Difference between revisions of "Complex multipart regimens"

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m
Line 1: Line 1:
−
The purpose of this page is to capture information about complex comparisons that is not easily conveyed on the treatment regimen pages. Many complex multipart RCTs are of the "Y-shaped" format "A followed by B1 versus B2" or "A1 versus A2 followed by B" and this can be captured on the treatment regimen pages. This page will convey information on more complicated designs, such as "A followed by B versus B followed by A" or "A followed by B versus C followed by D".
+
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Breast_cancer|main breast cancer page]] for current regimens.
  
−
{{TOC limit|limit=3}}
+
{| class="wikitable" style="float:right; margin-right: 5px;"
−
 
 
−
=[[Acute myeloid leukemia]]=
 
−
==COG AAML0531==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
−
|}
+
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
−
To be completed
+
|}
−
===References===
 
−
# Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. [https://ascopubs.org/doi/full/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25092781 PubMed]
 
  
−
==UK MRC AML12==
+
{{TOC limit|limit=3}}
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
To be completed
 
−
===References===
 
−
# Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood. 1999 Jun 15;93(12):4131-43. [http://www.bloodjournal.org/content/93/12/4131.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10361110 PubMed]
 
  
−
==UK MRC AML15==
+
=Neoadjuvant therapy=
 +
==CVAP {{#subobject:4a01b8|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
To be completed
+
CVAP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin),  '''<u>P</u>'''rednisolone
−
===References===
+
<br>VACP: '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisolone
−
# Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21172891 PubMed]
+
===Regimen {{#subobject:7b4b85|Variant=1}}===
−
 
+
{| class="wikitable" style="width: 50%; text-align:center;"  
−
=[[Acute promyelocytic leukemia]]=
+
!style="width: 25%"|Study
−
==C9710==
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://ascopubs.org/doi/full/10.1200/JCO.2002.20.6.1456 Smith et al. 2002]
−
|}
+
| style="background-color:#91cf61" |Non-randomized portion of RCT
−
''Note: this trial included a second randomization during the maintenance phase, which is not complex and is therefore not reported here.''
 
−
===Arm 1===
 
−
*[[Acute_promyelocytic_leukemia#ATRA.2C_Cytarabine.2C_Daunorubicin|ATRA, Cytarabine, Daunorubicin]], then [[Acute_promyelocytic_leukemia#ATRA_.26_Daunorubicin_2|ATRA & Daunorubicin]]
 
−
===Arm 2, with ATO3===
 
−
*[[Acute_promyelocytic_leukemia#ATRA.2C_Cytarabine.2C_Daunorubicin|ATRA, Cytarabine, Daunorubicin]], then [[Acute_promyelocytic_leukemia#Arsenic_trioxide_monotherapy_2|arsenic trioxide]], then [[Acute_promyelocytic_leukemia#ATRA_.26_Daunorubicin_2|ATRA & Daunorubicin]]
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Without ATO3
+
|[https://ascopubs.org/doi/full/10.1200/JCO.2004.05.207 Thomas E et al. 2004]
−
|style="background-color:#d73027"|Inferior EFS
+
| style="background-color:#91cf61" |Non-randomized portion of RCT
−
|-
 
−
|With ATO3
 
−
|style="background-color:#1a9850"|Superior EFS
 
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Vincristine (Oncovin)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
====Hormonotherapy====
 +
*[[Prednisolone (Millipred)]]
 +
====Subsequent treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
===References===
 
===References===
−
# Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. [http://www.bloodjournal.org/content/116/19/3751.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20705755 PubMed]
+
# Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, Ah-See AK, Eremin O, Walker LG, Sarkar TK, Eggleton SP, Ogston KN. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol. 2002 Mar 15;20(6):1456-66. [https://ascopubs.org/doi/full/10.1200/JCO.2002.20.6.1456 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11896092 PubMed]
 +
# Thomas E, Holmes FA, Smith TL, Buzdar AU, Frye DK, Fraschini G, Singletary SE, Theriault RL, McNeese MD, Ames F, Walters R, Hortobagyi GN. The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol. 2004 Jun 15;22(12):2294-302. [https://ascopubs.org/doi/full/10.1200/JCO.2004.05.207 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15197190 PubMed]
  
−
=[[Breast cancer]]=
+
==Epirubicin monotherapy {{#subobject:c54ed1|Regimen=1}}==
−
==ABCSG-8==
 
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
ABCSG-8: '''<u>A</u>'''ustrian '''<u>B</u>'''reast and '''<u>C</u>'''olorectal Cancer '''<u>S</u>'''tudy '''<u>G</u>'''roup '''<u>8</u>'''
+
===Regimen {{#subobject:21c010|Variant=1}}===
−
===Arm 1, monotherapy (Control)===
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5y
 
−
===Arm 2, sequential (Experimental)===
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 2y, then [[Breast_cancer,_ER-positive#Anastrozole_monotherapy_2|Anastrozole]] x 3y
 
−
===Comparative efficacy===
 
−
''Efficacy is based on the 2012 update.''
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Tamoxifen
+
|[https://erc.bioscientifica.com/view/journals/erc/12/2/0120383.xml Bottini et al. 2005]
−
|style="background-color:#fee08b"|Might have inferior RFS
+
| style="background-color:#1a9851" |Phase III (C)
−
|-
+
|Epirubicin & Tamoxifen
−
|Tamoxifen, then Anastrozole
+
| style="background-color:#ffffbf" |Seems not superior
−
|style="background-color:#d9ef8b"|Might have superior RFS
 
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Epirubicin (Ellence)]]
 +
====Subsequent treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
===References===
 
===References===
−
# Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H, Seifert M, Gademann G, Kaufmann M, Wolfgang J; ABCSG and the GABG. Switching of postmenopausal women with endocrine-responsiveearly breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005 Aug 6-12;366(9484):455-62. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)67059-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16084253 PubMed]
+
# Bottini A, Berruti A, Brizzi MP, Bersiga A, Generali D, Allevi G, Aguggini S, Bolsi G, Bonardi S, Tondelli B, Vana F, Tampellini M, Alquati P, Dogliotti L. Cytotoxic and antiproliferative activity of the single agent epirubicin versus epirubicin plus tamoxifen as primary chemotherapy in human breast cancer: a single-institution phase III trial. Endocr Relat Cancer. 2005 Jun;12(2):383-92. [https://erc.bioscientifica.com/view/journals/erc/12/2/0120383.xml link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15947110 PubMed]
−
<!-- Presented in poster format at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL. -->
 
−
## '''Update:''' Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, Filipcic L, Gnant M. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012 Mar 1;30(7):722-8. Epub 2012 Jan 23. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.8993 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22271481 PubMed]
 
  
−
==ACOSOG Z1041==
+
=Adjuvant therapy=
 +
==ACT {{#subobject:4a01b8|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Control)===
+
ACT: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''amoxifen
−
*[[Breast_cancer#FEC|FEC-75]] x 4, then [[Breast_cancer,_HER2-positive#TH_.28Taxol.29|TH (Taxol)]] x 12 wk, then [[surgery]]
+
===Regimen {{#subobject:7b4b85|Variant=1}}===
−
===Arm 2 (Experimental)===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
*[[Breast_cancer,_HER2-positive#TH_.28Taxol.29|TH (Taxol)]] x 12 wk, then [[Breast_cancer,_HER2-positive#FEC_.26_H|FEC & H]] x 4, then [[surgery]]
+
!style="width: 25%"|Study
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
!style="width: 25%"|Comparator
−
!'''Approach'''
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Sequential trastuzumab (C)
+
|rowspan=2|[https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.6.1005 Fisher et al. 1990 (NSABP B-16)]
−
|style="background-color:#ffffbf"|Seems not superior
+
|rowspan=2 style="background-color:#1a9851" |Phase III (E-esc)
 +
|1. [[#PFT|PFT]]
 +
| style="background-color:#d3d3d3" |Not reported
 
|-
 
|-
−
|Concurrent trastuzumab (E)
+
|2. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#91cf60" |Seems to have superior OS
 
|-
 
|-
−
|}
+
|[https://link.springer.com/article/10.1007%2Fs10147-013-0657-z Shien et al. 2014 (JCOG9401)]
−
===References===
+
|style="background-color:#1a9851" |Phase III (E-esc)
−
# Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig G, Royce M, McCall LM, Ewer MS, Hunt KK; American College of Surgeons Oncology Group investigators. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1317-25. Epub 2013 Nov 13. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70502-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176878/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24239210 PubMed]
+
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]]
−
 
+
| style="background-color:#91cf60" |Seems to have superior RFS
−
==ARNO 95==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143604/ Shien et al. 2014 (JCOG9404)]
−
|}
+
|style="background-color:#1a9851" |Phase III (E-de-esc)
−
===Arm 1, monotherapy (Control)===
+
|TUFT
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5y
+
| style="background-color:#ffffbf" |Seems not superior
−
===Arm 2, sequential (Experimental)===
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 2y, then [[Breast_cancer,_ER-positive#Anastrozole_monotherapy_2|Anastrozole]] x 3y
 
−
===Comparative efficacy===
 
−
''Efficacy is based on the 2007 update.''
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 50%"|'''Regimen'''
 
−
!style="width: 50%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Tamoxifen, then Anastrozole
 
−
|style="background-color:#91cf60"|Seems to have superior OS
 
−
|-
 
−
|Tamoxifen
 
−
|style="background-color:#fc8d59"|Seems to have inferior OS
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
====Hormonotherapy====
 +
*[[Tamoxifen (Nolvadex)]]
 
===References===
 
===References===
−
# Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H, Seifert M, Gademann G, Kaufmann M, Wolfgang J; ABCSG and the GABG. Switching of postmenopausal women with endocrine-responsiveearly breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005 Aug 6-12;366(9484):455-62. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)67059-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16084253 PubMed]
+
# '''NSABP B-16:''' Fisher B, Redmond C, Legault-Poisson S, Dimitrov NV, Brown AM, Wickerham DL, Wolmark N, Margolese RG, Bowman D, Glass AG, Kardinal CG, Robidoux A, Jochimsen P, Cronin W, Deutsch M, Fisher ER, Myers DB, Hoehn JL. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990 Jun;8(6):1005-18. [https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.6.1005 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2189950 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. -->
+
## '''Pooled update:''' Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. [https://ascopubs.org/doi/full/10.1200/JCO.2004.01.042 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15452182 PubMed]
−
## '''Update:''' 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]
+
# '''JCOG9401:''' Shien T, Iwata H, Aogi K, Fukutomi T, Inoue K, Kinoshita T, Takahashi M, Matsui A, Shibata T, Fukuda H. Tamoxifen versus tamoxifen plus doxorubicin and cyclophosphamide as adjuvant therapy for node-positive postmenopausal breast cancer: results of a Japan Clinical Oncology Group Study (JCOG9401). Int J Clin Oncol. 2014 Dec;19(6):982-8. Epub 2014 Jan 7. [https://link.springer.com/article/10.1007%2Fs10147-013-0657-z link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24395447 PubMed]
 +
# '''JCOG9404:''' Shien T, Iwata H, Fukutomi T, Inoue K, Aogi K, Kinoshita T, Ando J, Takashima S, Nakamura K, Shibata T, Fukuda H. Tamoxifen plus tegafur-uracil (TUFT) versus tamoxifen plus Adriamycin (doxorubicin) and cyclophosphamide (ACT) as adjuvant therapy to treat node-positive premenopausal breast cancer (PreMBC): results of Japan Clinical Oncology Group Study 9404. Cancer Chemother Pharmacol. 2014 Sep;74(3):603-9. Epub 2014 Jul 24. [https://link.springer.com/article/10.1007%2Fs00280-014-2545-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143604/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25055938 PubMed]
  
−
==Assikis et al. 2003==
+
==AVCF {{#subobject:4a0878|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1===
+
AVCF: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil
−
*[[Breast_cancer#FAC|FAC]], then [[Breast_cancer_-_historical#MV|MV]]
+
===Regimen {{#subobject:7b4c73|Variant=1}}===
−
===Arm 2===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]]
+
!style="width: 25%"|Study
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
!style="width: 25%"|Comparator
−
!'''Regimen'''
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|FAC, then MV
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.4.1136 Misset et al. 1996 (OncoFrance)]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#1a9851" |Phase III (E-RT-esc)
−
|-
+
|[[Breast_cancer#CMF|CMF]]
−
|Tamoxifen
+
| style="background-color:#1a9850" |Superior OS
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Vincristine (Oncovin)]]
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Fluorouracil (5-FU)]]
 
===References===
 
===References===
−
# 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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.11396/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12767083 PubMed]
+
# '''OncoFrance:''' Misset JL, di Palma M, Delgado M, Plagne R, Chollet P, Fumoleau P, Le Mevel B, Belpomme D, Guerrin J, Fargeot P, Metz R, Ithzaki M, Hill C, Mathé G. Adjuvant treatment of node-positive breast cancer with cyclophosphamide, doxorubicin, fluorouracil, and vincristine versus cyclophosphamide, methotrexate, and fluorouracil: final report after a 16-year median follow-up duration. J Clin Oncol. 1996 Apr;14(4):1136-45. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.4.1136 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8648368 PubMed]
  
−
==BCIRG-005==
+
==AV-CMF {{#subobject:4a3928|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, sequential (Experimental)===
+
AV-CMF: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''inblastine, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
−
*[[Breast_cancer#AC|AC]], then [[Breast_cancer#Docetaxel_monotherapy_2|T]]
+
===Regimen {{#subobject:7bcju3|Variant=1}}===
−
===Arm 2, concurrent (Control)===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
*[[Breast_cancer#TAC_.28Taxotere.29|TAC]]
+
!style="width: 25%"|Study
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
!style="width: 25%"|Comparator
−
!'''Schedule'''
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Sequential (AC, then T)
+
|[https://www.karger.com/Article/PDF/69831 Ploner et al. 2003 (ABCSG 3)]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#1a9851" |Randomized (E-RT-esc)
−
|-
+
|[[Breast_cancer#CMF|CMF]]
−
|Concurrent (TAC)
+
| style="background-color:#ffffbf" |Seems not superior
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Vinblastine (Velban)]]
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 
===References===
 
===References===
−
# 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] [https://www.ncbi.nlm.nih.gov/pubmed/21911726 PubMed]
+
# '''ABCSG 3:''' Ploner F, Jakesz R, Hausmaninger H, Kolb R, Stierer M, Fridrik M, Steindorfer P, Gnant M, Haider K, Mlineritsch B, Tschurtschenthaler G, Steger G, Seifert M, Kubista E, Samonigg H; Austrian Breast And Colorectal Cancer Study Group. Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive, hormone receptor-negative breast cancer patients. Onkologie. 2003 Apr;26(2):115-9. [https://www.karger.com/Article/PDF/69831 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12771518 PubMed]
  
−
==BCIRG 006==
+
==CAMFP {{#subobject:4a01b8|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, sequential without trastuzumab===
+
CAMFP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
−
*[[Breast_cancer#AC|AC]], then [[Breast_cancer#Docetaxel_monotherapy_2|T]]
+
===Regimen {{#subobject:7b4b85|Variant=1}}===
−
===Arm 2, sequential with trastuzumab===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
*[[Breast_cancer#AC|AC]], then [[Breast_cancer,_HER2-positive#TH_.28Taxotere.29_2|TH]]
+
!style="width: 25%"|Study
−
===Arm 3, concurrent with trastuzumab===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
*[[Breast_cancer,_HER2-positive#TCH_.28Taxotere.2C_Carboplatin.29|TCH]]
+
!style="width: 25%"|Comparator
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
*Analyzed using a step-down design
 
−
====Comparison 1====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Trastuzumab-containing regimens vs. AC, then T'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|AC, then TH
 
−
|style="background-color:#1a9850"|Superior OS
 
 
|-
 
|-
−
|TCH
+
|[https://www.nejm.org/doi/full/10.1056/NEJM199605233342102 Recht et al. 1996]
−
|style="background-color:#91cf60"|Seems to have superior OS
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
−
|-
+
|[[Complex_multipart_regimens#Recht_et_al._1996|See link]]
−
|}
+
|[[Complex_multipart_regimens#Recht_et_al._1996|See link]]
−
====Comparison 2====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Trastuzumab-containing regimens'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|AC, then TH
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|TCH
 
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
 +
''Note: this was a trial examining sequencing of chemotherapy and radiotherapy; see text for efficacy details.''
 +
====Preceding treatment====
 +
*[[Surgery#Lumpectomy|Lumpectomy]]
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 +
====Hormonotherapy====
 +
*[[Prednisone (Sterapred)]]
 +
 +
'''21-day cycle for 4 cycles'''
 +
 
===References===
 
===References===
−
# 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. [https://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]
+
# Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, Shulman LN, Harris JR. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996 May 23;334(21):1356-61. [https://www.nejm.org/doi/full/10.1056/NEJM199605233342102 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8614420 PubMed]
  
−
==BIG 1-98==
+
==CEF/CMF {{#subobject:682333|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, monotherapy===
+
CEF/CMF: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>F</u>'''luorouracil alternating with '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
−
*[[Breast_cancer,_ER-positive#Letrozole_monotherapy|Letrozole]] x 5y
+
===Regimen {{#subobject:3d1971|Variant=1}}===
−
===Arm 2, sequential===
 
−
*[[Breast_cancer,_ER-positive#Letrozole_monotherapy|Letrozole]] x 2y, then [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 3y
 
−
===Arm 3, monotherapy===
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5y
 
−
===Arm 4, sequential===
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 2y, then [[Breast_cancer,_ER-positive#Letrozole_monotherapy|Letrozole]] x 3y
 
−
===Comparative efficacy===
 
−
*Analyzed by several methods; efficacy here is based on the 2011 update.
 
−
====Comparison 1====
 
−
''Reported efficacy is based on the 2018 update.''
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Monotherapy'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Letrozole
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202939/ Bedognetti et al. 2011]
−
| style="background-color:#d9ef8b" |Might have superior OS
+
| style="background-color:#1a9851" |Phase III (C)
−
|-
+
|CEFT/CMFT
−
|Tamoxifen
+
| style="background-color:#ffffbf" |Seems not superior
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|}
 
−
====Comparison 2====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Sequential therapies'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Letrozole, then Tamoxifen
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|Tamoxifen, then Letrozole
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|}
 
−
====Comparison 3====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Letrozole-containing therapies'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Letrozole
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|Letrozole, then Tamoxifen
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|Tamoxifen, then Letrozole
 
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy, CEF portion====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Epirubicin (Ellence)]]
 +
*[[Fluorouracil (5-FU)]]
 +
====Chemotherapy, CMF portion====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 
===References===
 
===References===
−
# 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; Breast International Group (BIG) 1-98 Collaborative Group. 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 ]. [https://www.nejm.org/doi/full/10.1056/NEJMoa052258 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16382061 PubMed]
+
# Bedognetti D, Sertoli MR, Pronzato P, Del Mastro L, Venturini M, Taveggia P, Zanardi E, Siffredi G, Pastorino S, Queirolo P, Gardin G, Wang E, Monzeglio C, Boccardo F, Bruzzi P. Concurrent vs sequential adjuvant chemotherapy and hormone therapy in breast cancer: a multicenter randomized phase III trial. J Natl Cancer Inst. 2011 Oct 19;103(20):1529-39. Epub 2011 Sep 15. [https://academic.oup.com/jnci/article/103/20/1529/905862 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202939/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21921285 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. [https://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. [https://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]
 
−
## '''Update:''' Ruhstaller T, Giobbie-Hurder A, Colleoni M, Jensen MB, Ejlertsen B, de Azambuja E, Neven P, Láng I, Jakobsen EH, Gladieff L, Bonnefoi H, Harvey VJ, Spazzapan S, Tondini C, Del Mastro L, Veyret C, Simoncini E, Gianni L, Rochlitz C, Kralidis E, Zaman K, Jassem J, Piccart-Gebhart M, Di Leo A, Gelber RD, Coates AS, Goldhirsch A, Thürlimann B, Regan MM; members of the BIG 1-98 Collaborative Group and the International Breast Cancer Study Group. Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor-Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial. J Clin Oncol. 2018 Nov 26:JCO1800440. [Epub ahead of print] [https://ascopubs.org/doi/full/10.1200/JCO.18.00440 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30475668 PubMed]
 
  
−
==BIG 02-98==
+
==CFP {{#subobject:b514cd|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, sequential control===
+
CFP: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
−
*Surgery, then [[Breast_cancer#Doxorubicin_monotherapy|A]] x 4, then [[Breast_cancer#CMF|CMF]] x 3
+
===Regimen {{#subobject:3b8f7d|Variant=1}}===
−
===Arm 2, concurrent control===
 
−
*Surgery, then [[Breast_cancer#AC_2|AC]] x 4, then [[Breast_cancer#CMF|CMF]] x 3
 
−
===Arm 3, sequential experimental===
 
−
*Surgery, then [[Breast_cancer#Doxorubicin_monotherapy|A]] x 4, [[Breast_cancer#Docetaxel_monotherapy_2|D]] x 3, then [[Breast_cancer#CMF|CMF]] x 3
 
−
===Arm 4, concurrent experimental===
 
−
*Surgery, then AT x 4, then [[Breast_cancer#CMF|CMF]] x 3
 
−
 
 
−
===Comparative efficacy===
 
−
''This trial was analyzed with a 2 x 2 factorial design. Reported efficacy is based on the 2015 update.''
 
