d59"|Seems to have inferior TTP
 
|-
 
|}
 
''Note: patients in Slamon et al. 2001 had not previously received adjuvant (postoperative) therapy with an anthracycline.''
 
====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'''
 
 
===References===
 
# Jones SE, Durie BG, Salmon SE. Combination chemotherapy with adriamycin and cyclophosphamide for advanced breast cancer. Cancer. 1975 Jul;36(1):90-7. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197507)36:1%3C90::AID-CNCR2820360104%3E3.0.CO;2-H/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1203853 PubMed]
 
# Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, Bowman D, Wolmark N, Wickerham DL, Kardinal CG et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990 Sep;8(9):1483-96. [http://jco.ascopubs.org/content/8/9/1483.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2202791 PubMed]
 
# Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. [http://www.nejm.org/doi/full/10.1056/NEJM200103153441101 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11248153 PubMed]
 
# Nabholtz JM, Falkson C, Campos D, Szanto J, Martin 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. [http://jco.ascopubs.org/content/21/6/968.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12637459 PubMed]
 
 
==AT (Taxol) {{#subobject:86ac2d|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
AT: '''<u>A</u>'''driamycin, '''<u>T</u>'''axol
 
 
===Regimen {{#subobject:1f6e13|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://jco.ascopubs.org/content/13/11/2688.long Gianni et al. 1995]
 
|style="background-color:#EEEE00"|Non-randomized
 
|-
 
|}
 
====Chemotherapy====
 
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
*[[Paclitaxel (Taxol)]] 125-200 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 et al. 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. [http://jco.ascopubs.org/content/13/11/2688.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7595726 PubMed]
 
 
==AT (Taxotere) {{#subobject:145802|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
AT: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>T</u>'''axotere (Docetaxel)
 
 
===Regimen {{#subobject:9c6b82|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/21/6/968.long Nabholtz et al. 2003]
 
|style="background-color:#1a9850"|Phase III
 
|[[#AC_3|AC]]
 
|style="background-color:#91cf60"|Seems to have superior TTP
 
|-
 
|}
 
====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 cycles'''
 
 
===References===
 
# Nabholtz JM, Falkson C, Campos D, Szanto J, Martin 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. [http://jco.ascopubs.org/content/21/6/968.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12637459 PubMed]
 
 
==Capecitabine & Bevacizumab {{#subobject:14a8f1|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:b1de3e|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788680/ Welt et al. 2016 (CARIN)]
 
|style="background-color:#1a9850"|Phase III
 
|Capecitabine, Vinorelbine, Bevacizumab
 
|style="background-color:#fee08b"|Might have inferior PFS
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30154-1/fulltext Zielinski et al. 2016 (TURANDOT)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel_.26_Bevacizumab|Paclitaxel & Bevacizumab]]
 
|style="background-color:#eeee00"|Non-inferior OS
 
|-
 
|}
 
====Chemotherapy====
 
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID on days 1 to 14
 
*[[Bevacizumab (Avastin)]] 10 to 15 mg/kg IV once on day 1
 
 
'''21-day cycles'''
 
 
===References===
 
# 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788680/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26927446 PubMed]
 
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30154-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27501767 PubMed]
 
 
==Capecitabine & Docetaxel {{#subobject:a11c57|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
TX: '''<u>T</u>'''axotere (Docetaxel) and '''<u>X</u>'''eloda (Capecitabine)
 
<br>XT: '''<u>X</u>'''eloda (Capecitabine) and '''<u>T</u>'''axotere (Docetaxel)
 
===Regimen #1, 825/60 {{#subobject:5bcf6a|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[https://link.springer.com/article/10.1007%2Fs10549-016-4075-6 Yamamoto et al. 2016 (JO21095)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Docetaxel_monotherapy_3|Docetaxel]]
 
|style="background-color:#91cf60"|Seems to have superior PFS
 
|-
 
|}
 
====Chemotherapy====
 
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO BID days 1 to 14
 
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 
 
'''21-day cycles'''
 
 
===Regimen #2, 1250/75 {{#subobject:6c7dba|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/20/12/2812.long O'Shaughnessy et al. 2002]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Docetaxel_monotherapy_3|Docetaxel]]
 
|style="background-color:#91cf60"|Seems to have superior OS
 
|-
 
|}
 
====Chemotherapy====
 
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO BID 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. [http://jco.ascopubs.org/content/20/12/2812.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12065558 PubMed]
 
# 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://link.springer.com/article/10.1007%2Fs10549-016-4075-6 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28005247 PubMed]
 