−
====Comparison 1 - addition of docetaxel====
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
|'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Non-docetaxel-containing (C)
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(78)90678-5/fulltext Ahmann et al. 1978]
−
|style="background-color:#ffffbf"|Seems not superior (*)
+
|style="background-color:#1a9851" |Phase III (E-esc)
 +
|[[#Melphalan_monotherapy|Melphalan]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 
|-
 
|-
−
|Docetaxel containing (E)
+
|rowspan=2|[https://jamanetwork.com/journals/jama/article-abstract/370748 Caprini et al. 1980]
−
|style="background-color:#ffffbf"|Seems not superior (*)
+
|rowspan=2 style="background-color:#1a9851" |Phase III (E-esc)
 +
|1. [[#Melphalan_monotherapy|Melphalan]]
 +
| style="background-color:#91cf60" |Seems to have superior DFS
 
|-
 
|-
−
|}
+
|2. CFP & BCG
−
====Comparison 2 - sequencing====
+
| style="background-color:#ffffbf" |Seems not superior
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
|'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Sequential
 
−
|style="background-color:#ffffbf"|Seems not superior (*)
 
−
|-
 
−
|Concurrent
 
−
|style="background-color:#ffffbf"|Seems not superior (*)
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Fluorouracil (5-FU)]]
 +
====Hormonotherapy====
 +
*[[Prednisone (Sterapred)]]
 
===References===
 
===References===
−
# Francis P, Crown J, Di Leo A, Buyse M, Balil A, Andersson M, Nordenskjöld B, Lang I, Jakesz R, Vorobiof D, Gutiérrez J, van Hazel G, Dolci S, Jamin S, Bendahmane B, Gelber RD, Goldhirsch A, Castiglione-Gertsch M, Piccart-Gebhart M; BIG 02-98 Collaborative Group. Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial. J Natl Cancer Inst. 2008 Jan 16;100(2):121-33. Epub 2008 Jan 8. Erratum in: J Natl Cancer Inst. 2008 Nov 19;100(22):1655. [https://academic.oup.com/jnci/article/100/2/121/1130035 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18182617 PubMed]
+
# Ahmann DL, Scanlon PW, Bisel HF, Edmonson JH, Frytak S, Payne WS, O'Fallon JR, Hahn RG, Ingle JN, O'Connell MJ, Rubin J. Repeated adjuvant chemotherapy with phenylalanine mustard or 5-fluorouracil, cyclophosphamide, and prednisone with or without radiation, after mastectomy for breast cancer. Lancet. 1978 Apr 29;1(8070):893-6. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(78)90678-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/76842 PubMed]
−
## '''Update:''' Oakman C, Francis PA, Crown J, Quinaux E, Buyse M, De Azambuja E, Margeli Vila M, Andersson M, Nordenskjöld B, Jakesz R, Thürlimann B, Gutiérrez J, Harvey V, Punzalan L, Dell'orto P, Larsimont D, Steinberg I, Gelber RD, Piccart-Gebhart M, Viale G, Di Leo A. Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer--8-year results of the Breast International Group 02-98 phase III trial. Ann Oncol. 2013 May;24(5):1203-11. Epub 2013 Jan 4. [https://academic.oup.com/annonc/article/24/5/1203/215838 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23293111 PubMed]
+
# Caprini JA, Oviedo MA, Cunningham MP, Cohen E, Trueheart RS, Khandekar JD, Scanlon EF. Adjuvant chemotherapy for stage II and III breast carcinoma. JAMA. 1980 Jul 18;244(3):243-6. [https://jamanetwork.com/journals/jama/article-abstract/370748 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6991733 PubMed]
−
## '''Update:''' Sonnenblick A, Francis PA, Azim HA Jr, de Azambuja E, Nordenskjöld B, Gutiérez J, Quinaux E, Mastropasqua MG, Ameye L, Anderson M, Lluch A, Gnant M, Goldhirsch A, Di Leo A, Barnadas A, Cortes-Funes H, Piccart M, Crown J. Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer. Eur J Cancer. 2015 Aug;51(12):1481-9. Epub 2015 Jun 11. [https://www.ejcancer.com/article/S0959-8049(15)00285-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26074397 PubMed]
 
  
−
==BR9601==
+
==CFP & Oophorectomy {{#subobject:ba429d|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Control)===
+
CFP & Oophorectomy: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone & Bilateral Oophorectomy
−
*[[Breast_cancer#CMF|CMF]] x 8
+
===Regimen {{#subobject:26519a|Variant=1}}===
−
===Arm 2 (Experimental)===
 
−
*[[Breast_cancer#EC_2|EC]] x 4, then [[Breast_cancer#CMF|CMF]] x 4
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|CMF x 8
+
|[https://www.nejm.org/doi/full/10.1056/NEJM197708182970704 Ahmann et al. 1977]
−
|style="background-color:#d73027"|Inferior OS
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
|-
+
|[[#Oophorectomy|Oophorectomy]]
−
|EC x 4, then CMF x 4
+
| style="background-color:#91cf60" |Seems to have superior PFS
−
|style="background-color:#1a9850"|Superior OS
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Fluorouracil (5-FU)]]
 +
====Hormonotherapy====
 +
*[[Prednisone (Sterapred)]]
 +
*[[Endocrine_ablation_surgery#Bilateral_oophorectomy|Bilateral oophorectomy]]
 +
 
===References===
 
===References===
−
<!-- no pre-pub disclosed -->
+
# Ahmann DL, O'Connell MJ, Hahn RG, Bisel HF, Lee RA, Edmonson JH. An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advanced breast cancer undergoing oophorectomy. N Engl J Med. 1977 Aug 18;297(7):356-60. [https://www.nejm.org/doi/full/10.1056/NEJM197708182970704 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/876327 PubMed]
−
# Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. [https://www.nejm.org/doi/full/10.1056/NEJMoa052084 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17079759 PubMed]
 
  
−
==Buzdar et al. 2005==
+
==CMFL {{#subobject:1abd14|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Control)===
+
CMFL: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin (Folinic acid)
−
*[[Breast_cancer#Paclitaxel_monotherapy|T]] x 4, then [[Breast_cancer#FEC|FEC]] x 4, then [[surgery]]
+
===Regimen {{#subobject:3dbcd1|Variant=1}}===
−
===Arm 2 (Experimental)===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
*[[Breast_cancer,_HER2-positive#TH_.28Taxol.29|TH]] x 4, then [[Breast_cancer,_HER2-positive#FEC_.26_H|FEC & H]] x 4, then [[surgery]]
+
!style="width: 25%"|Study
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
!style="width: 25%"|Comparator
−
!'''Regimen'''
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|T, then FEC
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200804 Goldhirsch et al. 1989 (LCBS V)]
−
|style="background-color:#fc8d59"|Seems to have inferior pCR rate
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
|-
+
|[[#Observation|No further treatment]]
−
|TH, then FEC & H
+
| style="background-color:#91cf60" |Seems to have superior DFS
−
|style="background-color:#91cf60"|Seems to have superior pCR rate
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Mastectomy|Mastectomy]]
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 +
*[[Folinic acid (Leucovorin)]]
 +
 +
'''8-day course'''
 +
 
===References===
 
===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]
+
# '''LCBS V:''' Goldhirsch A, Gelber RD; Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med. 1989 Feb 23;320(8):491-6. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200804 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2644533 PubMed]
  
−
==CALGB 9741==
+
==CMFP {{#subobject:527931|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
''Note: what is referred to in this study as concurrent is in fact the same regimen that is referred to as sequential in other studies. The taxane studied in this trial was paclitaxel.''
+
CMFP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
−
===Arm 1, sequential===
+
===Regimen {{#subobject:3feec0|Variant=1}}===
−
*A x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T q3wk]] x 4, then C x 4
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
===Arm 2, dose-dense sequential===
+
!style="width: 25%"|Study
−
*[[Breast_cancer#ddA|ddA]] x 4, then [[Breast_cancer#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|ddT]] x 4, then [[Breast_cancer#ddC|ddC]] x 4
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
===Arm 3, "concurrent"===
+
!style="width: 25%"|Comparator
−
*[[Breast_cancer#AC_2|AC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T q3wk]] x 4
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
===Arm 4, dose-dense "concurrent"===
 
−
*[[Breast_cancer#ddAC_2|ddAC]] x 4, then [[Breast_cancer#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|ddT]] x 4
 
−
===Comparative efficacy===
 
−
*Analyzed using a 2 x 2 factorial design
 
−
====Comparison 1====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
|'''Dose density'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Dose-dense (q2wk)
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198809153191104 Goldhirsch et al. 1988 (IBCSG V)]
−
|style="background-color:#91cf60"|Seems to have superior OS
+
| style="background-color:#1a9851" |Phase III (C)
 +
|[[#CMFL|CMFL]] x 1
 +
| style="background-color:#91cf60" |Seems to have superior OS
 
|-
 
|-
−
|Standard (q3wk)
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200803 Mansour et al. 1989 (INT-0011)]
−
|style="background-color:#fc8d59"|Seems to have inferior OS
+
| style="background-color:#1a9851" |Phase III (E-esc)
 +
|[[#Observation|No further treatment]]
 +
| style="background-color:#1a9850" |Superior DFS
 
|-
 
|-
−
|}
+
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q/abstract Tormey et al. 1990 (ECOG E5177)]
−
====Comparison 2====
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
{| class="wikitable" style="width: 100%; text-align:center;"
+
|1. [[Breast_cancer#CMF|CMF]]<br> 2. [[#CMFPT|CMFPT]]
−
|'''Schedule'''
+
| style="background-color:#ffffbf" |Seems not superior
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Concurrent
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|Sequential
 
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Modified_radical_mastectomy|Modified radical mastectomy]] or [[Surgery#Mastectomy|total mastectomy]] with [[Surgery#Axillary_lymph_node_dissection|low axillary-node dissection]]
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 +
====Hormonotherapy====
 +
*[[Prednisone (Sterapred)]]
 +
 +
'''28-day cycle for 6 to 12 cycles'''
 +
 
===References===
 
===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]
+
# '''IBCSG V:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Combination adjuvant chemotherapy for node-positive breast cancer: inadequacy of a single perioperative cycle. N Engl J Med. 1988 Sep 15;319(11):677-83. [https://www.nejm.org/doi/full/10.1056/NEJM198809153191104 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2901037 PubMed]
 +
# '''ECOG E1180:''' Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med. 1989 Feb 23;320(8):485-90. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200803 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2915651 PubMed]
 +
## '''Update:''' Mansour EG, Eudey L, Tormey DC, Shatila AH, Osborne CK, Gilchrist KW, Cooper MR, Falkson G. Chemotherapy versus observation in high-risk node-negative breast cancer patients. J Natl Cancer Inst Monogr. 1992;(11):97-104. [https://www.ncbi.nlm.nih.gov/pubmed/1627437 PubMed]
 +
# '''ECOG E5177:''' Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. [https://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]
  
−
==DBCG 82b==
+
==CMFPT {{#subobject:204d9d|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Experimental)===
+
CMFPT: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone, '''<u>T</u>'''amoxifen
−
*[[Mastectomy]], then [[Breast_cancer#CMF|CMF]] x 1, then radiotherapy, then [[Breast_cancer#CMF|CMF]] x 7
+
===Regimen {{#subobject:3a762a|Variant=1}}===
−
===Arm 2 (Control)===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
*[[Mastectomy]], then [[Breast_cancer#CMF|CMF]] x 9
+
!style="width: 25%"|Study
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
!style="width: 25%"|Comparator
−
!'''Regimen'''
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|With RT
+
|rowspan = 2|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS III)]
−
| style="background-color:#1a9850" |Superior OS
+
|rowspan = 2 style="background-color:#1a9851" |Phase III (E-esc)
 +
|1. [[#Observation|Observation]]
 +
| style="background-color:#1a9850" |Superior DFS
 
|-
 
|-
−
|Without RT
+
|2. [[#PT|PT]]
−
| style="background-color:#d73027" |Inferior OS
+
| style="background-color:#91cf60" |Seems to have superior DFS
 
|-
 
|-
−
|}
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198809153191104 Goldhirsch et al. 1988 (IBCSG V)]
−
===References===
+
| style="background-color:#1a9851" |Phase III (C)
−
# Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy: Danish Breast Cancer Cooperative Group 82b trial. N Engl J Med. 1997 Oct 2;337(14):949-55. [https://www.nejm.org/doi/full/10.1056/NEJM199710023371401 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9395428 PubMed]
+
|[[#CMFL|CMFL]] x 1
−
 
+
| style="background-color:#91cf60" |Seems to have superior OS
−
==DBCG 07-READ==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q/abstract Tormey et al. 1990 (ECOG E5177)]
−
|}
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
===Arm 1===
+
|1. [[Breast_cancer#CMF|CMF]]<br> 2. CMFP
−
*[[Surgery]], then [[Breast_cancer#TC|DC]] x 6
+
| style="background-color:#ffffbf" |Seems not superior
−
===Arm 2, "EC-D"===
 
−
*[[Surgery]], then [[Breast_cancer#EC_2|EC]] x 3, then [[Breast_cancer#Docetaxel_monotherapy_2|D]] x 3
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|DC x 6
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.4.599 Falkson et al. 1990]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#1a9851" |Phase III (C)
−
|-
+
|CMFPT x 4
−
|EC x 3, then D x 3
+
| style="background-color:#ffffbf" |Seems not superior
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Modified_radical_mastectomy|Modified radical mastectomy]] or [[Surgery#Mastectomy|total mastectomy]] with [[Surgery#Axillary_lymph_node_dissection|low axillary-node dissection]]
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 +
====Hormonotherapy====
 +
*[[Prednisone (Sterapred)]]
 +
*[[Tamoxifen (Nolvadex)]]
 +
 +
'''28-day cycle for 6 to 12 cycles'''
 +
 
===References===
 
===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. [https://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]
+
# '''LBCS III/IV:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. [https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6144974 PubMed]
 +
# '''IBCSG V:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Combination adjuvant chemotherapy for node-positive breast cancer: inadequacy of a single perioperative cycle. N Engl J Med. 1988 Sep 15;319(11):677-83. [https://www.nejm.org/doi/full/10.1056/NEJM198809153191104 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2901037 PubMed]
 +
# '''ECOG E5177:''' Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. [https://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]
 +
# Falkson HC, Gray R, Wolberg WH, Gillchrist KW, Harris JE, Tormey DC, Falkson G. Adjuvant trial of 12 cycles of CMFPT followed by observation or continuous tamoxifen versus four cycles of CMFPT in postmenopausal women with breast cancer: an Eastern Cooperative Oncology Group phase III study. J Clin Oncol. 1990 Apr;8(4):599-607. Erratum in: J Clin Oncol 1990 Sep;8(9):1603. [https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.4.599 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2179477 PubMed]
  
−
==DEVA==
+
==CMFT {{#subobject:204b9d|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Control)===
+
CMFT: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>T</u>'''amoxifen
−
*[[Surgery]], then [[Breast_cancer#Epirubicin_monotherapy|Epirubicin]] x 6
+
===Regimen {{#subobject:3agt2a|Variant=1}}===
−
===Arm 2 (Experimental)===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
*[[Surgery]], then [[Breast_cancer#Epirubicin_monotherapy|Epirubicin]] x 3, then [[Breast_cancer#Docetaxel_monotherapy_2|Docetaxel]] x 3
+
!style="width: 25%"|Study
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
!style="width: 25%"|Comparator
−
!'''Regimen'''
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Epirubicin
+
|[https://www.surgjournal.com/article/0039-6060(80)90244-5/fulltext Hubay et al. 1980]
−
|style="background-color:#d73027"|Inferior DFS
+
| style="background-color:#1a9851" |Randomized (E-RT-esc)
−
|-
+
|CMF
−
|Epirubicin, then Docetaxel
+
| style="background-color:#91cf60" |Seems to have superior RFS
−
|style="background-color:#1a9850"|Superior DFS
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Modified_radical_mastectomy|Modified radical mastectomy]] or [[Surgery#Mastectomy|total mastectomy]] with [[Surgery#Axillary_lymph_node_dissection|low axillary-node dissection]]
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 +
====Hormonotherapy====
 +
*[[Tamoxifen (Nolvadex)]]
 +
 
===References===
 
===References===
−
<!-- Presented at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL. -->
+
# Hubay CA, Pearson OH, Marshall JS, Rhodes RS, Debanne SM, Mansour EG, Hermann RE, Jones JC, Flynn WJ, Eckert C, McGuire WL. Antiestrogen, cytotoxic chemotherapy, and bacillus Calmette-Guerin vaccination in stage II breast cancer: a preliminary report. Surgery. 1980 May;87(5):494-501. [https://www.surgjournal.com/article/0039-6060(80)90244-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7368100 PubMed]
−
# Coombes RC, Bliss JM, Espie M, Erdkamp F, Wals J, Tres A, Marty M, Coleman RE, Tubiana-Mathieu N, den Boer MO, Wardley A, Kilburn LS, Cooper D, Thomas MW, Reise JA, Wilkinson K, Hupperets P. Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with  node-positive breast cancer. J Clin Oncol. 2011 Aug 20;29(24):3247-54. Epub 2011 Jul 18. [https://ascopubs.org/doi/full/10.1200/JCO.2010.32.7254 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21768453 PubMed]
+
## '''Update:''' Hubay CA, Pearson OH, Marshall JS, Rhodes RS, DeBanne SM, Rosenblatt J, Mansour EG, Hermann RE, Jones JC, Flynn WJ, Eckert C, McGuire WL. Adjuvant chemotherapy, antiestrogen therapy and immunotherapy for stage II breast cancer: 45-month follow-up of a prospective, randomized clinical trial. Cancer. 1980 Dec 15;46(12 Suppl):2805-8. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19801215)46:12%2B%3C2805::AID-CNCR2820461413%3E3.0.CO;2-H link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7004624 PubMed]
  
−
==ECOG E5103==
+
==CMFVP {{#subobject:ae7a82|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm A (Control)===
+
CMFVP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
−
*[[Surgery]], then [[Breast_cancer#AC_2|AC]] x 4 or [[Breast_cancer#ddAC_2|ddAC]] x 4, then [[Breast_cancer#Paclitaxel_monotherapy.2C_weekly_2|wP]] x 12
+
===Regimen {{#subobject:538cb7|Variant=1}}===
−
===Arm B (Experimental)===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
*[[Surgery]], then AC-Bev x 4 or ddAC-Bev x 4, then wP-Bev
+
!style="width: 25%"|Study
−
===Arm C (Experimental)===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
*[[Surgery]], then AC-Bev x 4 or ddAC-Bev x 4, then wP-Bev, then [[Breast_cancer#Bevacizumab_monotherapy|bevacizumab]] x 10
+
!style="width: 25%"|Comparator
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Backbone'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|No bevacizumab
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197607)38:1%3C13::AID-CNCR2820380104%3E3.0.CO;2-5 Hoogstraten et al. 1976]
−
| style="background-color:#ffffbf" |Seems not superior
+
|style="background-color:#1a9851" |Phase III (E-esc)
 +
|[[Breast_cancer#Doxorubicin_monotherapy_3|Doxorubicin]]
 +
| style="background-color:#91cf60" |Seems to have superior ORR
 
|-
 
|-
−
|With bevacizumab
+
|[https://www.sciencedirect.com/science/article/pii/0014296480900377 Carmo-Pereira et al. 1980]
−
| style="background-color:#ffffbf" |Seems not superior
+
|style="background-color:#1a9851" |Phase III (E-esc)
 +
|5-FU
 +
| style="background-color:#1a9850" |Superior OS
 
|-
 
|-
−
|}
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19820801)50:3%3C423::AID-CNCR2820500307%3E3.0.CO;2-O Glucksberg et al. 1982 (SWOG S7436)]
−
===References===
+
|style="background-color:#1a9851" |Phase III (E-esc)
−
# Miller KD, O'Neill A, Gradishar W, Hobday TJ, Goldstein LJ, Mayer IA, Bloom S, Brufsky AM, Tevaarwerk AJ, Sparano JA, Le-Lindqwister NA, Hendricks CB, Northfelt DW, Dang CT, Sledge GW Jr. Double-blind phase III trial of adjuvant chemotherapy with and without bevacizumab in patients with lymph node-positive and high-risk lymph node-negative breast cancer (E5103). J Clin Oncol. 2018 Sep 1;36(25):2621-2629. Epub 2018 Jul 24. [https://ascopubs.org/doi/full/10.1200/JCO.2018.79.2028 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30040523 PubMed]
+
|[[#Melphalan_monotherapy|Melphalan]]
−
 
+
| style="background-color:#1a9850" |Superior OS
−
==ECTO==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|rowspan=2|[https://ascopubs.org/doi/abs/10.1200/JCO.1983.1.2.138 Tormey et al. 1983a]
−
|}
+
|rowspan=2 style="background-color:#1a9851" |Phase III (E-esc)
−
===Arm A (Control)===
+
|[[Breast_cancer#CMF|CMF]]
−
*[[Surgery]], then [[Breast_cancer#Doxorubicin_monotherapy|A]] x 4, then [[Breast_cancer#CMF|CMF]] x 4
+
| style="background-color:#1a9850" |Superior DFS
−
===Arm B (Experimental)===
 
−
*[[Surgery]], then [[Breast_cancer#AT_.28Taxol.29|AT (Taxol)]] x 4, then [[Breast_cancer#CMF|CMF]] x 4
 
−
===Arm C (Experimental)===
 
−
*AT (Taxol) x 4, then CMF x 4, then [[surgery]]
 
−
===Comparative efficacy===
 
−
====Comparison 1====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Paclitaxel'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Included
+
|CMF-MER
−
| style="background-color:#91cf60" |Seems to have superior RFS
+
| style="background-color:#d3d3d3" |Not reported
 
|-
 
|-
−
|Not included
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1993.11.9.1710 Rivkin et al. 1993 (SWOG S7827<sub>ER-</sub>)]
−
| style="background-color:#fc8d59" |Seems to have inferior RFS
+
|style="background-color:#1a9851" |Phase III (C)
 +
|CMFVP x 2 y
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
−
|}
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1995.13.4.831 Budd et al. 1995 (SWOG S8313)]
−
====Comparison 2====
+
|style="background-color:#1a9851" |Phase III (C)
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
|FAC-M
−
!'''Timing'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Adjuvant AT-CMF
 
 
| style="background-color:#ffffbf" |Seems not superior
 
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
−
|Neoadjuvant AT-CMF
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.1.46 Rivkin et al. 1996 (SWOG S7821)]
 +
|style="background-color:#1a9851" |Phase III (C)
 +
|CMFVP & Oophorectomy
 
| style="background-color:#ffffbf" |Seems not superior
 
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 +
*[[Vincristine (Oncovin)]]
 +
====Hormonotherapy====
 +
*[[Prednisone (Sterapred)]]
 +
 
===References===
 
===References===
−
# Gianni L, Baselga J, Eiermann W, Porta VG, Semiglazov V, Lluch A, Zambetti M, Sabadell D, Raab G, Cussac AL, Bozhok A, Martinez-Agulló A, Greco M, Byakhov M, Lopez JJ, Mansutti M, Valagussa P, Bonadonna G. Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol. 2009 May 20;27(15):2474-81. Epub 2009 Mar 30. [https://ascopubs.org/doi/full/10.1200/JCO.2008.19.2567 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19332727 PubMed]
+
# Hoogstraten B, George SL, Samal B, Rivkin SE, Costanzi JJ, Bonnet JD, Thigpen T, Braine H. Combination chemotherapy and adriamycin in patients with advanced breast cancer: a Southwest Oncology Group study. Cancer. 1976 Jul;38(1):13-20. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197607)38:1%3C13::AID-CNCR2820380104%3E3.0.CO;2-5 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/947510 PubMed]
 +
# Carmo-Pereira J, Costa FO, Henriques E. Single-drug vs combination cytotoxic chemotherapy in advanced breast cancer: a randomized study. Eur J Cancer. 1980 Dec;16(12):1621-5. [https://www.sciencedirect.com/science/article/pii/0014296480900377 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/7014228 PubMed]
 +
# '''SWOG S7436:''' Glucksberg H, Rivkin SE, Rasmussen S, Tranum B, Gad-el-Mawla N, Costanzi J, Hoogstraten B, Athens J, Maloney T, McCracken J, Vaughn C. Combination chemotherapy (CMFVP) versus L-phenylalanine mustard (L-PAM) for operable breast cancer with positive axillary nodes: a Southwest Oncology Group Study. Cancer. 1982 Aug 1;50(3):423-34. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19820801)50:3%3C423::AID-CNCR2820500307%3E3.0.CO;2-O link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7046900 PubMed]
 +
## '''Update:''' Rivkin SE, Green SJ, Lew D, Costanzi JJ, Athens JW, Osborne CK, Vaughn CB, Martino S. Adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil, vincristine, and prednisone compared with single-agent L-phenylalanine mustard for patients with operable breast carcinoma and positive axillary lymph nodes: 20-year results of a Southwest Oncology Group study. Cancer. 2003 Jan 1;97(1):21-9. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.10982 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12491501 PubMed]
 +
# Tormey DC, Weinberg VE, Holland JF, Weiss RB, Glidewell OJ, Perloff M, Falkson G, Falkson HC, Henry PH, Leone LA, Rafla S, Ginsberg SJ, Silver RT, Blom J, Carey RW, Schein PS, Lesnick GJ. A randomized trial of five and three drug chemotherapy and chemoimmunotherapy in women with operable node positive breast cancer. J Clin Oncol. 1983 Feb;1(2):138-45. [https://ascopubs.org/doi/abs/10.1200/JCO.1983.1.2.138 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6366133 PubMed]
 +
# '''SWOG S7827:''' Rivkin SE, Green S, Metch B, Jewell WR, Costanzi JJ, Altman SJ, Minton JP, O'Bryan RM, Osborne CK. One versus 2 years of CMFVP adjuvant chemotherapy in axillary node-positive and estrogen receptor-negative patients: a Southwest Oncology Group study. J Clin Oncol. 1993 Sep;11(9):1710-6. [https://ascopubs.org/doi/abs/10.1200/JCO.1993.11.9.1710 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8355037 PubMed]
 +
# '''SWOG S8313:''' Budd GT, Green S, O'Bryan RM, Martino S, Abeloff MD, Rinehart JJ, Hahn R, Harris J, Tormey D, O'Sullivan J, Osborne CK. Short-course FAC-M versus 1 year of CMFVP in node-positive, hormone receptor-negative breast cancer: an intergroup study. J Clin Oncol. 1995 Apr;13(4):831-9. [https://ascopubs.org/doi/abs/10.1200/JCO.1995.13.4.831 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7707108 PubMed]
 +
# '''SWOG S7821:''' Rivkin SE, Green S, O'Sullivan J, Cruz AB, Abeloff MD, Jewell WR, Costanzi JJ, Farrar WB, Osborne CK. Adjuvant CMFVP versus adjuvant CMFVP plus ovariectomy for premenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study. J Clin Oncol. 1996 Jan;14(1):46-51. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.1.46 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8558219 PubMed]
  
−
==FATA-GIM3==
+
==CPB {{#subobject:0d159a|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1===
+
CPB: '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''latinol (Cisplatin), '''<u>B</u>'''CNU (Carmustine)
−
*[[Breast_cancer,_ER-positive#Anastrozole_monotherapy_2|Anastrazole]] x 5 y
+
===Regimen {{#subobject:683965|Variant=1}}===
−
===Arm 2===
 
−
*[[Breast_cancer,_ER-positive#Exemestane_monotherapy|Exemestane]] x 5 y
 
−
===Arm 3===
 
−
*[[Breast_cancer,_ER-positive#Letrozole_monotherapy_2|Letrozole]] x 5 y
 
−
===Arm 4===
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 2 y, then [[Breast_cancer,_ER-positive#Anastrozole_monotherapy_2|Anastrazole]] x 3 y
 
−
===Arm 5===
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 2 y, then [[Breast_cancer,_ER-positive#Exemestane_monotherapy|Exemestane]] x 3 y
 
−
===Arm 6===
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 2 y, then [[Breast_cancer,_ER-positive#Letrozole_monotherapy_2|Letrozole]] x 3 y
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Approach'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|AI x 5 y
+
|[https://ascopubs.org/doi/full/10.1200/JCO.2005.10.202 Peters et al. 2005 (CALGB 9082)]
−
| style="background-color:#ffffbf" |Seems not superior
+
| style="background-color:#1a9851" |Phase III (E-de-esc)
−
|-
+
|HD-CPB with auto HSCT
−
|Tamoxifen x 2 y, then AI x 3 y
 
 
| style="background-color:#ffffbf" |Seems not superior
 
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
 +
''Note: this trial is of important historic significance. Although neither arm was standard of care, the results established the non-value of high-dose therapy with autologous HSCT in the adjuvant treatment of breast cancer.''
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Cisplatin (Platinol)]]
 +
*[[Carmustine (BCNU)]]
 
===References===
 
===References===
−
# De Placido S, Gallo C, De Laurentiis M, Bisagni G, Arpino G, Sarobba MG, Riccardi F, Russo A, Del Mastro L, Cogoni AA, Cognetti F, Gori S, Foglietta J, Frassoldati A, Amoroso D, Laudadio L, Moscetti L, Montemurro F, Verusio C, Bernardo A, Lorusso V, Gravina A, Moretti G, Lauria R, Lai A, Mocerino C, Rizzo S, Nuzzo F, Carlini P, Perrone F; GIM Investigators. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):474-485. Epub 2018 Feb 23. Erratum in: Lancet Oncol. 2018 Apr;19(4):e184. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30116-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29482983 PubMed]
+
# '''CALGB 9082:''' Peters WP, Rosner GL, Vredenburgh JJ, Shpall EJ, Crump M, Richardson PG, Schuster MW, Marks LB, Cirrincione C, Norton L, Henderson IC, Schilsky RL, Hurd DD. Prospective, randomized comparison of high-dose chemotherapy with stem-cell support versus intermediate-dose chemotherapy after surgery and adjuvant chemotherapy in women with high-risk primary breast cancer: a report of CALGB 9082, SWOG 9114, and NCIC MA-13. J Clin Oncol. 2005 Apr 1;23(10):2191-200. Epub 2005 Mar 14. [https://ascopubs.org/doi/full/10.1200/JCO.2005.10.202 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15767638 PubMed]
  
−
==FinXX==
+
==CTCb, then auto HSCT {{#subobject:7a4fec|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Control)===
+
CTCb: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''hiotepa, '''<u>C</u>'''ar'''<u>b</u>'''oplatin
−
*[[Breast_cancer#Docetaxel_monotherapy_2|T (Docetaxel)]] x 3, then [[Breast_cancer#FEC_2|CEF]] x 3
+
<br>STAMP-V
−
===Arm 2 (Experimental)===
+
===Regimen {{#subobject:9d0c8a|Variant=1}}===
−
*TX x 3, then CEX x 3
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|T x 3, then CEF x 3
+
|[http://jco.ascopubs.org/content/8/7/1239.long Eder et al. 1990]
−
|style="background-color:#fee08b"|Might have inferior RFS
+
| style="background-color:#91cf61" |Phase I/II
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|TX x 3, then CEX x 3
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(98)01350-6/fulltext Rodenhuis et al. 1998]
−
|style="background-color:#d9ef8b"|Might have superior RFS
+
| style="background-color:#1a9851" |Randomized Phase II (E-esc)
 +
|Standard adjuvant therapy
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
−
|}
+
|[https://www.sciencedirect.com/science/article/pii/S0140673600028415 Bergh et al. 2000 (SBG 9401)]
−
===References===
+
| style="background-color:#1a9851" |Phase III (C)
−
# Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Asola R, Kokko R, Ahlgren J, Auvinen P, Hemminki A, Paija O, Helle L, Nuortio L, Villman K, Nilsson G, Lahtela SL, Lehtiö K, Pajunen M, Poikonen P, Nyandoto P, Kataja V, Bono P, Leinonen M, Lindman H; FinXX Study Investigators. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial. Lancet Oncol. 2009 Dec;10(12):1145-51. Epub 2009 Nov 10. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70307-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19906561 PubMed]
+
|[[Complex_multipart_regimens#SBG_9401|See link]]
−
## '''Update:''' Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Paija O, Helle L, Villman K, Nyandoto P, Nilsson G, Pajunen M, Asola R, Poikonen P, Leinonen M, Kataja V, Bono P, Lindman H. Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial. J Clin Oncol. 2012 Jan 1;30(1):11-8. Epub 2011 Nov 21. [https://ascopubs.org/doi/full/10.1200/JCO.2011.35.4639 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22105826 PubMed]
+
| style="background-color:#fc8d59" |[[Complex_multipart_regimens#SBG_9401|See link]]
−
 
 
−
==FNCLCC PACS 01==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1 (Control)===
 
−
*[[Breast_cancer#FEC_2|FEC]] x 6
 
−
===Arm 2 (Experimental)===
 
−
*[[Breast_cancer#FEC_2|FEC]] x 3, then [[Breast_cancer#Docetaxel_monotherapy_2|D]] x 3
 
−
===Comparative efficacy===
 
−
''Note: efficacy is based on the 2012 update.''
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|FEC
+
|[https://www.nejm.org/doi/full/10.1056/NEJMoa022794 Rodenhuis et al. 2003]
−
| style="background-color:#d73027" |Inferior OS (*)
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
|-
+
|[[Breast_cancer#FEC_2|FEC]] x 5
−
|FEC-D
+
| style="background-color:#d9ef8b" |Might have superior RFS
−
| style="background-color:#1a9850" |Superior OS (*)
 
 
|-
 
|-
 
|}
 
|}
−
===References===
+
''No longer used, but of historical interest.''
−
<!-- Presented in oral format at the 27th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-11, 2004. -->
+
====Preceding treatment====
−
# 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]
+
*Rodenhuis et al. 1998: [[Breast_cancer#FEC|Neoadjuvant FEC]] x 3, then [[Surgery#Breast_cancer_surgery|surgery]], then [[Breast_cancer#FEC_2|FEC]] x 1
−
## '''Update:''' Coudert B, Asselain B, Campone M, Spielmann M, Machiels JP, Pénault-Llorca F, Serin D, Lévy C, Romieu G, Canon JL, Orfeuvre H, Piot G, Petit T, Jerusalem G, Audhuy B, Veyret C, Beauduin M, Eymard JC, Martin AL, Roché H; UNICANCER Breast Group. Extended benefit from sequential administration of docetaxel after standard fluorouracil, epirubicin, and cyclophosphamide regimen for node-positive breast cancer: the 8-year follow-up results of the UNICANCER-PACS01 trial. Oncologist. 2012;17(7):900-9. Epub 2012 May 18. [http://theoncologist.alphamedpress.org/content/17/7/900.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399644/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22610153 PubMed]
+
*Rodenhuis et al. 2003: [[Breast_cancer#FEC_2|FEC]] x 4
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup>/day on days -7 to -4
 +
*[[Thiotepa (Thioplex)]] 125 mg/m<sup>2</sup>/day on days -7 to -4
 +
*[[Carboplatin (Paraplatin)]] 200 mg/m<sup>2</sup>/day on days -7 to -4
  
−
==GEICAM 9906==
+
'''Stem cells re-infused on day 0'''
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1 (Control)===
 
−
*[[Breast_cancer#FEC_2|FEC]] x 6
 
−
===Arm 2 (Experimental)===
 
−
*[[Breast_cancer#FEC_2|FEC]] x 4, then [[Breast_cancer#Paclitaxel_monotherapy.2C_weekly_2|weekly T (Taxol)]] x 12
 
  
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|FEC x 6
 
−
|style="background-color:#d73027"|Inferior DFS
 
−
|-
 
−
|FEC x 4, then T
 
−
|style="background-color:#1a9850"|Superior DFS
 
−
|-
 
−
|}
 
 
===References===
 
===References===
−
# 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] [https://www.ncbi.nlm.nih.gov/pubmed/18505968 PubMed]
+
# Eder JP, Elias A, Shea TC, Schryber SM, Teicher BA, Hunt M, Burke J, Siegel R, Schnipper LE, Frei E 3rd, Antman K. A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients. J Clin Oncol. 1990 Jul;8(7):1239-45. [http://jco.ascopubs.org/content/8/7/1239.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2162912 PubMed]
 +
# Rodenhuis S, Richel DJ, van der Wall E, Schornagel JH, Baars JW, Koning CC, Peterse JL, Borger JH, Nooijen WJ, Bakx R, Dalesio O, Rutgers E. Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet. 1998 Aug 15;352(9127):515-21. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(98)01350-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9716055 PubMed]
 +
# '''SBG 9401:''' Bergh J, Wiklund T, Erikstein B, Lidbrink E, Lindman H, Malmström P, Kellokumpu-Lehtinen P, Bengtsson NO, Söderlund G, Anker G, Wist E, Ottosson S, Salminen E, Ljungman P, Holte H, Nilsson J, Blomqvist C, Wilking N; Scandinavian Breast Group 9401 study. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Lancet. 2000 Oct 21;356(9239):1384-91. Erratum in: Lancet 2000 Dec 23-30;356(9248):2196. [https://www.sciencedirect.com/science/article/pii/S0140673600028415 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/11052580 PubMed]
 +
# Rodenhuis S, Bontenbal M, Beex LV, Wagstaff J, Richel DJ, Nooij MA, Voest EE, Hupperets P, van Tinteren H, Peterse HL, TenVergert EM, de Vries EG; Netherlands Working Party on Autologous Transplantation in Solid Tumors. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med. 2003 Jul 3;349(1):7-16. [https://www.nejm.org/doi/full/10.1056/NEJMoa022794 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12840087 PubMed]
  
−
==GEICAM/2003-02==
+
==Cyclophosphamide monotherapy {{#subobject:7b2fec|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, FAC (Control)===
+
===Regimen {{#subobject:9d3c8a|Variant=1}}===
−
*[[Surgery]], then [[Breast_cancer#FAC_2|FAC]] x 6
 
−
===Arm 2, FAC-wP (Experimental)===
 
−
*[[Surgery]], then [[Breast_cancer#FAC_2|FAC]] x 4, then [[Breast_cancer#Paclitaxel_monotherapy.2C_weekly_2|wP]] x 8
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|FAC
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2025018/ Rubens et al. 1975]
−
| style="background-color:#fc8d59" |Seems to have inferior DFS
+
| style="background-color:#1a9851" |Phase III (C)
−
|-
+
|CMFV
−
|FAC-wP
+
| style="background-color:#ffffbf" |Seems not superior
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 
===References===
 
===References===
−
# 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]
+
# Rubens RD, Knight RK, Hayward JL. Chemotherapy of advanced breast cancer: a controlled randomized trial of cyclophosphamide versus a four-drug combination. Br J Cancer. 1975 Dec;32(6):730-6. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2025018/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/766800 PubMed]
 +
# '''DBCG 77B:''' Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. [https://link.springer.com/article/10.1007/BF01806239 link to original article] '''contains verified protocol''' [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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.24969/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20186830 PubMed]
  
−
==GEICAM/2003-10==
+
==ECT, then auto HSCT {{#subobject:7a4gab|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, EC-T (Control)===
+
ECT: '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''hiotepa
−
*[[Surgery]], then [[Breast_cancer#EC_2|EC]] x 4, then [[Breast_cancer#Docetaxel_monotherapy_2|T (Taxotere)]] x 4
+
===Regimen {{#subobject:9d0a2n|Variant=1}}===
−
===Arm 2, ET-X (Experimental)===
 
−
*[[Surgery]], then ET x 4, then [[Breast_cancer#Capecitabine_monotherapy|X]] x 4
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|EC-T
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)67784-7/fulltext Nitz et al. 2005 (WSG AM-01)]
−
| style="background-color:#91cf60" |Seems to have superior IDFS
+
|style="background-color:#1a9851" |Phase III (E-esc)
−
|-
+
|[[Breast_cancer#ddEC|ddEC]] x 4, then ddCMF x 3
−
|ET-X
+
| style="background-color:#91cf60" |Seems to have superior OS
−
| style="background-color:#fc8d59" |Seems to have inferior IDFS
 
 
|-
 
|-
 
|}
 
|}
−
===References===
+
''No longer used, but of historical interest.''
−
# Martín M, Ruiz Simón A, Ruiz Borrego M, Ribelles N, Rodríguez-Lescure Á, Muñoz-Mateu M, González S, Margelí Vila M, Barnadas A, Ramos M, Del Barco Berron S, Jara C, Calvo L, Martínez-Jáñez N, Mendiola Fernández C, Rodríguez CA, Martínez de Dueñas E, Andrés R, Plazaola A, de la Haba-Rodríguez J, López-Vega JM, Adrover E, Ballesteros AI, Santaballa A, Sánchez-Rovira P, Baena-Cañada JM, Casas M, del Carmen Cámara M, Carrasco EM, Lluch A. Epirubicin plus cyclophosphamide followed by docetaxel versus epirubicin plus docetaxel followed by capecitabine as adjuvant therapy for node-positive early breast cancer: results from the GEICAM/2003-10 study. J Clin Oncol. 2015 Nov 10;33(32):3788-95. Epub 2015 Sep 28. [https://ascopubs.org/doi/full/10.1200/JCO.2015.61.9510 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26416999 PubMed]
+
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Epirubicin (Ellence)]]
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Thiotepa (Thioplex)]]
  
−
==GeparDuo==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1, ddAT (Experimental)===
 
−
*ddAT x 4, then [[surgery]]
 
−
===Arm 2, AC-T (Experimental)===
 
−
*[[Breast_cancer#AC|AC]] x 4, then [[Breast_cancer#Docetaxel_monotherapy|T (Taxotere)]] x 4, then [[surgery]]
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|ddAT
 
−
| style="background-color:#d73027" |Inferior pCR rate
 
−
|-
 
−
|AC-T
 
−
| style="background-color:#1a9850" |Superior pCR rate
 
−
|-
 
−
|}
 
 
===References===
 
===References===
−
# von Minckwitz G, Raab G, Caputo A, Schütte M, Hilfrich J, Blohmer JU, Gerber B, Costa SD, Merkle E, Eidtmann H, Lampe D, Jackisch C, du Bois A, Kaufmann M. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol. 2005 Apr 20;23(12):2676-85. [https://ascopubs.org/doi/full/10.1200/JCO.2005.05.078 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15837982 PubMed]
+
# '''WSG AM-01:''' Nitz UA, Mohrmann S, Fischer J, Lindemann W, Berdel WE, Jackisch C, Werner C, Ziske C, Kirchner H, Metzner B, Souchon R, Ruffert U, Schütt G, Pollmanns A, Schmoll HJ, Middecke C, Baltzer J, Schrader I, Wiebringhaus H, Ko Y, Rösel S, Schwenzer T, Wernet P, Hinke A, Bender HG, Frick M; West German Study Group. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial. Lancet. 2005 Dec 3;366(9501):1935-44. Erratum in: Lancet. 2006 Mar 4;367(9512):730. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)67784-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16325695 PubMed]
  