 
==Capecitabine & Ixabepilone {{#subobject:9ce286|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:f5cae3|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/25/33/5210.long Thomas et al. 2007]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Capecitabine_monotherapy_2|Capecitabine]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903325/ Sparano et al. 2010]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Capecitabine_monotherapy_2|Capecitabine]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
====Chemotherapy====
 
*[[Capecitabine (Xeloda)]] 2000 mg/m<sup>2</sup> PO once 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. -->
 
# 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. [http://jco.ascopubs.org/content/25/33/5210.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17968020 PubMed]
 
<!-- Presented in part at the American Society of Clinical Oncology Breast Cancer Symposium, September 5-7, 2008, Washington, DC (abstr 186). -->
 
# 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. [http://jco.ascopubs.org/content/28/20/3256.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903325/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20530276 PubMed]
 
 
==Capecitabine & Paclitaxel {{#subobject:bd0f63|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
TX: '''<u>T</u>'''axol (Paclitaxel), '''<u>X</u>'''eloda (Capecitabine)
 
 
===Regimen {{#subobject:74e9d|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://jco.ascopubs.org/content/24/27/4384.long Blum et al. 2006]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
====Chemotherapy====
 
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> (rounded to nearest 500 mg) PO BID on days 1 to 14
 
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
 
'''21-day cycles, given until progression of disease or unacceptable toxicity'''
 
 
===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. [http://jco.ascopubs.org/content/24/27/4384.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16926223 PubMed]
 
 
==Capecitabine & Paclitaxel, nanoparticle albumin-bound {{#subobject:821a8e|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:e2b0d2|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.clinical-breast-cancer.com/article/S1526-8209(11)00206-0/fulltext Schwartzberg et al. 2011]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
====Chemotherapy====
 
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> (rounded to nearest 500 mg) PO BID 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, given until progression of disease or unacceptable toxicity'''
 
 
===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/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22154117 PubMed]
 
 
==Carboplatin & Gemcitabine {{#subobject:83a5ee|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:e571d|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://www.clinical-breast-cancer.com/article/S1526-8209(11)70540-7/abstract Nagourney et al. 2008]
 
|style="background-color:#d9ef8b"|Pilot, <20 pts
 
|-
 
|}
 
====Chemotherapy====
 
*[[Carboplatin (Paraplatin)]] AUC 2 IV over 1 hour once per day on days 1 & 8
 
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 & 8
 
 
'''21-day cycles, given until complete remission, progression of disease, or unacceptable toxicity'''
 
 
===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/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18952557 PubMed]
 
 
==Cisplatin & Vinorelbine {{#subobject:c1c866|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
===Regimen {{#subobject:9caba1|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pubmed/9428489 Ray-Coquard et al. 1998]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|[http://annonc.oxfordjournals.org/content/11/9/1155.long Vassilomanolakis et al. 2000]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
====Chemotherapy====
 
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 hour 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 medications====
 
*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 (infusion rate: 500 mL/H) once prior to [[Cisplatin (Platinol)]]
 
*[[Furosemide (Lasix)]] 40 mg IV once 20 minutes prior to [[Cisplatin (Platinol)]]
 
*Normal saline 1000 mL and D5W 1000 mL IV over 4 hours (overall infusion rate: 500 mL/H; paper did not say whether fluids were given sequentially or concurrently) once after [[Cisplatin (Platinol)]]
 
*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonists]] used
 
 
'''21-day cycle for up to 6 cycles or progression of disease'''
 
 
===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://www.ncbi.nlm.nih.gov/pubmed/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. [http://annonc.oxfordjournals.org/content/11/9/1155.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11061611 Pubmed]
 
 
==CMF {{#subobject:9c9c1d|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
CMF: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
 
===Regimen {{#subobject:4a77d3|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J/abstract Bull et al. 1978]
 
|style="background-color:#1a9850"|Phase III
 
|[[#FAC_2|CAF]]
 
|style="background-color:#fee08b"|Might have inferior ORR
 
|-
 
|rowspan=2|[http://jco.ascopubs.org/content/8/9/1483.long Fisher et al. 1990 (NSABP B-15)]
 
|rowspan=2 style="background-color:#1a9850"|Phase III
 
|[[#AC_3|AC]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|AC, then CMF
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJM200004133421501 Stadtmauer et al. 2000 (Philadelphia Bone Marrow Transplant Group)]
 
|style="background-color:#1a9850"|Phase III
 
|CMF x 4-6, then HDT
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|[http://jco.ascopubs.org/content/19/4/943.long Ackland et al. 2001 (HEPI 013)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#FEC_3|CEF]]
 
|style="background-color:#d73027"|Inferior TTP
 
|-
 
|[http://jco.ascopubs.org/content/29/34/4498.long Stockler et al. 2011]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Capecitabine_monotherapy_2|Continuous Capecitabine]]<br> [[#Capecitabine_monotherapy_2|Intermittent Capecitabine]]
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|}
 