−
==GeparQuinto==
+
==FAC & BCG {{#subobject:19f556|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1A - Control (HER2-negative)===
+
FAC & BCG: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, BCG
−
*[[Breast_cancer#EC|EC]] x 4, then [[Breast_cancer#Docetaxel_monotherapy|Docetaxel]] x 4, then [[surgery]]
+
===Regimen {{#subobject:08e709|Variant=1}}===
−
===Arm 1B - Control (HER2-positive)===
+
{| class="wikitable" style="width: 50%; text-align:center;"  
−
*[[Breast_cancer,_HER2-positive#ECH|ECH]] x 4, then [[Breast_cancer,_HER2-positive#TH_.28Taxotere.29|TH (Taxotere)]] x 4, then [[surgery]]
+
!style="width: 25%"|Study
−
===Arm 2A - Experimental (HER2-negative)===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
*[[Breast_cancer,_triple_negative#EC_.26_Bevacizumab|EC & Bevacizumab]] x 4, then [[Breast_cancer,_triple_negative#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]] x 4, then [[surgery]]
 
−
===Arm 2B - Experimental (HER2-positive)===
 
−
*ECL x 4, then TL (Taxotere) x 4, then [[surgery]]
 
−
===Comparative efficacy===
 
−
====Comparison 1 (HER2-negative)====
 
−
''Note that while this study met the primary efficacy endpoint, the advantage for bevacizumab was only seen in the triple-negative breast cancer patients, with p=0.003 in this subgroup.''
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|No bevacizumab
+
|[https://jamanetwork.com/journals/jama/article-abstract/366766 Buzdar et al. 1979]
−
|style="background-color:#fc8d59"|Seems to have inferior pCR rate
+
| style="background-color:#91cf61" |Non-randomized
−
|-
 
−
|With bevacizumab
 
−
|style="background-color:#91cf60"|Seems to have superior pCR rate
 
−
|-
 
−
|}
 
−
====Comparison 2 (HER2-positive)====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|With lapatinib
 
−
|style="background-color:#fc8d59"|Seems to have inferior pCR rate
 
−
|-
 
−
|With trastuzumab
 
−
|style="background-color:#91cf60"|Seems to have superior pCR rate
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Fluorouracil (5-FU)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
====Immunotherapy====
 +
*[[Bacillus Calmette-Guérin (BCG)]]
 
===References===
 
===References===
−
# von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. [https://www.nejm.org/doi/full/10.1056/NEJMoa1111065 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22276820 PubMed]
+
# Buzdar AU, Blumenschein GR, Gutterman JU, Tashima CK, Hortobagyi GN, Smith TL, Campos LT, Wheeler WL, Hersh EM, Freireich EJ, Gehan EA. Postoperative adjuvant chemotherapy with fluorouracil, doxorubicin, cyclophosphamide, and BCG vaccine: a follow-up report. JAMA. 1979 Oct 5;242(14):1509-13. [https://jamanetwork.com/journals/jama/article-abstract/366766 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/470088 PubMed]
−
# Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, Hilfrich J, Strumberg D, Fasching PA, Kreienberg R, Tesch H, Hanusch C, Gerber B, Rezai M, Jackisch C, Huober J, Kühn T, Nekljudova V, von Minckwitz G; German Breast Group (GBG); Arbeitsgemeinschaft Gynäkologische Onkologie-Breast (AGO-B) Study Group. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012 Feb;13(2):135-44. Epub 2012 Jan 17. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70397-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22257523 PubMed]
 
−
## '''Update:''' Untch M, von Minckwitz G, Gerber B, Schem C, Rezai M, Fasching PA, Tesch H, Eggemann H, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Loibl S; GBG and the AGO-B Study Group. Survival analysis after neoadjuvant chemotherapy with trastuzumab or lapatinib in patients with human epidermal growth factor receptor 2-positive breast cancer in the GeparQuinto (G5) study (GBG 44). J Clin Oncol. 2018 May 1;36(13):1308-1316. Epub 2018 Mar 15. [https://ascopubs.org/doi/full/10.1200/JCO.2017.75.9175 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29543566 PubMed]
 
  
−
==GIM2==
+
==FNC {{#subobject:152c11|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, "q3EC-P" (Control)===
+
FNC: '''<u>F</u>'''luorouracil, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>C</u>'''yclophosphamide
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#EC_2|EC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|P]] x 4
+
<br>CNF: '''<u>C</u>'''yclophosphamide, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>F</u>'''luorouracil
−
===Arm 2, "q3FEC-P" (Experimental)===
+
===Regimen {{#subobject:950f9d|Variant=1}}===
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#FEC_2|FEC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|P]] x 4
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
===Arm 3, "q2EC-P" (Experimental)===
+
!style="width: 25%"|Study
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#ddEC|ddEC]] x 4, then [[Breast_cancer#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|ddP]] x 4
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
===Arm 4, "q2FEC-P" (Experimental)===
+
!style="width: 25%"|Comparator
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#ddFEC|ddEC]] x 4, then [[Breast_cancer#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|ddP]] x 4
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
===Comparative efficacy===
 
−
*Analyzed using a 2 x 2 factorial design
 
−
====Comparison 1====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
|'''Dose density'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Dose-dense (q2wk)
+
|[https://insights.ovid.com/pubmed?pmid=11474254 Ron et al. 2001]
−
|style="background-color:#1a9850"|Superior OS
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 +
|[[Breast_cancer#CMF|CMF]]
 +
| style="background-color:#91cf60" |Seems to have superior DFS
 
|-
 
|-
−
|Standard (q3wk)
+
|[https://insights.ovid.com/pubmed?pmid=14758135 Fountzilas et al. 2004 (HE 10/92)]
−
|style="background-color:#d73027"|Inferior OS
+
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]]
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
−
|}
+
|[https://ascopubs.org/doi/full/10.1200/JCO.2006.07.8576 Toledano et al. 2007 (ARCOSEIN)]
−
====Comparison 2====
+
| style="background-color:#1a9851" |Phase III (C)
−
{| class="wikitable" style="width: 100%; text-align:center;"
+
|FNC & RT
−
|'''Inclusion of 5-FU'''
+
| style="background-color:#ffffbf" |Seems not superior
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Yes (FEC-based)
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|No (EC-based)
 
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
−
===References===
+
====Preceding treatment====
−
# 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. [https://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]
+
*[[Surgery#Lumpectomy|Breast-conserving surgery]]
 +
====Chemotherapy====
 +
*[[Fluorouracil (5-FU)]]
 +
*[[Mitoxantrone (Novantrone)]]
 +
*[[Cyclophosphamide (Cytoxan)]]
  
−
==GROCTA-1==
+
'''21-day cycle for 6 cycles'''
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
====Subsequent treatment====
−
|-
+
*ARCOSEIN: RT
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1, CT (Experimental)===
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#CMF|CMF]] x 6, then [[Breast_cancer#Epirubicin_monotherapy|E]] x 4
 
−
===Arm 2, T (Experimental)===
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5 y
 
−
===Arm 3, CTT (Experimental)===
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#CMF|CMF]] x 6, then [[Breast_cancer#Epirubicin_monotherapy|E]] x 4, then [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5 y
 
−
===Comparative efficacy===
 
−
''Note: reported efficacy is based on the 2011 update.''
 
−
====Comparison 1====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
|'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|T
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|CT
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
====Comparison 2====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
|'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|CTT
 
−
|style="background-color:#1a9850"|Superior OS
 
−
|-
 
−
|CT
 
−
|style="background-color:#d73027"|Inferior OS
 
−
|-
 
−
|}
 
−
===References===
 
−
# Boccardo F, Rubagotti A, Bruzzi P, Cappellini M, Isola G, Nenci I, Piffanelli A, Scanni A, Sismondi P, Santi L, Genta F, Saccani F, Sassi M, Malacarne P, Donati D, Farris A, Castagnetta L, Di Carlo A, Traina A, Galletto L, Smerieri F, Buzzi F; Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group. Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. J Clin Oncol. 1990 Aug;8(8):1310-20. [https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.8.1310 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2199618 PubMed]
 
−
## '''Update:''' Boccardo F, Guglielmini P, Parodi A, Rubagotti A. Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen receptor-positive breast cancer patients: very late results of the 'gruppo di ricerca per la chemio-ormonoterapia adiuvante (GROCTA)' 01-Trial in early breast cancer. Breast Cancer Res Treat. 2011 Apr;126(3):653-61. Epub 2011 Feb 24. [https://link.springer.com/article/10.1007%2Fs10549-011-1405-6 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21347647 PubMed]
 
  
−
==HannaH==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1, IV trastuzumab===
 
−
*[[Breast_cancer,_HER2-positive#TH_.28Taxotere.29|TH]] x 4, then [[Breast_cancer,_HER2-positive#FEC_.26_H|FEC & H]] x 4, then [[Surgery#Breast_cancer_surgery|surgery]], then adjuvant [[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy_2|trastuzumab]]
 
−
===Arm 2, SC trastuzumab===
 
−
*[[Breast_cancer,_HER2-positive#TH_.28Taxotere.2FSC.29|TH]] x 4, then [[Breast_cancer,_HER2-positive#FEC_.26_H_.28SC.29|FEC & H]] x 4, then [[Surgery#Breast_cancer_surgery|surgery]], then adjuvant [[Breast_cancer,_HER2-positive#Trastuzumab_and_hyaluronidase_monotherapy|trastuzumab and hyaluronidase]]
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Route of administration'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|IV trastuzumab
 
−
|style="background-color:#eeee01"|Non-inferior pCR rate
 
−
|-
 
−
|SC trastuzumab
 
−
|style="background-color:#eeee01"|Non-inferior pCR rate
 
−
|-
 
−
|}
 
 
===References===
 
===References===
−
# Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. Epub 2012 Aug 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70329-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22884505 PubMed]
+
# Ron IG, Wigler N, Borovik R, Brufman G, Rizel S, Shani A, Brenner J, Farbstein H, Dale A, Inbar MJ, Brenner HJ, Chaitchik S, Catane R. CMF (cyclophosphamide, methotrexate, 5-fluorouracil) versus CNF (cyclophosphamide, mitoxantrone, 5-fluorouracil) as adjuvant chemotherapy for stage II lymph-node positive breast cancer: a phase III randomized multicenter study. Am J Clin Oncol. 2001 Aug;24(4):323-7. [https://insights.ovid.com/pubmed?pmid=11474254 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11474254 PubMed]
−
## '''Update:''' Jackisch C, Stroyakovskiy D, Pivot X, Ahn JS, Melichar B, Chen SC, Meyenberg C, Al-Sakaff N, Heinzmann D, Hegg R. Subcutaneous vs intravenous trastuzumab for patients with ERBB2-positive early breast cancer: final analysis of the HannaH phase 3 randomized clinical trial. JAMA Oncol. 2019 May 1;5(5):e190339. Epub 2019 May 9. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2730632 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512301/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30998824 PubMed]
+
# '''HE 10/92:''' Fountzilas G, Stathopoulos G, Kouvatseas G, Polychronis A, Klouvas G, Samantas E, Zamboglou N, Kyriakou K, Adamou A, Pectasidis D, Ekonomopoulos T, Kalofonos HP, Bafaloukos D, Georgoulias V, Razis E, Koukouras D, Zombolas V, Kosmidis P, Skarlos D, Pavlidis N; Hellenic Cooperative Oncology Group. Adjuvant cytotoxic and endocrine therapy in pre- and postmenopausal patients with breast cancer and one to nine infiltrated nodes: five-year results of the Hellenic Cooperative Oncology Group randomized HE 10/92 study. Am J Clin Oncol. 2004 Feb;27(1):57-67. [https://insights.ovid.com/pubmed?pmid=14758135 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14758135 PubMed]
 +
# '''ARCOSEIN:''' Toledano A, Azria D, Garaud P, Fourquet A, Serin D, Bosset JF, Miny-Buffet J, Favre A, Le Floch O, Calais G. Phase III trial of concurrent or sequential adjuvant chemoradiotherapy after conservative surgery for early-stage breast cancer: final results of the ARCOSEIN trial. J Clin Oncol. 2007 Feb 1;25(4):405-10. Erratum in: J Clin Oncol. 2007 Jun 1;25(16):2334. [https://ascopubs.org/doi/full/10.1200/JCO.2006.07.8576 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17264336 PubMed]
  
−
==HORG Polyzos et al. 2010==
+
==Levamisole monotherapy {{#subobject:b051c5|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Experimental)===
+
===Regimen {{#subobject:ec3553|Variant=1}}===
−
*[[Surgery]], then [[Breast_cancer#ddT_.28Taxotere.29|D]] x 4, then [[Breast_cancer#EC_2|EC]] x 4
 
−
===Arm 2 (Control)===
 
−
*[[Surgery]], then [[Breast_cancer#FEC_2|FEC]] x 6
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|D/EC
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(76)91337-4/fulltext Rojas et al. 1976]
−
| style="background-color:#91cf60" |Seems to have superior DFS
+
|style="background-color:#1a9851"|Randomized (E-esc)
 +
|[[#Observation|Observation]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 
|-
 
|-
−
|FEC
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(80)90173-7/fulltext Brincker et al. 1980]
−
| style="background-color:#fc8d59" |Seems to have inferior DFS
+
|style="background-color:#1a9851"|Randomized (E-switch-ooc)
 +
|RT
 +
| style="background-color:#fc8d59" |Seems to have inferior RFS
 
|-
 
|-
 
|}
 
|}
 +
''Note: Rojas et al. 1976 included patients with inoperable breast cancer; definitive therapy was RT.''
 +
====Preceding treatment====
 +
*Rojas et al. 1976: Radiotherapy
 +
*Brincker et al. 1980: [[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Immunotherapy====
 +
*[[Levamisole (Ergamisol)]]
 
===References===
 
===References===
−
# Polyzos A, Malamos N, Boukovinas I, Adamou A, Ziras N, Kalbakis K, Kakolyris S, Syrigos K, Papakotoulas P, Kouroussis C, Karvounis N, Vamvakas L, Christophyllakis C, Athanasiadis A, Varthalitis I, Georgoulias V, Mavroudis D. FEC versus sequential docetaxel followed by epirubicin/cyclophosphamide as adjuvant chemotherapy in women with axillary node-positive early breast cancer: a randomized study of the Hellenic Oncology Research Group (HORG). Breast Cancer Res Treat. 2010 Jan;119(1):95-104. Epub 2009 Jul 28. [https://link.springer.com/article/10.1007%2Fs10549-009-0468-0 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19636702 PubMed]
+
# Rojas AF, Feierstein JN, Mickiewicz E, Glait H, Olivari AJ. Levamisole in advanced human breast cancer. Lancet. 1976 Jan 31;1(7953):211-5. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(76)91337-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/55529 PubMed]
 +
# Brincker H, Mouridsen HT, Andersen KW, Andersen J, Castberg T, Fischermann K, Henriksen E, Hou-Jensen C, Johansen H, Rossing N, Rorth M; Executive Committee of the Danish Breast Cancer Cooperative Group. Increased breast-cancer recurrence rate after adjuvant therapy with levamisole: a preliminary report. Lancet. 1980 Oct 18;2(8199):824-7. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(80)90173-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6107500 PubMed]
  
−
==HORG CT/07.17==
+
==Melphalan monotherapy {{#subobject:b062c5|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1===
+
P: '''<u>P</u>'''henylalanine mustard (Melphalan)
−
*[[Surgery]], then [[Breast_cancer#ddFEC|ddFEC]] x 4, then [[Breast_cancer#ddT_.28Taxotere.29|D]] x 4
+
===Regimen {{#subobject:ec3663|Variant=1}}===
−
===Arm 2===
 
−
*[[Surgery]], then [[Breast_cancer#TC_.28Taxotere.29|TC]] x 6
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|ddFEC → D
+
|[https://www.nejm.org/doi/full/10.1056/NEJM197501162920301 Fisher et al. 1975 (NSABP B-05)]
−
|style="background-color:#ffffbf"|Inconclusive whether non-inferior
+
|style="background-color:#1a9851"|Phase III (E-esc)
 +
|[[#Placebo|Placebo]]
 +
| style="background-color:#d9ef8b" |Might have superior DFS (*)
 
|-
 
|-
−
|TC
+
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 Fisher et al. 1977 (NSABP B-07)]
−
|style="background-color:#ffffbf"|Inconclusive whether non-inferior
+
| style="background-color:#1a9851" |Phase III (C)
 +
|[[#PF|PF]]
 +
| style="background-color:#fc8d59" |Seems to have inferior RFS
 
|-
 
|-
−
|}
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(83)91385-5/fulltext Rubens et al. 1983]
−
===References===
+
|style="background-color:#1a9851"|Phase III (E-esc)
−
# 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] [https://www.ncbi.nlm.nih.gov/pubmed/27502729 PubMed]
+
|[[#Observation|Observation]]
−
 
+
| style="background-color:#d9ef8b" |Might have superior RFS
−
==IES==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
IES: '''<u>I</u>'''ntergroup '''<u>E</u>'''xemestane '''<u>S</u>'''tudy
 
−
===Arm 1, monotherapy (Control)===
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5y
 
−
===Arm 2, sequential (Experimental)===
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 2-3y, then [[Breast_cancer,_ER-positive#Exemestane_monotherapy_2|Exemestane]] x 2-3y
 
−
===Comparative efficacy===
 
−
''Note: reported efficacy is based on the 2011 update.''
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Tamoxifen x 5y
 
−
|style="background-color:#fc8d59"|Seems to have inferior OS
 
−
|-
 
−
|Tamoxifen x 2-3y, then Exemestane x 2-3y (5y total)
 
−
|style="background-color:#91cf60"|Seems to have superior OS
 
 
|-
 
|-
 
|}
 
|}
 +
''Note: Fisher et al. 1977 is an update for NSABP B-05 and also the primary results for NSABP B-07. Efficacy for NSABP B-05 is based on the 1986 update.''
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Melphalan (Alkeran)]]
 
===References===
 
===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. [https://www.nejm.org/doi/full/10.1056/NEJMoa040331 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15014181 PubMed]
+
# '''NSABP B-05:''' Fisher B, Carbone P, Economou SG, Frelick R, Glass A, Lerner H, Redmond C, Zelen M, Band P, Katrych DL, Wolmark N, Fisher ER. 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer: a report of early findings. N Engl J Med. 1975 Jan 16;292(3):117-22. [https://www.nejm.org/doi/full/10.1056/NEJM197501162920301 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1105174 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. [https://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]
+
## '''Update:''' Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197706)39:6%3C2883::AID-CNCR2820390676%3E3.0.CO;2-9/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/194679 PubMed]
−
## '''Update:''' Bliss JM, Kilburn LS, Coleman RE, Forbes JF, Coates AS, Jones SE, Jassem J, Delozier T, Andersen J, Paridaens R, van de Velde CJ, Lønning PE, Morden J, Reise J, Cisar L, Menschik T, Coombes RC. Disease-related outcomes with long-term follow-up: an updated analysis of the Intergroup Exemestane Study. J Clin Oncol. 2012 Mar 1;30(7):709-17. Epub 2011 Oct 31. [https://ascopubs.org/doi/full/10.1200/JCO.2010.33.7899 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22042946 PubMed]
+
## '''Update:''' Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986 Jun;4(6):929-41. [https://ascopubs.org/doi/full/10.1200/JCO.1986.4.6.929 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3519883 PubMed]
 +
# '''NSABP B-07:''' Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/194679 PubMed]
 +
# Rubens RD, Hayward JL, Knight RK, Bulbrook RD, Fentiman IS, Chaudary M, Howell A, Bush H, Crowther D, Sellwood RA, George WD, Howat JM. Controlled trial of adjuvant chemotherapy with melphalan for breast cancer. Lancet. 1983 Apr 16;1(8329):839-43. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(83)91385-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6132179 PubMed]
  
−
==IRST-IBIS-03==
+
==MF {{#subobject:e1def3|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1===
+
MF: '''<u>M</u>'''ethotrexate & 5-'''<u>F</u>'''luorouracil
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#Epirubicin_monotherapy|E]], then [[Breast_cancer#CMF|CMF]]
+
===Regimen {{#subobject:c6e0a3|Variant=1}}===
−
===Arm 2===
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#CMF|CMF]], then [[Breast_cancer#Epirubicin_monotherapy|E]]
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!style="width: 50%"|'''Regimen'''
+
!style="width: 25%"|Study
−
!style="width: 50%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|E -> CMF
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200801 Fisher et al. 1989 (NSABP B-13)]
−
| style="background-color:#ffffbf" |Seems not superior
+
| style="background-color:#1a9851" |Phase III (E-esc)
 +
|[[#Observation|Observation]]
 +
| style="background-color:#1a9850" |Superior DFS (*)
 
|-
 
|-
−
|CMF -> E
+
|[https://academic.oup.com/jnci/article-abstract/85/10/812/1024452 Shapiro et al. 1993]
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer#CMF|CMF]]
 
| style="background-color:#ffffbf" |Seems not superior
 
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
−
|}
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.1982 Fisher et al. 1996 (NSABP B-19)]
−
===References===
+
| style="background-color:#1a9851" |Phase III (C)
−
# Amadori D, Silvestrini R, De Lena M, Boccardo F, Rocca A, Scarpi E, Schittulli F, Brandi M, Maltoni R, Serra P, Ponzone R, Biglia N, Gianni L, Tienghi A, Valerio MR, Bonginelli P, Amaducci L, Faedi M, Baldini E, Paradiso A. Randomized phase III trial of adjuvant epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) versus CMF followed by epirubicin in patients with node-negative or 1-3 node-positive rapidly proliferating breast cancer. Breast Cancer Res Treat. 2011 Feb;125(3):775-84. Epub 2010 Dec 4. [https://link.springer.com/article/10.1007%2Fs10549-010-1257-5 link to original article]  [https://www.ncbi.nlm.nih.gov/pubmed/21132360 PubMed]
+
|[[Breast_cancer#CMF|CMF]]
−
==Kümmel et al. 2006==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1, control===
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#EC_2|EC]] x 4, then [[Breast_cancer#CMF|CMF]] x 3
 
−
===Arm 2, experimental===
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then ddEP x 4, then ddCMF x 3
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 50%"|'''Regimen'''
 
−
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|EC-CMF
 
 
| style="background-color:#fee08b" |Might have inferior OS
 
| style="background-color:#fee08b" |Might have inferior OS
−
|-
 
−
|ddEP-ddCMF
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
 
|-
 
|-
 
|}
 
|}
 +
''Note: Reported efficacy for NSABP B-13 is based on the 1996 update.''
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 
===References===
 
===References===
−
# Kümmel S, Krocker J, Kohls A, Breitbach GP, Morack G, Budner M, Blohmer JU, Elling D. Randomised trial: survival benefit and safety of adjuvant dose-dense chemotherapy for node-positive breast cancer. Br J Cancer. 2006 May 8;94(9):1237-44. [https://www.nature.com/articles/6603085 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361407/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/16622463 PubMed]
+
# '''NSABP B-13:''' Fisher B, Redmond C, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, Glass A, Foster R, Caplan R. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med. 1989 Feb 23;320(8):473-8. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200801 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2644531 PubMed]
 +
## '''Update:''' Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.1982 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8683228 PubMed]
 +
## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://ascopubs.org/doi/full/10.1200/JCO.2006.06.9054 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16921044 PubMed]
 +
# Shapiro CL, Gelman RS, Hayes DF, Osteen R, Obando A, Canellos GP, Frei E 3rd, Henderson IC. Comparison of adjuvant chemotherapy with methotrexate and fluorouracil with and without cyclophosphamide in breast cancer patients with one to three positive axillary lymph nodes. J Natl Cancer Inst. 1993 May 19;85(10):812-7. [https://academic.oup.com/jnci/article-abstract/85/10/812/1024452 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8487326 PubMed]
 +
# '''NSABP B-19:''' Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.1982 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8683228 PubMed]
 +
## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://ascopubs.org/doi/full/10.1200/JCO.2006.06.9054 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16921044 PubMed]
  
−
==Loesch et al. 2010==
+
==MV {{#subobject:eb48eb|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, control===
+
MV: '''<u>M</u>'''ethotrexate & '''<u>V</u>'''inblastine
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T (Taxol)]] x 4
+
===Regimen {{#subobject:883648|Variant=1}}===
−
===Arm 2, experimental===
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AT_.28Taxol.29|AT (Taxol)]] x 4, then [[#Paclitaxel_monotherapy.2C_weekly_2|wP]] x 12
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|AC-P
+
|[https://onlinelibrary.wiley.com/doi/10.1002/cncr.11396/full Assikis et al. 2003]
−
| style="background-color:#ffffbf" |Seems not superior
+
|style="background-color:#1a9851"|Phase III (E-switch-ooc)
−
|-
+
|[[Complex_multipart_regimens#Assikis_et_al._2003|See link]]
−
|AP-WP
+
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#Assikis_et_al._2003|See link]]
−
| style="background-color:#ffffbf" |Seems not superior
 
 
|-
 
|-
 
|}
 
|}
−
===References===
+
''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.''
−
# Loesch D, Greco FA, Senzer NN, Burris HA, Hainsworth JD, Jones S, Vukelja SJ, Sandbach J, Holmes F, Sedlacek S, Pippen J, Lindquist D, McIntyre K, Blum JL, Modiano MR, Boehm KA, Zhan F, Asmar L, Robert N. Phase III multicenter trial of doxorubicin plus cyclophosphamide followed by paclitaxel compared with doxorubicin plus paclitaxel followed by weekly paclitaxel as adjuvant therapy for women with high-risk breast cancer. J Clin Oncol. 2010 Jun 20;28(18):2958-65. Epub 2010 May 17. [https://ascopubs.org/doi/full/10.1200/JCO.2009.24.1000 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20479419 PubMed]
+
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#FAC|FAC]] x 6
 +
====Chemotherapy====
 +
*[[Methotrexate (MTX)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vinblastine (Velban)]] 1.7 mg/m<sup>2</sup>/day continuous infusion over 120 hours, started on day 1 (total dose per cycle: 8.5 mg/m<sup>2</sup>)
  
−
==Mavroudis et al. 2017==
+
====Supportive medications====
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
*[[Folinic acid (Leucovorin)]] rescue
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1, sequential===
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#Epirubicin_monotherapy|Epirubicin]], then [[Breast_cancer#Docetaxel_monotherapy_2|Docetaxel]]
 
−
===Arm 2, concurrent===
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then Docetaxel & Epirubicin
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Schedule'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Sequential
 
−
|style="background-color:#d9ef8b"|Might have superior DFS
 
−
|-
 
−
|Concurrent
 
−
|style="background-color:#fee08b"|Might have inferior DFS
 
−
|-
 
−
|}
 
−
===References===
 
−
# 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/pmc/articles/PMC5584474/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28641315 PubMed]
 
  
−
==Milan trial==
+
'''21- to 28-day cycle for 4 cycles'''
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1 (Experimental)===
 
−
*[[Surgery]], then [[Breast_cancer#Doxorubicin_monotherapy|A]] x 4, then [[Breast_cancer#CMF|CMF]] x 8
 
−
===Arm 2 (Experimental)===
 
−
*[[Surgery]], then A alternating with CMF every 2 cycles (12 cycles total)
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 50%"|Approach
 
−
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Sequential
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|Alternating
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
===References===
 
−
# Buzzoni R, Bonadonna G, Valagussa P, Zambetti M. Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil in the treatment of resectable breast cancer with more than three positive axillary nodes. J Clin Oncol. 1991 Dec;9(12):2134-40. [https://ascopubs.org/doi/abs/10.1200/JCO.1991.9.12.2134 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1960555 PubMed]
 
−
## '''Update:''' Bonadonna G, Zambetti M, Valagussa P. Sequential or alternating doxorubicin and CMF regimens in breast cancer with more than three positive nodes: ten-year results. JAMA. 1995 Feb 15;273(7):542-7. [https://jamanetwork.com/journals/jama/fullarticle/387001 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7837388 PubMed]
 
  
−
==NCCTG N9831==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
''The taxane used in this trial was paclitaxel.''
 
−
===Arm 1, no trastuzumab (Control)===
 
−
*[[Breast_cancer#AC|AC]], then [[Breast_cancer#Paclitaxel_monotherapy.2C_weekly_2|T]]
 
−
===Arm 2, sequential trastuzumab (Experimental)===
 
−
*[[Breast_cancer#AC|AC]], then [[Breast_cancer#Paclitaxel_monotherapy.2C_weekly_2|T]], then [[Breast_cancer#Trastuzumab_monotherapy_2|H]]
 
−
===Arm 3, concurrent trastuzumab (Experimental)===
 
−
*[[Breast_cancer#AC|AC]], then [[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH]]
 
−
===Comparative efficacy===
 
−
====Comparison 1====
 
−
''Note: Arm 2 was not included in this joint analysis. Efficacy is based on the 2014 update.''
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 50%"|Regimen
 
−
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|AC, then T
 
−
|style="background-color:#d73027"|Inferior OS
 
−
|-
 
−
|AC, then TH
 
−
|style="background-color:#1a9850"|Superior OS
 
−
|-
 
−
|}
 
−
====Comparison 2====
 
−
''Note: efficacy is as reported in the 2011 update.''
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 50%"|Trastuzumab-containing regimens
 
−
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|AC, then T, then H
 
−
|style="background-color:#fee08b"|Might have inferior DFS
 
−
|-
 
−
|AC, then TH
 
−
|style="background-color:#d9ef8b"|Might have superior DFS
 
−
|-
 
−
|}
 
 
===References===
 
===References===
−
# 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa052122 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16236738 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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.11396/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12767083 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. [https://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. [https://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]
 
  
−
==NCIC CTG MA.21==
+
==Observation==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, CEF (Control)===
+
===Regimen===
−
*[[Surgery]], then [[Breast_cancer#FEC_2|FEC]] x 6
 
−
===Arm 2, AC/T (Control)===
 
−
*[[Surgery]], then [[Breast_cancer#AC_2|AC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T (Taxol)]] x 4
 
−
===Arm 3, ddEC/T (Experimental)===
 
−
*[[Surgery]], then [[Breast_cancer#ddEC|ddEC]] x 6, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T (Taxol)]] x 4
 
−
===Comparative efficacy===
 
−
====Comparison 1====
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|AC/T
+
|[https://www.nejm.org/doi/full/10.1056/NEJM197602192940801 Bonadonna et al. 1976]
 +
|style="background-color:#1a9851"|Phase III (C)
 +
|[[Breast_cancer#CMF|CMF]]
 
|style="background-color:#d73027"|Inferior RFS
 
|style="background-color:#d73027"|Inferior RFS
 
|-
 
|-
−
|CEF
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(80)90057-4/fulltext Lacour et al. 1980]
−
|style="background-color:#1a9850"|Superior RFS
+
|style="background-color:#1a9851"|Phase III (C)
 +
|Polya.Polyu
 +
| style="background-color:#fee08b" |Might have inferior OS
 
|-
 
|-
−
|}
+
|rowspan=3|[https://link.springer.com/article/10.1007/BF01806239 Brinker et al. 1983 (DBCG 77B)]
−
====Comparison 2====
+
|rowspan=3 style="background-color:#1a9851" |Phase III (C)
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
|1. [[Breast_cancer#CMF|CMF]]
−
!'''Regimen'''
+
| style="background-color:#fc8d59" |Seems to have inferior OS (*)
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
|-
 +
|2. [[#Cyclophosphamide_monotherapy|Cyclophosphamide]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS (*)
 
|-
 
|-
−
|AC/T
+
|3. [[#Levamisole_monotherapy|Levamisole]]
−
|style="background-color:#d73027"|Inferior RFS
+
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
−
|ddEC/T
+
|rowspan = 2|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS III)]
−
|style="background-color:#1a9850"|Superior RFS
+
|rowspan = 2 style="background-color:#1a9851" |Phase III (C)
 +
|1. [[#CMFPT|CMFPT]]
 +
| style="background-color:#d73027" |Inferior DFS
 
|-
 
|-
−
|}
+
|2. [[#PT|PT]]
−
====Comparison 3====
+
| style="background-color:#d73027" |Inferior DFS
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|CEF
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS IV)]
−
| style="background-color:#ffffbf" |Seems not superior
+
|style="background-color:#1a9851" |Phase III (C)
 +
|[[#PT|PT]]
 +
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
|-
 
|-
−
|ddEC/T
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200801 Fisher et al. 1989 (NSABP B-13)]
−
| style="background-color:#ffffbf" |Seems not superior
+
| style="background-color:#1a9851" |Phase III (C)
 +
|Sequential MF
 +
| style="background-color:#d73027" |Inferior DFS (*)
 
|-
 
|-
−
|}
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200803 Mansour et al. 1989 (INT-0011)]
−
===References===
+
| style="background-color:#1a9851" |Phase III (C)
−
# Burnell M, Levine MN, Chapman JA, Bramwell V, Gelmon K, Walley B, Vandenberg T, Chalchal H, Albain KS, Perez EA, Rugo H, Pritchard K, O'Brien P, Shepherd LE. Cyclophosphamide, epirubicin, and fluorouracil versus dose-dense epirubicin and cyclophosphamide followed by paclitaxel versus doxorubicin and cyclophosphamide followed by paclitaxel in node-positive or high-risk node-negative breast cancer. J Clin Oncol. 2010 Jan 1;28(1):77-82. Epub 2009 Nov 9. [https://ascopubs.org/doi/full/10.1200/JCO.2009.22.1077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799234/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19901117 PubMed]
+
|[[#CMFP|CMFP]]
−
 
+
|style="background-color:#d73027"|Inferior DFS
−
==NEAT==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://ascopubs.org/doi/full/10.1200/JCO.2001.19.19.3929 Paradiso et al. 2001]
−
|}
+
| style="background-color:#1a9851" |Phase III (C)
−
===Arm 1 (Control)===
+
|[[Breast_cancer#FEC_2|FEC]]
−
*[[Breast_cancer#CMF|CMF]] x 6
+
| style="background-color:#fc8d59" |Seems to have inferior DFS
−
===Arm 2 (Experimental)===
 
−
*[[Breast_cancer#Epirubicin_monotherapy|Epirubicin]] x 4, then [[Breast_cancer#CMF|CMF]] x 4
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 50%"|Regimen
 
−
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|CMF x 6
+
|[http://jco.ascopubs.org/content/21/6/976.long Henderson et al. 2003 (INT 0148/CALGB 9344)]
 +
|style="background-color:#1a9851"|Phase III (C)
 +
|[[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel q3wk]]
 
|style="background-color:#d73027"|Inferior OS
 
|style="background-color:#d73027"|Inferior OS
 
|-
 
|-
−
|E x 4, then CMF x 4
+
|[http://jco.ascopubs.org/content/23/16/3686.long Mamounas et al. 2005 (NSABP B-28)]
−
|style="background-color:#1a9850"|Superior OS
+
|style="background-color:#1a9851"|Phase III (C)
 +
|[[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel q3wk]]
 +
|style="background-color:#d73027"|Inferior DFS
 
|-
 
|-
 
|}
 
|}
 +
''No further systemic treatment; many of these trials incorporated RT, however (see individual papers for details). Reported efficacy for DBCG 77B is based on the 2010 update. Reported efficacy for NSABP B-13 is based on the 1996 update.''
 +
====Preceding treatment====
 +
*Bonadonna et al. 1976: [[Surgery#Mastectomy|Mastectomy]]
 +
*ECOG E1180: [[Surgery#Modified_radical_mastectomy|Modified radical mastectomy]] or [[Surgery#Mastectomy|total mastectomy]] with [[Surgery#Axillary_lymph_node_dissection|low axillary-node dissection]]
 +
*INT 0148/CALGB 9344: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4 versus high-dose AC x 4 versus very-high-dose AC x 4
 +
*NSABP B-28: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4
 +
 
===References===
 
===References===
−
<!-- no pre-pub disclosed -->
+
# Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, De Lena M, Tancini G, Bajetta E, Musumeci R, Veronesi U. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976 Feb 19;294(8):405-10. [https://www.nejm.org/doi/full/10.1056/NEJM197602192940801 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1246307 PubMed]
−
# Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. [https://www.nejm.org/doi/full/10.1056/NEJMoa052084 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17079759 PubMed]
+
## '''Update:''' Bonadonna G, Rossi A, Valagussa P, Banfi A, Veronesi U. The CMF program for operable breast cancer with positive axillary nodes: updated analysis on the disease-free interval, site of relapse and drug tolerance. Cancer. 1977 Jun;39(6 Suppl):2904-15. [https://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. [https://www.nejm.org/doi/ref/10.1056/NEJM199504063321401 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7877646 PubMed]
 +
# Lacour J, Lacour F, Spira A, Michelson M, Petit JY, Delage G, Sarrazin D, Contesso G, Viguier J. Adjuvant treatment with polyadenylic-polyuridylic acid (Polya-Polyu) in operable breast cancer. Lancet. 1980 Jul 26;2(8187):161-4. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(80)90057-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6105336 PubMed]
 +
# '''DBCG 77B:''' Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. [https://link.springer.com/article/10.1007/BF01806239 link to original article] '''contains verified protocol''' [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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.24969/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20186830 PubMed]
 +
# '''LBCS III/IV:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. [https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6144974 PubMed]
 +
# '''NSABP B-13:''' Fisher B, Redmond C, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, Glass A, Foster R, Caplan R. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med. 1989 Feb 23;320(8):473-8. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200801 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2644531 PubMed]
 +
## '''Update:''' Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.1982 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8683228 PubMed]
 +
## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://ascopubs.org/doi/full/10.1200/JCO.2006.06.9054 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16921044 PubMed]
 +
# '''INT-0011:''' Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med. 1989 Feb 23;320(8):485-90. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200803 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2915651 PubMed]
 +
# '''LCBS V:''' Goldhirsch A, Gelber RD; Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med. 1989 Feb 23;320(8):491-6. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200804 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2644533 PubMed]
 +
# Paradiso A, Schittulli F, Cellamare G, Mangia A, Marzullo F, Lorusso V, De Lena M. Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer. J Clin Oncol. 2001 Oct 1;19(19):3929-37. [https://ascopubs.org/doi/full/10.1200/JCO.2001.19.19.3929 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11579113 PubMed]
 +
# '''INT 0148/CALGB 9344:''' Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. [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]
 +
<!-- Presented in abstract form at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003; interim results were presented at the 2000 NIH Consensus Development Conference, Bethesda, MD, November 1-3, 2000. -->
 +
# '''NSABP B-28:''' Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. [http://jco.ascopubs.org/content/23/16/3686.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15897552 PubMed]
  
−
==NeoALTTO==
+
==Oophorectomy==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, trastuzumab (C)===
+
===Regimen===
−
*[[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy|Trastuzumab]] x 6 wk, then [[Breast_cancer,_HER2-positive#TH_.28Taxol.29|TH (Taxol)]] x 12 wk, then [[surgery]], then [[Breast_cancer#FEC_2|FEC]] x 3, then [[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy_2|Trastuzumab]] x 34 wk
 
−
===Arm 1, lapatinib (E)===
 
−
*Lapatinib x 6 wk, then [[Breast_cancer,_HER2-positive#TL_.28Taxol.29|TL (Taxol)]] x 12 wk, then [[surgery]], then [[Breast_cancer#FEC_2|FEC]] x 3, then Lapatinib x 34 wk
 
−
===Arm 3, lapatinib & trastuzumab (E)===
 
−
*[[Breast_cancer,_HER2-positive#Lapatinib_.26_Trastuzumab|Lapatinib & Trastuzumab]] x 6 wk, then [[Breast_cancer,_HER2-positive#THL_.28Taxol.29|THL (Taxol)]] x 12 wk, then [[surgery]], then [[Breast_cancer#FEC_2|FEC]] x 3, then [[Breast_cancer,_HER2-positive#Lapatinib_.26_Trastuzumab_2|Lapatinib & Trastuzumab]] x 34 wk
 
−
===Comparative efficacy===
 
−
''The primary endpoint was pathologic complete response (pCR) rate. Comparison was only between experimental and control arms (i.e., 2 comparisons).''
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Backbone'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Trastuzumab vs. Lapatinib
+
|[https://www.nejm.org/doi/full/10.1056/NEJM197708182970704 Ahmann et al. 1977]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#1a9851" |Phase III (C)
−
|-
+
|[[#CFP_.26_Oophorectomy|CFP & Oophorectomy]]
−
|Trastuzumab vs. Lapatinib & Trastuzumab
+
| style="background-color:#fc8d59" |Seems to have inferior PFS
−
|style="background-color:#d73027"|Inferior pCR rate
 
−
|-
 
−
|Lapatinib vs. Trastuzumab
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|Lapatinib & Trastuzumab vs. Trastuzumab
 
−
|style="background-color:#1a9850"|Superior pCR rate
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Hormonotherapy====
 +
*[[Endocrine_ablation_surgery#Bilateral_oophorectomy|Bilateral oophorectomy]]
 
===References===
 
===References===
−
# Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61847-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705192/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22257673 PubMed]
+
# Ahmann DL, O'Connell MJ, Hahn RG, Bisel HF, Lee RA, Edmonson JH. An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advanced breast cancer undergoing oophorectomy. N Engl J Med. 1977 Aug 18;297(7):356-60. [https://www.nejm.org/doi/full/10.1056/NEJM197708182970704 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/876327 PubMed]
−
## '''Update:''' de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70320-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25130998 PubMed]
 
  
−
==Neo-tAnGo==
+
==Paclitaxel monotherapy, q3wk {{#subobject:1cb87f|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, EC-ddT===
+
T: '''<u>T</u>'''axol (Paclitaxel)
−
*[[Breast_cancer#EC|EC]] x 4, then [[Breast_cancer#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29|ddT]] x 4, then [[surgery]]
+
<br>P: '''<u>P</u>'''aclitaxel
−
===Arm 2, ddT-EC===
+
<br>pT: '''<u>p</u>'''acli'''<u>T</u>'''axel
−
*[[Breast_cancer#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29|ddT]] x 4, then [[Breast_cancer#EC|EC]] x 4, then [[surgery]]
+
===Variant #1, 175 mg/m<sup>2</sup> q3wk {{#subobject:c084f5|Variant=1}}===
−
===Arm 3, EC-ddTG===
 
−
*[[Breast_cancer#EC|EC]] x 4, then ddTG x 4, then [[surgery]]
 
−
===Arm 4, ddTG-EC===
 
−
*ddTG x 4, then [[Breast_cancer#EC|EC]] x 4, then [[surgery]]
 