====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 oncer per day on days 1 & 8
 
 
'''28-day cycles'''
 
 
===References===
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/348293 PubMed]
 
# Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, Bowman D, Wolmark N, Wickerham DL, Kardinal CG et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990 Sep;8(9):1483-96. [http://jco.ascopubs.org/content/8/9/1483.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2202791 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. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. Philadelphia Bone Marrow Transplant Group. N Engl J Med. 2000 Apr 13;342(15):1069-76. [http://www.nejm.org/doi/full/10.1056/NEJM200004133421501 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10760307 PubMed]
 
# 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. [http://jco.ascopubs.org/content/19/4/943.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11181656 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. -->
 
# 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. [http://jco.ascopubs.org/content/29/34/4498.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22025143 PubMed]
 
 
==EC {{#subobject:b81844|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
EC: '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide
 
 
===Regimen {{#subobject:8466d6|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJM200103153441101 Slamon et al. 2001]
 
|style="background-color:#1a9850"|Phase III
 
|[[#ECH|ECH]]
 
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|[http://jco.ascopubs.org/content/23/33/8322.long Langley et al. 2005 (UKNCRI AB01)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#EP|EP]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====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 cycles'''
 
 
===References===
 
# Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. [http://www.nejm.org/doi/full/10.1056/NEJM200103153441101 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11248153 PubMed]
 
<!-- Presented at the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12-15, 2001. -->
 
# 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. [http://jco.ascopubs.org/content/23/33/8322.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16293863 PubMed]
 
 
==EP {{#subobject:e10567|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
EP: '''<u>E</u>'''pirubicin, '''<u>P</u>'''aclitaxel
 
 
===Regimen {{#subobject:f9fb8b|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/23/33/8322.long Langley et al. 2005 (UKNCRI AB01)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#EC_3|EC]]
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====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'''
 
 
===References===
 
<!-- Presented at the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12-15, 2001. -->
 
# 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. [http://jco.ascopubs.org/content/23/33/8322.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16293863 PubMed]
 
 
==FAC {{#subobject:b0cb|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
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 #1, 500/50/500 {{#subobject:ed75b0|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197911)44:5%3C1955::AID-CNCR2820440559%3E3.0.CO;2-P/abstract Hortobagyi et al. 1979]
 
|style="background-color:#1a9850"|Phase III
 
|FAC-BCG
 
|style="background-color:#d73027"|Inferior OS in responders
 
|-
 
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.11396/full Assikis et al. 2003]
 
|style="background-color:#1a9850"|Phase III
 
|[[Complex_multipart_regimens#Assikis_et_al._2003|See link]]
 
|[[Complex_multipart_regimens#Assikis_et_al._2003|See link]]
 
|-
 
|}
 
====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'''
 
 
''Treatment in '''Assikis et al. 2003''' followed by [[Breast_cancer_-_obsolete#MV|MV]].''
 
 
===Regimen #2 {{#subobject:b89f0f|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J/abstract Bull et al. 1978]
 
|style="background-color:#1a9850"|Phase III
 
|[[#CMF_2|CMF]]
 
|style="background-color:#d9ef8b"|Might have superior ORR
 
|-
 
|}
 
====Chemotherapy====
 
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
*[[Doxorubicin (Adriamycin)]] 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
 
 
'''28-day cycles'''
 
 
===References===
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/348293 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. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197911)44:5%3C1955::AID-CNCR2820440559%3E3.0.CO;2-P/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/387212 PubMed]
 
# Assikis V, Buzdar A, Yang Y, Smith T, Theriault R, Booser D, Valero V, Walters R, Singletary E, Ames F, Hortobagyi G. A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003 Jun 1;97(11):2716-23. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.11396/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12767083 PubMed]
 
 
==FEC {{#subobject:ed96e7|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
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 #1, "CEF21" {{#subobject:80e015|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.8.2213 Del Mastro et al. 2001]
 
|style="background-color:#1a9850"|Phase III
 
|HD-CEF14
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|}
 
====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 once on day 1
 
 
'''21-day cycle for 8 to 12 cycles'''
 
 
===Regimen #2 {{#subobject:830d7f|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/19/4/943.long Ackland et al. 2001 (HEPI 013)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#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'''
 