−
===Comparative efficacy===
 
−
*Analyzed using a 2 x 2 factorial design
 
−
====Comparison 1====
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
|'''Sequencing'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Taxane first
+
|[http://jco.ascopubs.org/content/21/6/976.long Henderson et al. 2003 (INT 0148/CALGB 9344)]
−
|style="background-color:#91cf60"|Seems to have superior pCR rate
+
| style="background-color:#1a9851" |Phase III (E-RT-esc)
 +
|[[#Observation|Observation]]
 +
| style="background-color:#1a9850" |Superior OS
 
|-
 
|-
−
|EC first
+
|[https://www.nejm.org/doi/full/10.1056/NEJMoa052122 Romond et al. 2005 (NSABP B-31)]
−
|style="background-color:#fc8d59"|Seems to have inferior pCR rate
+
| style="background-color:#1a9851" |Phase III (C)
 +
|[[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)]
−
====Comparison 2====
+
| rowspan="3" style="background-color:#1a9851" |Phase III (C)
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
|1. [[Breast_cancer#Paclitaxel_monotherapy.2C_weekly_2|Weekly Paclitaxel]]
−
|'''Addition of gemcitabine'''
+
| style="background-color:#d73027" |Inferior OS
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Without gemcitabine
+
|2. [[Breast_cancer#Docetaxel_monotherapy_2|Docetaxel q3wk]]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
|-
 
|-
−
|With gemcitabine
+
|3. [[Breast_cancer#Docetaxel_monotherapy_2|Docetaxel weekly]]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#ffffbf" |Seems not superior
−
|-
 
−
|}
 
−
===References===
 
−
# Earl HM, Vallier AL, Hiller L, Fenwick N, Young J, Iddawela M, Abraham J, Hughes-Davies L, Gounaris I, McAdam K, Houston S, Hickish T, Skene A, Chan S, Dean S, Ritchie D, Laing R, Harries M, Gallagher C, Wishart G, Dunn J, Provenzano E, Caldas C; Neo-tAnGo Investigators. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):201-12. Epub 2013 Dec 19. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70554-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24360787 PubMed]
 
−
 
 
−
==NOAH==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1, no trastuzumab (Control)===
 
−
*AT (Taxol) x 3, then T (Taxol) x 3, then CMF x 3, then [[surgery]]
 
−
===Arm 2, with trastuzumab (Experimental)===
 
−
*ATH (Taxol) x 3, then [[Breast_cancer,_HER2-positive#TH_.28Taxol.29|TH]] x 3, then CMF & H x 3, then [[surgery]], then [[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy_2|trastuzumab for a total of 1 year]]
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
|'''Sequencing'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|With trastuzumab
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62048-1/fulltext Del Mastro et al. 2015 (GIM2)]
−
|style="background-color:#91cf60"|Seems to have superior EFS
+
|style="background-color:#1a9851" |Phase III (C)
 +
|[[Complex_multipart_regimens#GIM2|See link]]
 +
|[[Complex_multipart_regimens#GIM2|See link]]
 
|-
 
|-
−
|No trastuzumab
+
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30319-4/fulltext Earl et al. 2017 (tAnGo)]
−
|style="background-color:#fc8d59"|Seems to have inferior EFS
+
| style="background-color:#1a9851" |Phase III (C)
 +
|TG
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
−
===References===
+
''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.''
−
# Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61964-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20113825 PubMed]
+
====Preceding treatment====
−
## '''Update:''' Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, Moliterni A, Vazquez F, Byakhov MJ, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Magazzù D, Heinzmann D, Steinseifer J, Valagussa P, Baselga J. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014 May;15(6):640-7. Epub 2014 Mar 20. Erratum in: Lancet Oncol. 2018 Dec;19(12):e667. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70080-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24657003 PubMed]
+
*INT 0148/CALGB 9344: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4 versus high-dose AC x 4 versus very-high-dose AC x 4
 +
*NSABP B-31, and ECOG E1199: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4
 +
*GIM2: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#EC_2|EC]] x 4 versus [[Breast_cancer#FEC_2|FEC]] x 4
 +
*tAnGo: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#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'''
  
−
==NSABP B-27==
+
===Variant #2, 225 mg/m<sup>2</sup> q3wk {{#subobject:b7a984|Variant=1}}===
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1, no taxane (Control)===
 
−
*[[Breast_cancer#AC|AC]] x 4, then [[surgery]]
 
−
===Arm 2, preoperative taxane (Experimental)===
 
−
*[[Breast_cancer#AC|AC]] x 4, [[Breast_cancer#Docetaxel_monotherapy|T (Taxotere)]] x 4, then [[surgery]]
 
−
===Arm 3, postoperative taxane (Experimental)===
 
−
*[[Breast_cancer#AC|AC]] x 4, then [[surgery]], then [[Breast_cancer#Docetaxel_monotherapy_2|T (Taxotere)]] x 4
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|AC, then [[surgery]]
+
|[http://jco.ascopubs.org/content/23/16/3686.long Mamounas et al. 2005 (NSABP B-28)]
−
| style="background-color:#d73027" |Inferior pCR rate
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
|-
+
|[[#Observation|Observation]]
−
|AC, then T, then [[surgery]]
+
| style="background-color:#1a9850" |Superior PFS
−
| style="background-color:#1a9850" |Superior pCR rate
 
−
|-
 
−
|AC, then [[surgery]], then T
 
−
| style="background-color:#d73027" |Inferior pCR rate
 
 
|-
 
|-
 
|}
 
|}
−
===References===
+
''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.''
−
# Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N; National Surgical Adjuvant Breast and Bowel Project Protocol B-27. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003 Nov 15;21(22):4165-74. Epub 2003 Oct 14. [https://ascopubs.org/doi/full/10.1200/JCO.2003.12.005 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14559892 PubMed]
+
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4
 +
====Chemotherapy====
 +
*[[Paclitaxel (Taxol)]] 225 mg/m<sup>2</sup> IV over 3 hours once on day 1
  
−
==NSABP B-30==
+
'''21-day cycle for 4 cycles'''
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1, AC -> T===
 
−
*[[Breast_cancer#AC_2|AC]] x 4, then [[Breast_cancer#Docetaxel_monotherapy_2|T (Taxotere)]] x 4
 
−
===Arm 2, AT===
 
−
*AT x 4
 
−
===Arm 3, ACT===
 
−
*[[Breast_cancer#TAC_.28Taxotere.29|ACT]] x 4
 
  
−
===Comparative efficacy===
 
−
====Comparison 1====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Schedule'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Sequential AC -> T
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|Concurrent ACT
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|}
 
−
====Comparison 2====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Schedule'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Sequential AC -> T
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|Concurrent AT
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
 
===References===
 
===References===
−
# Swain SM, Jeong JH, Geyer CE Jr, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff J, Vogel VG, Erban JK, Rastogi P, Livingston RB, Perez EA, Mamounas EP, Land SR, Ganz PA, Wolmark N. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med. 2010 Jun 3;362(22):2053-65. [https://www.nejm.org/doi/10.1056/NEJMoa0909638 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935316/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20519679 PubMed]
+
# '''INT 0148/CALGB 9344:''' Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. [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]
 +
<!-- Presented in abstract form at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003; interim results were presented at the 2000 NIH Consensus Development Conference, Bethesda, MD, November 1-3, 2000. -->
 +
# '''NSABP B-28:''' Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. [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 -->
 +
<!-- no pre-pub disclosed -->
 +
# '''NSABP B-31/NCCTG N9831:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa052122 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16236738 PubMed]
 +
## '''Update:''' Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011 Sep 1;29(25):3366-73. Epub 2011 Jul 18. [https://ascopubs.org/doi/full/10.1200/JCO.2011.35.0868 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164242/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21768458 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. [https://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. [https://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]
 +
## '''Update and HRQoL analysis:''' Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE Jr, Swain SM, Jeong JH, Fehrenbacher L, Gross HM, Brufsky AM, Flynn PJ, Wahl TA, Seay TE, Wade JL 3rd, Biggs DD, Atkins JN, Polikoff J, Zapas JL, Mamounas EP, Wolmark N. Long-term follow-up of cardiac function and quality of life for patients in NSABP protocol B-31/NRG Oncology: a randomized trial comparing the safety and efficacy of doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel and trastuzumab in patients with node-positive breast cancer with tumors overexpressing human epidermal growth factor receptor 2. J Clin Oncol. 2017 Dec 10;35(35):3942-3948. Epub 2017 Oct 26. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.1165 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721228/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29072977 PubMed]
 +
<!-- Presented in part at the San Antonio Breast Cancer Symposium, San Antonio, Texas, December 8–11, 2007, and the American Society of Clinical Oncology meeting, Chicago, June 1–4, 2005. -->
 +
# '''ECOG E1199:''' Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. [https://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]
 +
# '''GIM2:''' Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella (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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62048-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25740286 PubMed]
 +
# '''tAnGo:''' Earl HM, Hiller L, Howard HC, Dunn JA, Young J, Bowden SJ, McDermaid M, Waterhouse AK, Wilson G, Agrawal R, O'Reilly S, Bowman A, Ritchie DM, Goodman A, Hickish T, McAdam K, Cameron D, Dodwell D, Rea DW, Caldas C, Provenzano E, Abraham JE, Canney P, Crown JP, Kennedy MJ, Coleman R, Leonard RC, Carmichael JA, Wardley AM, Poole CJ; tAnGo trial collaborators. Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):755-769. Epub 2017 May 4. [https://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]
  
−
==NSABP B-38==
+
==PAF {{#subobject:5750af|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, sequential without gemcitabine (Control)===
+
PAF: '''<u>P</u>'''henylalanine mustard (Melphalan), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil
−
*[[Surgery]], then [[Breast_cancer#ddAC_2|ddAC]] x 4, then [[Breast_cancer#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|ddP]] x 4
+
===Regimen {{#subobject:763980|Variant=1}}===
−
===Arm 2, sequential with gemcitabine (Experimental)===
 
−
*[[Surgery]], then [[Breast_cancer#ddAC_2|ddAC]] x 4, then ddPG x 4
 
−
===Arm 3, concurrent===
 
−
*[[Surgery]], then [[Breast_cancer#TAC_.28Taxotere.29|TAC]] x 6
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Schedule'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Sequential (ddAC, then ddP)
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1989.7.5.572 Fisher et al. 1989 (NSABP B-11)]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
|-
+
|[[#PF|PF]]
−
|Sequential (ddAC, then ddPG)
+
| style="background-color:#91cf60" |Seems to have superior OS
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|Concurrent (TAC)
 
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Melphalan (Alkeran)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Fluorouracil (5-FU)]]
 
===References===
 
===References===
−
# Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. Epub 2013 Aug 12. [https://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] [https://www.ncbi.nlm.nih.gov/pubmed/23940225 PubMed]
+
# '''NSABP B-11:''' Fisher B, Redmond C, Wickerham DL, Bowman D, Schipper H, Wolmark N, Sass R, Fisher ER, Jochimsen P, Legault-Poisson S, Dimitrov N, Wolter J, Bornstein R, Elias EG, LiCalzi N, Paterson AHG, Sutherland CM. Doxorubicin-containing regimens for the treatment of stage II breast cancer: the National Surgical Adjuvant Breast and Bowel Project experience. J Clin Oncol. 1989 May;7(5):572-82. [https://ascopubs.org/doi/abs/10.1200/JCO.1989.7.5.572 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2651576 PubMed]
  
−
==NSABP B-40==
+
==PF {{#subobject:3a5d5f|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 - Control===
+
PF: '''<u>P</u>'''henylalanine mustard (Melphalan) & '''<u>F</u>'''luorouracil
−
*[[Breast_cancer#Docetaxel_monotherapy|T (Taxotere)]] x 4, then [[Breast_cancer#AC|AC]] x 4, then [[surgery]]
+
===Regimen {{#subobject:06f47d|Variant=1}}===
−
===Arm 2===
 
−
*[[Breast_cancer#Docetaxel_.26_Bevacizumab|T+Bev]], then [[Breast_cancer#AC_.26_Bevacizumab|AC+Bev]], then [[surgery]], then [[Breast_cancer#Bevacizumab_monotherapy|Bevacizumab]] x 10
 
−
===Arm 3===
 
−
*TX x 4, then [[Breast_cancer#AC|AC]] x 4, then [[surgery]]
 
−
===Arm 4===
 
−
*TX+Bev x 4, then [[Breast_cancer#AC_.26_Bevacizumab|AC+Bev]], then [[surgery]], then [[Breast_cancer#Bevacizumab_monotherapy|Bevacizumab]] x 10
 
−
===Arm 5===
 
−
*TG x 4, then [[Breast_cancer#AC|AC]] x 4, then [[surgery]]
 
−
===Arm 6===
 
−
*TG+Bev x 4, then [[Breast_cancer#AC_.26_Bevacizumab|AC+Bev]], then [[surgery]], then [[Breast_cancer#Bevacizumab_monotherapy|Bevacizumab]] x 10
 
−
===Comparative efficacy===
 
−
''This trial was analyzed using a 3 x 2 factorial design; primary endpoint was pathologic complete response (pCR) rate.''
 
−
====Addition of bevacizumab====
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|No bevacizumab (C)
+
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 Fisher et al. 1977 (NSABP B-07)]
−
|style="background-color:#fc8d59"|Seems to have inferior pCR rate
+
| style="background-color:#1a9851" |Phase III (E-esc)
 +
|[[#Melphalan_monotherapy|P]]
 +
| style="background-color:#91cf60" |Seems to have superior RFS
 
|-
 
|-
−
|Bevacizumab-based therapy (E)
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19800815)46:4%2B%3C1009::AID-CNCR2820461326%3E3.0.CO;2-H Fisher et al. 1980 (NSABP B-08)]
−
|style="background-color:#91cf60"|Seems to have superior pCR rate
+
| style="background-color:#1a9851" |Phase III (C)
 +
|PFM
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
−
|}
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198107023050101 Fisher et al. 1981 (NSABP B-09)]
−
====Addition of capecitabine or gemcitabine====
+
| style="background-color:#1a9851" |Phase III (C)
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
|[[#PFT|PFT]]
−
!'''Regimen'''
+
| style="background-color:#d73027" |Inferior RFS
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Docetaxel alone (C)
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1989.7.5.572 Fisher et al. 1989 (NSABP B-11)]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#1a9851" |Phase III (C)
 +
|[[#PAF|PAF]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
−
|TX or TG (E)
+
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%2819900715%2966%3A2%3C220%3A%3AAID-CNCR2820660205%3E3.0.CO%3B2-6 Fisher et al. 1990 (NSABP B-10)]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#1a9851" |Phase III (C)
 +
|PFCp
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
 +
''Note: Fisher et al. 1980 is more of a meta-analysis than a primary publication, but is to our knowledge the first manuscript to report the findings from NSABP B-08, which was a negative trial.''
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Melphalan (Alkeran)]]
 +
*[[Fluorouracil (5-FU)]]
 
===References===
 
===References===
−
# Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. [https://www.nejm.org/doi/full/10.1056/NEJMoa1111097 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401076/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22276821 PubMed]
+
# '''NSABP B-07:''' Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/194679 PubMed]
−
## '''Update:''' Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00041-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624323/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26272770 PubMed]
+
# '''NSABP B-08:''' Fisher B, Redmond C, Fisher ER. The contribution of recent NSABP clinical trials of primary breast cancer therapy to an understanding of tumor biology--an overview of findings. Cancer. 1980 Aug 15;46(4 Suppl):1009-25. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19800815)46:4%2B%3C1009::AID-CNCR2820461326%3E3.0.CO;2-H link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6994873 PubMed]
 +
# '''NSABP B-09:''' Fisher B, Redmond C, Brown A, Wolmark N, Wittliff J, Fisher ER, Plotkin D, Bowman D, Sachs S, Wolter J, Frelick R, Desser R, LiCalzi N, Geggie P, Campbell T, Elias EG, Prager D, Koontz P, Volk H, Dimitrov N, Gardner B, Lerner H, Shibata H. Treatment of primary breast cancer with chemotherapy and tamoxifen. N Engl J Med. 1981 Jul 2;305(1):1-6. [https://www.nejm.org/doi/full/10.1056/NEJM198107023050101 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7015139 PubMed]
 +
## '''Update:''' Fisher B, Redmond C, Brown A, Fisher ER, Wolmark N, Bowman D, Plotkin D, Wolter J, Bornstein R, Legault-Poisson S, Saffer EA. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial. J Clin Oncol. 1986 Apr;4(4):459-71. [https://ascopubs.org/doi/abs/10.1200/JCO.1986.4.4.459 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2856857 PubMed]
 +
## '''Update:''' Fisher B, Brown A, Wolmark N, Redmond C, Wickerham DL, Wittliff J, Dimitrov N, Legault-Poisson S, Schipper H, Prager D. Prolonging tamoxifen therapy for primary breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial. Ann Intern Med. 1987 May;106(5):649-54. [http://annals.org/aim/article-abstract/701830/prolonging-tamoxifen-therapy-primary-breast-cancer-findings-from-national-surgical link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3551710 PubMed]
 +
# '''NSABP B-11:''' Fisher B, Redmond C, Wickerham DL, Bowman D, Schipper H, Wolmark N, Sass R, Fisher ER, Jochimsen P, Legault-Poisson S, Dimitrov N, Wolter J, Bornstein R, Elias EG, LiCalzi N, Paterson AHG, Sutherland CM. Doxorubicin-containing regimens for the treatment of stage II breast cancer: the National Surgical Adjuvant Breast and Bowel Project experience. J Clin Oncol. 1989 May;7(5):572-82. [https://ascopubs.org/doi/abs/10.1200/JCO.1989.7.5.572 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2651576 PubMed]
 +
# '''NSABP B-10:''' Fisher B, Brown A, Wolmark N, Fisher ER, Redmond C, Wickerham DL, Margolese R, Dimitrov N, Pilch Y, Glass A, Sutherland C, Foster R. Evaluation of the worth of corynebacterium parvum in conjunction with chemotherapy as adjuvant treatment for primary breast cancer: eight-year results from the National Surgical Adjuvant Breast and Bowel Project B-10. Cancer. 1990 Jul 15;66(2):220-7. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%2819900715%2966%3A2%3C220%3A%3AAID-CNCR2820660205%3E3.0.CO%3B2-6 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2196108 PubMed]
  
−
==NSAS BC-02==
+
==PFT {{#subobject:1cb87f|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 - Control===
+
PFT: '''<u>P</u>'''henylalanine mustard (Melphalan), 5-'''<u>F</u>'''luorouracil, '''<u>T</u>'''amoxifen
−
*[[Surgery]], [[Breast_cancer#AC_2|AC]] x 4, then [[Breast_cancer#Docetaxel_monotherapy_2|T (Taxotere)]] x 4
+
===Regimen {{#subobject:c084f5|Variant=1}}===
−
===Arm 2 - Control===
 
−
*[[Surgery]], [[Breast_cancer#AC_2|AC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T (Taxol)]] x 4
 
−
===Arm 3===
 
−
*[[Surgery]], then docetaxel x 8
 
−
===Arm 4===
 
−
*[[Surgery]], then paclitaxel x 8
 
−
===Comparative efficacy===
 
−
''This trial was analyzed using a 2 x 2 factorial design.''
 
−
====Use of AC====
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|AC-containing
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198107023050101 Fisher et al. 1981 (NSABP B-09)]
−
|style="background-color:#ffffbf"|Inconclusive whether non-inferior
+
| style="background-color:#1a9851" |Phase III (E-RT-esc)
−
|-
+
|[[#PF|PF]]
−
|AC-free
+
| style="background-color:#1a9850" |Superior RFS
−
|style="background-color:#ffffbf"|Inconclusive whether non-inferior
 
−
|-
 
−
|}
 
−
====Taxane====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Docetaxel
+
|rowspan=2|[https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.6.1005 Fisher et al. 1990 (NSABP B-16)]
−
| style="background-color:#91cf60" |Seems to have superior OS
+
|rowspan=2 style="background-color:#1a9851" |Phase III (E-esc)
 +
|1. [[#ACT|ACT]]
 +
| style="background-color:#d3d3d3" |Not reported
 
|-
 
|-
−
|Paclitaxel (q3wk)
+
|2. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]]
−
| style="background-color:#fc8d59" |Seems to have inferior OS
+
| style="background-color:#91cf60" |Seems to have superior DDFS
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Breast_cancer_surgery|Surgery]]
 +
====Chemotherapy====
 +
*[[Melphalan (Alkeran)]]
 +
*[[Fluorouracil (5-FU)]]
 +
====Hormonotherapy====
 +
*[[Tamoxifen (Nolvadex)]]
 +
 
===References===
 
===References===
−
# Watanabe T, Kuranami M, Inoue K, Masuda N, Aogi K, Ohno S, Iwata H, Mukai H, Uemura Y, Ohashi Y. Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study. Cancer. 2017 Mar 1;123(5):759-768. Epub 2017 Jan 12. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.30421/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28081304 PubMed]
+
# '''NSABP B-09:''' Fisher B, Redmond C, Brown A, Wolmark N, Wittliff J, Fisher ER, Plotkin D, Bowman D, Sachs S, Wolter J, Frelick R, Desser R, LiCalzi N, Geggie P, Campbell T, Elias EG, Prager D, Koontz P, Volk H, Dimitrov N, Gardner B, Lerner H, Shibata H. Treatment of primary breast cancer with chemotherapy and tamoxifen. N Engl J Med. 1981 Jul 2;305(1):1-6. [https://www.nejm.org/doi/full/10.1056/NEJM198107023050101 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7015139 PubMed]
 +
## '''Update:''' Fisher B, Redmond C, Brown A, Fisher ER, Wolmark N, Bowman D, Plotkin D, Wolter J, Bornstein R, Legault-Poisson S, Saffer EA. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial. J Clin Oncol. 1986 Apr;4(4):459-71. [https://ascopubs.org/doi/abs/10.1200/JCO.1986.4.4.459 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2856857 PubMed]
 +
## '''Update:''' Fisher B, Brown A, Wolmark N, Redmond C, Wickerham DL, Wittliff J, Dimitrov N, Legault-Poisson S, Schipper H, Prager D. Prolonging tamoxifen therapy for primary breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial. Ann Intern Med. 1987 May;106(5):649-54. [http://annals.org/aim/article-abstract/701830/prolonging-tamoxifen-therapy-primary-breast-cancer-findings-from-national-surgical link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3551710 PubMed]
 +
# '''NSABP B-16:''' Fisher B, Redmond C, Legault-Poisson S, Dimitrov NV, Brown AM, Wickerham DL, Wolmark N, Margolese RG, Bowman D, Glass AG, Kardinal CG, Robidoux A, Jochimsen P, Cronin W, Deutsch M, Fisher ER, Myers DB, Hoehn JL. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990 Jun;8(6):1005-18. [https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.6.1005 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2189950 PubMed]
 +
## '''Pooled update:''' Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. [https://ascopubs.org/doi/full/10.1200/JCO.2004.01.042 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15452182 PubMed]
  
−
==PREPARE==
+
==Placebo==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, control===
+
===Regimen===
−
*[[Breast_cancer#EC|EC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T (Taxol)]] x 4, then [[Surgery#Breast_cancer_surgery|surgery]]
 
−
===Arm 2, experimental===
 
−
*ddE x 3, then ddT (Taxol) x 3, then CMF x 3, then [[Surgery#Breast_cancer_surgery|surgery]]
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
|-
+
!style="width: 25%"|Comparator
−
|Control
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
| style="background-color:#ffffbf" |Seems not superior
 
 
|-
 
|-
−
|Experimental
+
|[https://www.nejm.org/doi/full/10.1056/NEJM197501162920301 Fisher et al. 1975 (NSABP B-05)]
−
| style="background-color:#ffffbf" |Seems not superior
+
|style="background-color:#1a9851"|Phase III (C)
 +
|[[#Melphalan_monotherapy|Melphalan]]
 +
|style="background-color:#fee08b" |Might have inferior DFS (*)
 
|-
 
|-
 
|}
 
|}
 +
''No active antineoplastic treatment after mastectomy. Used as a comparator arm, historically. Reported efficacy for NSABP B-05 is based on the 1986 update.''
 +
====Preceding treatment====
 +
*[[Surgery#Mastectomy|Mastectomy]]
 
===References===
 
===References===
−
# Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C, Lück HJ, Stickeler E, Urbaczyk H, Liedtke B, Beckmann MW, Salat C, Harbeck N, Müller V, Schmidt M, Hasmüller S, Lenhard M, Nekljudova V, Lebeau A, Loibl S, Fasching PA; Arbeitsgemeinschaft Gynäkologische Onkologie PREPARE investigators. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer--outcome on prognosis. Ann Oncol. 2011 Sep;22(9):1999-2006. Epub 2011 Mar 7. [https://academic.oup.com/annonc/article/22/9/1999/211410 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21382868 PubMed]
+
# '''NSABP B-05:''' Fisher B, Carbone P, Economou SG, Frelick R, Glass A, Lerner H, Redmond C, Zelen M, Band P, Katrych DL, Wolmark N, Fisher ER. 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer: a report of early findings. N Engl J Med. 1975 Jan 16;292(3):117-22. [https://www.nejm.org/doi/full/10.1056/NEJM197501162920301 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1105174 PubMed]
 +
## '''Update:''' Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197706)39:6%3C2883::AID-CNCR2820390676%3E3.0.CO;2-9/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/194679 PubMed]
 +
## '''Update:''' Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986 Jun;4(6):929-41. [https://ascopubs.org/doi/full/10.1200/JCO.1986.4.6.929 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3519883 PubMed]
  
−
==Recht et al. 1996==
+
==PT {{#subobject:c08464|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, chemo first===
+
PT: '''<u>P</u>'''rednisone & '''<u>T</u>'''amoxifen
−
*[[Surgery#Lumpectomy|Lumpectomy]], then [[Breast_cancer_-_historical#CAMFP|CAMFP]], then RT
+
===Regimen {{#subobject:2fc709|Variant=1}}===
−
===Arm 2, RT first===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
*[[Surgery#Lumpectomy|Lumpectomy]], then RT, then [[Breast_cancer_-_historical#CAMFP|CAMFP]]
+
!style="width: 25%"|Study
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
!style="width: 25%"|Comparator
−
!style="width: 50%"|'''anti-HER2 medication'''
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
!style="width: 50%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
|-
 +
|rowspan = 2|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS III)]
 +
|rowspan = 2 style="background-color:#1a9851" |Phase III (E-esc)
 +
|1. [[#CMFPT|CMFPT]]
 +
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
|-
 
|-
−
|Chemo first
+
|2. [[#Observation|Observation]]
−
| style="background-color:#91cf60" |Seems to have superior MFS
+
| style="background-color:#1a9850" |Superior DFS
 
|-
 
|-
−
|RT first
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS IV)]
−
| style="background-color:#fc8d59" |Seems to have inferior MFS
+
|style="background-color:#1a9851" |Phase III (E-esc)
 +
|[[#Observation|Observation]]
 +
| style="background-color:#91cf60" |Seems to have superior DFS
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Mastectomy|Mastectomy]]
 +
====Hormonotherapy====
 +
*[[Prednisone (Sterapred)]]
 +
*[[Tamoxifen (Nolvadex)]]
 +
 
===References===
 
===References===
−
# Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, Shulman LN, Harris JR. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996 May 23;334(21):1356-61. [https://www.nejm.org/doi/full/10.1056/NEJM199605233342102 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8614420 PubMed]
+
# '''LBCS III/IV:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. [https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6144974 PubMed]
  
−
==SB3-G31-BC==
+
==TMF {{#subobject:c08464|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, trastuzumab (control)===
+
TMF: '''<u>T</u>'''hiotepa, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
−
*[[Breast_cancer,_HER2-positive#TH_.28Taxotere.29|TH]] x 4, then [[Breast_cancer,_HER2-positive#FEC_.26_H|FEC & H]] x 4, then [[surgery]], then [[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy_2|adjuvant trastuzumab]]
+
===Regimen {{#subobject:2fc709|Variant=1}}===
−
===Arm 2, SB3 (experimental trastuzumab biosimilar)===
+
{| class="wikitable" style="width: 50%; text-align:center;"  
−
*Same schedule with SB3 instead of trastuzumab
+
!style="width: 25%"|Study
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!style="width: 50%"|'''anti-HER2 medication'''
 
−
!style="width: 50%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
 
|-
 
|-
−
|Trastuzumab
+
|[https://academic.oup.com/annonc/article-abstract/5/7/591/206435 Semiglazov et al. 1994]
−
|style="background-color:#eeee01"|Equivalent pCR rate
+
| style="background-color:#91cf61" |Non-randomized portion of RCT
−
|-
 
−
|SB3 (trastuzumab biosimilar)
 
−
|style="background-color:#eeee01"|Equivalent pCR rate
 
 
|-
 
|-
 
|}
 
|}
 +
====Preceding treatment====
 +
*[[Surgery#Mastectomy|Mastectomy]]
 +
====Chemotherapy====
 +
*[[Thiotepa (Thioplex)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 
===References===
 
===References===
−
# Pivot X, Bondarenko I, Nowecki Z, Dvorkin M, Trishkina E, Ahn JH, Vinnyk Y, Im SA, Sarosiek T, Chatterjee S, Wojtukiewicz MZ, Moiseyenko V, Shparyk Y, Bello M 3rd, Semiglazov V, Song S, Lim J. Phase III, randomized, double-blind study comparing the efficacy, safety, and immunogenicity of SB3 (trastuzumab biosimilar) and reference trastuzumab in patients treated with neoadjuvant therapy for human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2018 Apr 1;36(10):968-974. Epub 2018 Jan 26. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.0126 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29373094 PubMed]
+
# Semiglazov VF, Topuzov EE, Bavli JL, Moiseyenko VM, Ivanova OA, Seleznev IK, Orlov AA, Barash NY, Golubeva OM, Chepic OF. Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer. Ann Oncol. 1994 Sep;5(7):591-5. [https://academic.oup.com/annonc/article-abstract/5/7/591/206435 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7993833 PubMed]
  
−
==SBG 9401==
+
=Metastatic disease, all lines of therapy=
 +
==Aminoglutethimide monotherapy {{#subobject:821a2c|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (control)===
+
===Regimen {{#subobject:f62b32|Variant=1}}===
−
*[[Surgery]], then [[Breast_cancer#FEC_2|FEC]] x 2, then HD-FEC x 1, then [[Breast_cancer_-_historical#CTCb.2C_then_auto_HSCT|CTCb with auto HSCT]]
 
−
===Arm 2 (experimental)===
 
−
*Tailored FEC x 6
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Control
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(78)92759-9/fulltext Smith et al. 1978]
−
| style="background-color:#fc8d59" |Seems to have inferior RFS
+
| style="background-color:#91cf61" |Non-randomized
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|Experimental
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198109033051003 Santen et al. 1981]
−
| style="background-color:#91cf60" |Seems to have superior RFS
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 +
|Bilateral adrenalectomy
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
|-
 
|-
−
|}
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)90596-8/fulltext Stuart-Harris et al. 1984]
−
===References===
+
| style="background-color:#91cf61" |Phase II
−
# Bergh J, Wiklund T, Erikstein B, Lidbrink E, Lindman H, Malmström P, Kellokumpu-Lehtinen P, Bengtsson NO, Söderlund G, Anker G, Wist E, Ottosson S, Salminen E, Ljungman P, Holte H, Nilsson J, Blomqvist C, Wilking N; Scandinavian Breast Group 9401 study. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Lancet. 2000 Oct 21;356(9239):1384-91. Erratum in: Lancet 2000 Dec 23-30;356(9248):2196. [https://www.sciencedirect.com/science/article/pii/S0140673600028415 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/11052580 PubMed]
+
| style="background-color:#d3d3d3" |
−
 
+
| style="background-color:#d3d3d3" |
−
==SWOG-8814==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 Canney et al. 1988]
−
|}
+
|style="background-color:#1a9851"|Phase III (E-switch-ic)
−
===Arm 1 (Control)===
+
|[[#Medroxyprogesterone_monotherapy|MPA]]
−
*[[Surgery]], then [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|tamoxifen]] x 5 y
+
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
−
===Arm 2, CAF-T (Experimental)===
 
−
*[[Surgery]], then [[Breast_cancer#FAC_2|CAF]] x 6, then [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|tamoxifen]] x 5 y
 
−
===Arm 3, CAFT (Experimental)===
 
−
*[[Surgery]], then CAFT
 
−
===Comparative efficacy===
 
−
====Comparison 1====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Design'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|No chemotherapy
+
|[https://link.springer.com/article/10.1007/BF01810736 Lundgren et al. 1989]
−
| style="background-color:#fee08b" |Might have inferior OS
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 +
|[[#Megestrol_monotherapy|Megestrol]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
|-
 
|-
−
|With chemotherapy
+
|[https://link.springer.com/article/10.1007/BF01961246 Garcia-Giralt et al. 1992]
−
| style="background-color:#d9ef8b" |Might have superior OS
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 +
|[[#Medroxyprogesterone_monotherapy|MPA]]
 +
| style="background-color:#91cf60" |Seems to have superior TTP
 
|-
 
|-
−
|}
+
|[https://www.ncbi.nlm.nih.gov/pubmed/8135469 Robustelli della Cuna et al. 1993]
−
====Comparison 2====
+
| style="background-color:#1a9851" |Phase III (C)
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]; higher-dose
−
!'''Timing'''
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Concurrent (CAFT)
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19940115)73:2%3C354::AID-CNCR2820730220%3E3.0.CO;2-J Gale et al. 1994]
−
| style="background-color:#fee08b" |Might have inferior DFS
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
−
|-
+
|1. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]<br> 2. Bilateral adrenalectomy
−
|Sequential (CAF-T)
+
| style="background-color:#ffffbf" |Did not meet primary endpoints of DOR/TTF/OS
−
| style="background-color:#d9ef8b" |Might have superior DFS
 
 
|-
 
|-
 
|}
 
|}
−
===References===
+
====Hormonotherapy====
−
# Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, Cobau CD, Levine EG, Ingle JN, Pritchard KI, Lichter AS, Schneider DJ, Abeloff MD, Henderson IC, Muss HB, Green SJ, Lew D, Livingston RB, Martino S, Osborne CK; Breast Cancer Intergroup of North America. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Dec 19;374(9707):2055-2063. Epub 2009 Dec 10. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61523-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140679/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20004966 PubMed]
+
*[[Aminoglutethimide (Cytadren)]]
  
−
==TACT==
+
====Supportive medications====
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
*[[Hydrocortisone (Cortef)]]
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1 (Experimental)===
 
−
*[[Surgery]], then [[Breast_cancer#FEC_2|FEC]] x 4, then [[#Docetaxel_monotherapy_2|D]] x 4
 
−
===Arm 2 (Control)===
 
−
*[[Surgery]], then [[Breast_cancer#FEC_2|FEC]] x 8
 
−
===Arm 3 (Control)===
 
−
*[[Surgery]], then [[Breast_cancer#Epirubicin_monotherapy|E]] x 4, then [[Breast_cancer#CMF|CMF]] x 4
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Experimental (with docetaxel)
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|Standard (no docetaxel)
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|}
 
 
===References===
 
===References===
−
# Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. [https://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]
+
# Smith IE, Fitzharris BM, McKinna JA, Fahmy DR, Nash AG, Neville AM, Gazet JC, Ford HT, Powles TJ. Aminoglutethimide in treatment of metastatic breast carcinoma. Lancet. 1978 Sep 23;2(8091):646-9. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(78)92759-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/80576 PubMed]
 +
# Santen RJ, Worgul TJ, Samojlik E, Interrante A, Boucher AE, Lipton A, Harvey HA, White DS, Smart E, Cox C, Wells SA. A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer. N Engl J Med. 1981 Sep 3;305(10):545-51. [https://www.nejm.org/doi/full/10.1056/NEJM198109033051003 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7019703 PubMed]
 +
# Stuart-Harris R, Dowsett M, Bozek T, McKinna JA, Gazet JC, Jeffcoate SL, Kurkure A, Carr L, Smith IE. Low-dose aminoglutethimide in treatment of advanced breast cancer. Lancet. 1984 Sep 15;2(8403):604-7. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)90596-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6147642 PubMed]
 +
# Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, Spooner D. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. J Natl Cancer Inst. 1988 Sep 21;80(14):1147-51. [https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2970555 PubMed]
 +
# Lundgren S, Gundersen S, Klepp R, Lønning PE, Lund E, Kvinnsland S. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Res Treat. 1989 Nov;14(2):201-6. [https://link.springer.com/article/10.1007/BF01810736 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2690972 PubMed]
 +
# Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P, Fumoleau P, Gorins A, Guerin D, Guerin R, Maillart P, Mauriac L, May-Levin F, Metz R, Namer M, Olivier JP, Pommatau E, Pouillart P, Pujade-Lauraine E, Rouesse J, Serrou B, Vitse M, Zylberait D. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Res Treat. 1992;24(2):139-45. [https://link.springer.com/article/10.1007/BF01961246 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8443401 PubMed]
 +
# Robustelli della Cuna G, Pannuti F, Martoni A, Camaggi CM, Strocchi E, Da Prada GA, Tanneberger S; Italian Cooperative Group. Aminoglutethimide in advanced breast cancer: prospective, randomized comparison of two dose levels. Anticancer Res. 1993 Nov-Dec;13(6B):2367-71. [https://www.ncbi.nlm.nih.gov/pubmed/8135469 PubMed]
 +
# Gale KE, Andersen JW, Tormey DC, Mansour EG, Davis TE, Horton J, Wolter JM, Smith TJ, Cummings FJ. Hormonal treatment for metastatic breast cancer: an Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen. Cancer. 1994 Jan 15;73(2):354-61. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19940115)73:2%3C354::AID-CNCR2820730220%3E3.0.CO;2-J link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8293400 PubMed]
  
−
==TACT2==
+
==CAMF {{#subobject:4b99b8|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Experimental)===
+
CAMF: '''<u>C</u>'''yclophosphamide,  '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
−
*ddE, then [[Breast_cancer#Capecitabine_monotherapy|capecitabine]]
+
<br>AFCM: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate
−
===Arm 2 (Experimental)===
+
===Regimen {{#subobject:7c9b85|Variant=1}}===
−
*ddE, then [[Breast_cancer#CMF|CMF]]
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
===Arm 3 (Experimental)===
+
!style="width: 25%"|Study
−
*[[Breast_cancer#Epirubicin_monotherapy|E]], then [[Breast_cancer#Capecitabine_monotherapy|capecitabine]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
===Arm 4 (Control)===
+
!style="width: 25%"|Comparator
−
*[[Breast_cancer#Epirubicin_monotherapy|E]], then [[Breast_cancer#CMF|CMF]]
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
===Comparative efficacy===
 
−
*Analyzed using a 2 x 2 factorial design
 
−
====Comparison 1====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Dose density of epirubicin'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Dose-dense (q2wk)
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197806)41:6%3C2078::AID-CNCR2820410602%3E3.0.CO;2-Q Tranum et al. 1978]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#1a9851" |Randomized (E-esc)
 +
|1. AF<br> 2. [[Breast_cancer#FAC_3|FAC]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
|-
 
|-
−
|Standard (q3wk)
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D Bezwoda et al. 1979]
−
|style="background-color:#ffffbf"|Seems not superior
+
|style="background-color:#1a9851" |Randomized (E-switch-ic)
 +
|[[#CMFV|CMFV]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
|-
 
|-
−
|}
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1984.2.1.28 Lippman et al. 1984]
−
====Comparison 2====
+
| style="background-color:#1a9851" |Randomized (C)
−
{| class="wikitable" style="width: 100%; text-align:center;"
+
|CAMFTP
−
!'''Capecitabine vs. CMF'''
+
| style="background-color:#ffffbf" |Seems not superior
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Capecitabine
 
−
|style="background-color:#eeee01"|Non-inferior TTR
 
−
|-
 
−
|CMF
 
−
|style="background-color:#eeee01"|Non-inferior TTR
 
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 +
 
===References===
 
===References===
−
# Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, Agrawal R, Banerji J, Bertelli G, Bloomfield D, Brunt AM, Earl H, Ellis P, Gaunt C, Gillman A, Hearfield N, Laing R, Murray N, Couper N, Stein RC, Verrill M, Wardley A, Barrett-Lee P, Bliss JM; TACT2 Investigators. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2017 Jul;18(7):929-945. Epub 2017 Jun 7. [https://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] [https://www.ncbi.nlm.nih.gov/pubmed/28600210 PubMed]
+
# Tranum B, Hoogstraten B, Kennedy A, Vaughn CB, Samal B, Thigpen T, Rivkin S, Smith F, Palmer RL, Costanzi J, Tucker WG, Wilson H, Maloney TR. Adriamycin in combination for the treatment of breast cancer: a Southwest Oncology Group study. Cancer. 1978 Jun;41(6):2078-83. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197806)41:6%3C2078::AID-CNCR2820410602%3E3.0.CO;2-Q link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/657081 PubMed]
 +
# Bezwoda WR, de Moor NG, Derman D, Lange M, Saner R, Dando R. Combination chemotherapy of metastatic breast cancer: a randomized trial comparing the use of adriamycin to that of Vinblastine. Cancer. 1979 Aug;44(2):392-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/383254 PubMed]
 +
# Lippman ME, Cassidy J, Wesley M, Young RC. A randomized attempt to increase the efficacy of cytotoxic chemotherapy in metastatic breast cancer by hormonal synchronization. J Clin Oncol. 1984 Jan;2(1):28-36. [https://ascopubs.org/doi/abs/10.1200/JCO.1984.2.1.28 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6321686 PubMed]
  
−
==TEAM==
+
==CAF & MPA {{#subobject:6c7ff9|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, monotherapy (Control)===
+
CAF & MPA: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil, '''<u>M</u>'''edroxy'''<u>P</u>'''rogesterone '''<u>A</u>'''cetate
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5y
+
===Regimen {{#subobject:b2ce67|Variant=1}}===
−
===Arm 2, sequential (Experimental)===
 
−
*[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 2.5-3y, then [[Breast_cancer,_ER-positive#Exemestane_monotherapy|Exemestane]] x 2-2.5y
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Tamoxifen x 5y
+
|[https://www.ejcancer.com/article/0959-8049(94)90123-6/pdf Tominaga et al. 1994]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
|-
+
|[[Breast_cancer#FAC_3|CAF]]
−
|Tamoxifen x 2.5-3y, then Exemestane x 2-2.5y
+
| style="background-color:#91cf60" |Seems to have superior ORR
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Fluorouracil (5-FU)]]
 +
====Hormonotherapy====
 +
*[[Medroxyprogesterone (MPA)]]
 
===References===
 
===References===
−
# 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. [https://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]
+
# Tominaga T, Abe O, Ohshima A, Hayasaka H, Uchino J, Abe R, Enomoto K, Izuo M, Watanabe H, Takatani O, Yoshida M, Sakai K, Koyama H, Hattori T, Senoo T, Monden Y, Nomura Y. Comparison of chemotherapy with or without medroxyprogesterone acetate for advanced or recurrent breast cancer. Eur J Cancer. 1994;30A(7):959-64. [https://www.ejcancer.com/article/0959-8049(94)90123-6/pdf link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7946592 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. [https://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]
 
  
−
==TRYPHAENA==
+
==CAFVP {{#subobject:918bda|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm A===
+
CAFVP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
−
*FEC & HP x 3, then [[Breast_cancer,_HER2-positive#THP_.28Taxotere.29|THP]] x 3, then [[surgery]]
+
===Regimen {{#subobject:e01caf|Variant=1}}===
−
===Arm B===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
*[[Breast_cancer#FEC|FEC]] x 3, then [[Breast_cancer,_HER2-positive#THP_.28Taxotere.29|THP]] x 3, then [[surgery]]
+
!style="width: 25%"|Study
−
===Arm C===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
*[[Breast_cancer,_HER2-positive#TCHP_.28Taxotere.29|TCHP]] x 6, then [[surgery]]
+
!style="width: 25%"|Comparator
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
''Note: this was a cardiac safety study; efficacy findings are not reported.''
 