 
===Regimen #3, "FEC 100" {{#subobject:33c356|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://annonc.oxfordjournals.org/content/8/2/155.long Brufman et al. 1997 (HEPI 010)]
 
|style="background-color:#1a9850"|Phase III
 
|FEC 50
 
|style="background-color:#1a9850"|Superior ORR
 
|-
 
|}
 
====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 once on day 1
 
 
'''21-day cycle for 6 to 8 cycles'''
 
 
===Regimen #4, "FEC 50" {{#subobject:d92480|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://annonc.oxfordjournals.org/content/8/2/155.long Brufman et al. 1997 (HEPI 010)]
 
|style="background-color:#1a9850"|Phase III
 
|FEC 100
 
|style="background-color:#d73027"|Inferior ORR
 
|-
 
|}
 
====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 once on day 1
 
 
'''21-day cycle for 6 to 8 cycles'''
 
 
===References===
 
# Brufman G, Colajori E, Ghilezan N, Lassus M, Martoni A, Perevodchikova N, Tosello C, Viaro D, Zielinski C. 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. The Epirubicin High Dose (HEPI 010) Study Group. Ann Oncol. 1997 Feb;8(2):155-62. [http://annonc.oxfordjournals.org/content/8/2/155.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9093724 PubMed]
 
# 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. [http://jco.ascopubs.org/content/19/4/943.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. 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. [http://ascopubs.org/doi/full/10.1200/JCO.2001.19.8.2213 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11304774 PubMed]
 
 
==GT (Taxol) {{#subobject:1285e|Regimen=1}}==
 
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GT: '''<u>G</u>'''emcitabine, '''<u>T</u>'''axol (Paclitaxel)
 
 
===Regimen {{#subobject:5e5f66|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://jco.ascopubs.org/content/26/24/3950.long Albain et al. 2008]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel_monotherapy_3|Paclitaxel]]
 
|style="background-color:#91cf60"|Seems to have superior OS
 
|-
 
|}
 
====Chemotherapy====
 
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8; '''on day 1, administer after paclitaxel'''
 
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 
 
'''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. [http://jco.ascopubs.org/content/26/24/3950.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18711184 PubMed]
 
 
==Paclitaxel & Bevacizumab {{#subobject:1d634b|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
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|[[#top|back to top]]
 
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===Regimen {{#subobject:ba68f9|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa072113 Miller et al. 2007]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel_monotherapy_3|Paclitaxel]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30154-1/fulltext Zielinski et al. 2016 (TURANDOT)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Capecitabine_.26_Bevacizumab|Capecitabine & Bevacizumab]]
 
|style="background-color:#eeee00"|Non-inferior OS
 
|-
 
|[http://www.ejcancer.com/article/S0959-8049(16)32470-4/fulltext Miles et al. 2016 (MERiDiAN)]
 
|style="background-color:#1a9850"|Phase III
 
|[[#Paclitaxel_monotherapy_3|Paclitaxel]]
 
|style="background-color:#1a9850"|Superior PFS
 
|-
 
|}
 
====Chemotherapy====
 
*[[Paclitaxel (Taxol)]] 90 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 8, 15
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
 
'''28-day cycles'''
 
 
===References===
 
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa072113 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18160686 PubMed]
 
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30154-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27501767 PubMed]
 
# 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. [http://www.ejcancer.com/article/S0959-8049(16)32470-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27817944 PubMed]
 
 
==Paclitaxel, nanoparticle albumin-bound & Bevacizumab {{#subobject:17e71f|Regimen=1}}==
 
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===Example orders===
 
*[[Example orders for Paclitaxel, nanoparticle albumin-bound & Bevacizumab in breast cancer]]
 
 
===Regimen {{#subobject:8ded2a|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://meeting.ascopubs.org/cgi/content/abstract/26/15_suppl/1075 Danso et al. 2008]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
====Chemotherapy====
 
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 90 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 8, 15
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
 
'''28-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]
 
 
==Vinorelbine & Bevacizumab {{#subobject:f3046|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
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===Example orders===
 
*[[Example orders for Vinorelbine and Bevacizumab in breast cancer]]
 
 
===Regimen {{#subobject:82cbe7|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|[http://clincancerres.aacrjournals.org/content/14/23/7871.long Burstein et al. 2008]
 
|style="background-color:#91cf60"|Phase II
 
|-
 
|}
 
====Chemotherapy====
 
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per week
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once every other week
 
 
'''Given until progression of disease or unacceptable toxicity'''
 
 
===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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19047116 PubMed]
 
  
  
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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

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