−
===References===
 
−
# '''TRYPHAENA:''' Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. [http://annonc.oxfordjournals.org/content/24/9/2278.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23704196 PubMed]
 
−
 
 
−
=Cervical cancer=
 
−
==NOGGO-AGO==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 Muss et al. 1978]
−
|}
+
|style="background-color:#1a9851" |Phase III (E-switch-ic)
−
===Arm 1 (Control)===
+
|[[#CMFVP_2|CMFVP]]
−
*[[Surgery]], then [[Cervical_cancer#Carboplatin_.26_Ifosfamide|adjuvant Carboplatin & Ifosfamide]] x 4, then [[Cervical_cancer#Radiation_therapy_2|EBRT]]
+
| style="background-color:#d9ef8b" |Might have superior OS
−
===Arm 2 (Experimental)===
 
−
*[[Surgery]], then adjuvant Carboplatin, Ifosfamide, Erythropoietin alfa, then EBRT & Erythropoietin alfa
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|No EPO
+
|rowspan=2|[https://ascopubs.org/doi/abs/10.1200/JCO.1987.5.10.1523 Aisner et al. 1987]
−
|style="background-color:#fee08b"|Might have inferior RFS
+
|rowspan=2 style="background-color:#1a9851" |Phase III (E-esc)
 +
|1. [[Breast_cancer#FAC_3|CAF]]
 +
| style="background-color:#d3d3d3" |Not reported
 
|-
 
|-
−
|With EPO
+
|2. [[Breast_cancer#CMF_2|CMF]]
−
|style="background-color:#d9ef8b"|Might have superior RFS
+
| style="background-color:#1a9850" |Superior ORR
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Fluorouracil (5-FU)]]
 +
*[[Vincristine (Oncovin)]]
 +
====Hormonotherapy====
 +
*[[Prednisone (Sterapred)]]
 
===References===
 
===References===
−
# Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. [https://ascopubs.org/doi/full/10.1200/JCO.2010.30.4899 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21860000 PubMed]
+
# Muss HB, White DR, Richards F 2nd, Cooper MR, Stuart JJ, Jackson DV, Rhyne L, Spurr CL. Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial. Cancer. 1978 Nov;42(5):2141-8. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/363253 PubMed]
 +
# Aisner J, Weinberg V, Perloff M, Weiss R, Perry M, Korzun A, Ginsberg S, Holland JF; Cancer and Leukemia Group B. Chemotherapy versus chemoimmunotherapy (CAF v CAFVP v CMF each +/- MER) for metastatic carcinoma of the breast: a CALGB study. J Clin Oncol. 1987 Oct;5(10):1523-33. [https://ascopubs.org/doi/abs/10.1200/JCO.1987.5.10.1523 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3655855 PubMed]
  
−
=[[Colon cancer|Colorectal cancer]]=
+
==CFP {{#subobject:ba429d|Regimen=1}}==
−
==CAIRO==
 
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, sequential single agent (Control)===
+
CFP: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
−
*[[Colon_cancer#Capecitabine_monotherapy_2|First-line capecitabine]], then [[Colon_cancer#Irinotecan_monotherapy_2|second-line irinotecan]], then [[Colon_cancer#CapeOx_4|third-line CapeOx]]
+
===Regimen {{#subobject:26519a|Variant=1}}===
−
===Arm 2, sequential combinations (Experimental)===
 
−
*[[Colon_cancer#CAPIRI|First-line CAPIRI]], then [[Colon_cancer#CapeOx_3|second-line CapeOx]]
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Approach'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Sequential single agent
+
|[https://ascopubs.org/doi/10.1200/JCO.1984.2.11.1260 Creagan et al. 1984]
−
| style="background-color:#ffffbf" |Seems not superior
+
| style="background-color:#1a9851" |Phase III (C)
 +
|CAP, then CFP
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 +
|-
 +
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O Rosner et al. 1987]
 +
| style="background-color:#1a9851" |Phase III (E-esc)
 +
|1. [[Breast_cancer#AC_3|CA]]<br> 2. [[#CMFVP_2|CMFVP]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
−
|Sequential combinations
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F Marschke et al. 1989]
−
| style="background-color:#ffffbf" |Seems not superior
+
| style="background-color:#1a9851" |Phase III (C)
 +
|[[#CMFP_2|CMFP]]
 +
| style="background-color:#fee08b" |Might have inferior ORR
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Fluorouracil (5-FU)]]
 +
====Hormonotherapy====
 +
*[[Prednisone (Sterapred)]]
 +
 
===References===
 
===References===
−
# Koopman M, Antonini NF, Douma J, Wals J, Honkoop AH, Erdkamp FL, de Jong RS, Rodenburg CJ, Vreugdenhil G, Loosveld OJ, van Bochove A, Sinnige HA, Creemers GM, Tesselaar ME, Slee PHTJ, Werter MJ, Mol L, Dalesio O, Punt CJ. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet. 2007 Jul 14;370(9582):135-142. [https://www.thelancet.com/journals/lancet/article/PIIS0140673607610861/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17630036 PubMed]
+
# Creagan ET, Green SJ, Ahmann DL, Ingle JN, Edmonson JH, Marschke RF Jr. A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer. J Clin Oncol. 1984 Nov;2(11):1260-5. [https://ascopubs.org/doi/10.1200/JCO.1984.2.11.1260 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6387059 PubMed]
 +
# Rosner D, Nemoto T, Lane WW. A randomized study of intensive versus moderate chemotherapy programs in metastatic breast cancer. Cancer. 1987 Mar 1;59(5):874-83. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3815266 PubMed]
 +
# Marschke RF Jr, Ingle JN, Schaid DJ, Krook JE, Mailliard JA, Cullinan SA, Pfeifle DM, Votava HJ, Ebbert LP, Windschitl HE. Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer. Cancer. 1989 May 15;63(10):1931-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2649221 PubMed]
  
−
==FFCD 2000-05==
+
==Chlorambucil & Prednisolone {{#subobject:2cde9a|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, sequential (Control)===
+
===Regimen {{#subobject:0044a9|Variant=1}}===
−
*[[Colon_cancer#Fluorouracil_.26_Folinic_acid_2|First-line sLV5FU2]], then [[Colon_cancer#mFOLFOX6_4|second-line mFOLFOX6]], then [[Colon_cancer#FOLFIRI_4|third-line FOLFIRI]]
+
{| class="wikitable" style="width: 50%; text-align:center;"  
−
===Arm 2, combination (Experimental)===
+
!style="width: 25%"|Study
−
*[[Colon_cancer#mFOLFOX6_3|First-line mFOLFOX6]], then [[Colon_cancer#FOLFIRI_3|second-line FOLFIRI]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Approach'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
![[Levels_of_Evidence#Toxicity|Toxicity]]
 
−
|-
 
−
|Sequential
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
| style="background-color:#1a9850" |Less toxic
 
 
|-
 
|-
−
|Combination
+
|[https://jamanetwork.com/journals/jama/article-abstract/1163685 Freckman et al. 1964]
−
| style="background-color:#ffffbf" |Seems not superior
+
| style="background-color:#91cf61" |Non-randomized
−
| style="background-color:#d73027" |More toxic
 
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Chlorambucil (Leukeran)]]
 +
====Hormonotherapy====
 +
*[[Prednisolone (Millipred)]]
 
===References===
 
===References===
−
# Ducreux M, Malka D, Mendiboure J, Etienne PL, Texereau P, Auby D, Rougier P, Gasmi M, Castaing M, Abbas M, Michel P, Gargot D, Azzedine A, Lombard-Bohas C, Geoffroy P, Denis B, Pignon JP, Bedenne L, Bouché O; Fédération Francophone de Cancérologie Digestive (FFCD) 2000–05 Collaborative Group. Sequential versus combination chemotherapy for the treatment of advanced colorectal cancer (FFCD 2000-05): an open-label, randomised, phase 3 trial. Lancet Oncol. 2011 Oct;12(11):1032-44. Epub 2011 Sep 6. [https://www.thelancet.com/journals/lancetonc/article/PIIS1470204511701991/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21903473 PubMed]
+
# Freckman HA, Fry HL, Mendez FL, Maurer ER. Chlorambucil-prednisolone therapy for disseminated breast carcinoma. JAMA. 1964 Jul 6;189:23-6. [https://jamanetwork.com/journals/jama/article-abstract/1163685 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14149018 PubMed]
  
−
=[[Diffuse large B-cell lymphoma]]=
+
==CHUT, then auto HSCT {{#subobject:e9e363|Regimen=1}}==
−
==SWOG S8736==
 
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 - Control===
+
===Regimen {{#subobject:392c1c|Variant=1}}===
−
*[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 8
 
−
===Arm 2 - Experimental===
 
−
*[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 3, then [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|RT]] x 40 to 55 Gy
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|CHOP x 8
+
|[https://www.nature.com/articles/1705935 Biron et al. 2007 (Pegase 03)]
−
|style="background-color:#fc8d59"|Seems to have inferior OS
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
|-
+
|No further treatment
−
|CHOP x 3, then RT
+
| style="background-color:#1a9850" |Superior DFS
−
|style="background-color:#91cf60"|Seems to have superior OS
 
 
|-
 
|-
 
|}
 
|}
−
===References===
+
====Preceding treatment====
−
# Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. [https://www.nejm.org/doi/full/10.1056/NEJM199807023390104 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9647875 PubMed]
+
*[[Breast_cancer#FEC_3|FEC]] x 4
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]] 6000 mg/m<sup>2</sup>
 +
*[[Thiotepa (Thioplex)]] 800 mg/m<sup>2</sup>
  
−
=[[Follicular lymphoma]]=
 
−
==GALLIUM==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1 - Control===
 
−
*[[Follicular_lymphoma#BR|BR]] x 6 or [[Follicular_lymphoma#R-CHOP|R-CHOP]] x 8 or [[Follicular_lymphoma#R-CVP|R-CVP]] x 8, then [[Follicular_lymphoma#Rituximab_monotherapy.2C_extended_course|Rituximab maintenance]] x 2 y
 
−
===Arm 2 - Experimental===
 
−
*[[Follicular_lymphoma#Bendamustine_.26_Obinutuzumab|Bendamustine & Obinutuzumab]] x 6 or [[Follicular_lymphoma#G-CHOP|G-CHOP]] x 8 or [[Follicular_lymphoma#G-CVP|G-CVP]] x 8, then [[Follicular_lymphoma#Obinutuzumab_monotherapy|Obinutuzumab maintenance]] x 2y
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''mAb'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
![[Levels_of_Evidence#Toxicity|Toxicity]]
 
−
|-
 
−
|Rituximab-chemotherapy
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
| style="background-color:#1a9850" |Superior toxicity
 
−
|-
 
−
|Obinutuzumab-chemotherapy
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
| style="background-color:#d73027" |Inferior toxicity
 
−
|-
 
−
|}
 
 
===References===
 
===References===
−
# Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
+
# '''Pegase 03:''' Biron P, Durand M, Roché H, Delozier T, Battista C, Fargeot P, Spaeth D, Bachelot T, Poiget E, Monnot F, Tanguy ML, Curé H. Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer. Bone Marrow Transplant. 2008 Mar;41(6):555-62. Epub 2007 Nov 26. [https://www.nature.com/articles/1705935 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18037940 PubMed]
  
−
=Gastroesophageal cancer=
+
==CMFP {{#subobject:d1eccf|Regimen=1}}==
−
==ACCORD 07==
 
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 - Control===
+
CMFP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
−
*[[Surgery]] alone
+
===Regimen {{#subobject:6c96a9|Variant=1}}===
−
===Arm 2 - Experimental===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
*[[Esophageal_cancer#Cisplatin_.26_Fluorouracil|Neoadjuvant CF]], then [[surgery]], then [[Esophageal_cancer#Cisplatin_.26_Fluorouracil_3|adjuvant CF]]
+
!style="width: 25%"|Study
−
===Comparative efficacy===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
!style="width: 25%"|Comparator
−
!'''Regimen'''
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Surgery alone
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633086/ Canellos et al. 1974]
−
| style="background-color:#fc8d59" |Seems to have inferior OS
+
| style="background-color:#91cf61" |Non-randomized
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|Perioperative CF
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19821001)50:7%3C1235::AID-CNCR2820500703%3E3.0.CO;2-L Tormey et al. 1982 (ECOG E2173)]
 +
| style="background-color:#1a9851" |Phase III (E-esc)
 +
|1. AV<br> 2. [[Breast_cancer#CMF_2|CMF]]
 
| style="background-color:#91cf60" |Seems to have superior OS
 
| style="background-color:#91cf60" |Seems to have superior OS
 
|-
 
|-
−
|}
+
|[https://link.springer.com/article/10.1007/BF01806026 Segaloff et al. 1985]
−
===References===
+
| style="background-color:#1a9851" |Phase III (C)
−
# Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. Epub 2011 Mar 28. [https://ascopubs.org/doi/full/10.1200/JCO.2010.33.0597 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21444866 PubMed]
+
|[[#CMFVP_2|CMFVP]]
−
 
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
−
==FLOT4-AIO==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1985.3.7.932 Cummings et al. 1985]
−
|}
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
===Arm 1 - Control===
+
|[[#FAC_3|CAF]]
−
*[[Esophageal_cancer#ECF|ECF]] or [[Esophageal_cancer#ECX|ECX]] x 3, then [[surgery]], then [[Esophageal_cancer#ECF_2|ECF]] or [[Esophageal_cancer#ECX_2|ECX]] x 3
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
−
===Arm 2 - Experimental===
 
−
*[[Esophageal_cancer#FLOT|FLOT]] x 4, then [[surgery]], then [[Esophageal_cancer#FLOT_2|FLOT]] x 4
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|ECF/ECX
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F Marschke et al. 1989]
−
|style="background-color:#fc8d59"|Seems to have inferior OS
+
| style="background-color:#1a9851" |Phase III (E-esc)
 +
|[[#CFP_2|CFP]]
 +
| style="background-color:#d9ef8b" |Might have superior ORR
 
|-
 
|-
−
|FLOT
+
|[https://ascopubs.org/doi/10.1200/JCO.1999.17.8.2355 Bishop et al. 1999]
−
|style="background-color:#91cf60"|Seems to have superior OS
+
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 +
====Hormonotherapy====
 +
*[[Prednisone (Sterapred)]]
 +
 
===References===
 
===References===
−
# Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30531-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27776843 PubMed]
+
# Canellos GP, Devita VT, Gold GL, Chabner BA, Schein PS, Young RC. Cyclical combination chemotherapy for advanced breast carcinoma. Br Med J. 1974 Feb 9;1(5901):218-20. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633086/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/4818162 PubMed]
−
## '''Update:''' Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 Apr 10. [Epub ahead of print] [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32557-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30982686 PubMed]
+
# '''ECOG E2173:''' Tormey DC, Gelman R, Band PR, Sears M, Rosenthal SN, DeWys W, Perlia C, Rice MA. Comparison of induction chemotherapies for metastatic breast cancer: an Eastern Cooperative Oncology Group Trial. Cancer. 1982 Oct 1;50(7):1235-44. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19821001)50:7%3C1235::AID-CNCR2820500703%3E3.0.CO;2-L link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7049347 PubMed]
 +
# Segaloff A, Hankey BF, Carter AC, Escher GC, Ansfield FJ, Talley RW. An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone in advanced breast cancer. Breast Cancer Res Treat. 1985;5(3):311-9. [https://link.springer.com/article/10.1007/BF01806026 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3896353 PubMed]
 +
# Cummings FJ, Gelman R, Horton J. Comparison of CAF versus CMFP in metastatic breast cancer: analysis of prognostic factors. J Clin Oncol. 1985 Jul;3(7):932-40. [https://ascopubs.org/doi/abs/10.1200/JCO.1985.3.7.932 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3894587 PubMed]
 +
# Marschke RF Jr, Ingle JN, Schaid DJ, Krook JE, Mailliard JA, Cullinan SA, Pfeifle DM, Votava HJ, Ebbert LP, Windschitl HE. Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer. Cancer. 1989 May 15;63(10):1931-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2649221 PubMed]
 +
# Bishop JF, Dewar J, Toner GC, Smith J, Tattersall MH, Olver IN, Ackland S, Kennedy I, Goldstein D, Gurney H, Walpole E, Levi J, Stephenson J, Canetta R. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2355-64. [https://ascopubs.org/doi/10.1200/JCO.1999.17.8.2355 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10561297 PubMed]
  
−
==MAGIC==
+
==CMFV {{#subobject:e18ffa|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 - Control===
+
CMFV: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>V</u>'''inblastine
−
*[[Esophageal_cancer#Surgery_alone|Surgery]]
+
<br>CVMF: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''inblastine, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
−
===Arm 2 - Experimental===
+
===Regimen {{#subobject:405835|Variant=1}}===
−
*[[Esophageal_cancer#ECF|ECF]] x 3, then [[surgery]], then [[Esophageal_cancer#ECF_2|ECF]] x 3
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
===Comparative efficacy===
+
!style="width: 25%"|Study
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!'''Regimen'''
+
!style="width: 25%"|Comparator
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Surgery alone
+
|[https://www.sciencedirect.com/science/article/pii/S0140673675906765 Edelstyn et al. 1975]
−
|style="background-color:#d73027"|Inferior OS
+
|style="background-color:#1a9851" |Randomized (E-esc)
 +
|[[#CMFV|CMFV]]; 1-day
 +
| style="background-color:#1a9850" |Superior ORR
 
|-
 
|-
−
|Perioperative ECF
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D Bezwoda et al. 1979]
−
|style="background-color:#1a9850"|Superior OS
+
|style="background-color:#1a9851" |Randomized (C)
 +
|[[#CAMF|CAMF]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 +
*[[Vincristine (Oncovin)]]
 
===References===
 
===References===
−
# Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [https://www.nejm.org/doi/full/10.1056/NEJMoa055531 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16822992 PubMed]
+
# Edelstyn GA, Bates TD, Brinkley D, MacRae KD, Spittle MF, Wheeler T. Comparison of 5-day, 1-day, and 2-day cyclical combination chemotherapy in advanced breast cancer. Lancet. 1975 Aug 2;2(7927):209-11. [https://www.sciencedirect.com/science/article/pii/S0140673675906765 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/51964 PubMed]
 +
# Bezwoda WR, de Moor NG, Derman D, Lange M, Saner R, Dando R. Combination chemotherapy of metastatic breast cancer: a randomized trial comparing the use of adriamycin to that of Vinblastine. Cancer. 1979 Aug;44(2):392-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/383254 PubMed]
  
−
==POET==
+
==CMFVP {{#subobject:9920da|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1===
+
CMFVP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
−
*[[Esophageal_cancer#CLF|PLF]] x 15 wk, then [[surgery]]
+
<br>COMFP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
−
===Arm 2===
+
<br>CFPMV: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''incristine
−
*[[Esophageal_cancer#CLF|PLF]] x 12 wk, then [[Esophageal_cancer#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]], then [[surgery]]
+
===Regimen {{#subobject:e01cbf|Variant=1}}===
−
===Comparative efficacy===
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
!style="width: 25%"|Study
−
!'''Regimen'''
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Neoadjuvant chemotherapy only
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197708)40:2%3C625::AID-CNCR2820400206%3E3.0.CO;2-M Smalley et al. 1977]
−
|style="background-color:#fee08b"|Might have inferior OS
+
|style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer#FAC_3|CAF]]
 +
| style="background-color:#fee08b" |Might have inferior OS (*)
 
|-
 
|-
−
|Neoadjuvant chemotherapy and chemoradiotherapy
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 Muss et al. 1978]
−
|style="background-color:#d9ef8b"|Might have superior OS
+
|style="background-color:#1a9851" |Phase III (C)
 +
|[[#CAFVP|CAFVP]]
 +
| style="background-color:#fee08b" |Might have inferior OS
 
|-
 
|-
−
|}
+
|[https://link.springer.com/article/10.1007/BF01806026 Segaloff et al. 1985]
−
===References===
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
# Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. [https://ascopubs.org/doi/full/10.1200/JCO.2008.17.0506 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19139439 PubMed]
+
|[[#CMFP_2|CMFP]]
−
 
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
−
==PRODIGE5/ACCORD17==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O Rosner et al. 1987]
−
|}
+
| style="background-color:#1a9851" |Phase III (E-esc)
−
===Arm 1 - Control===
+
|1. [[Breast_cancer#AC_3|CA]]<br> 2. [[#CFP_2|CFP]]
−
*[[Esophageal_cancer#Cisplatin.2C_Fluorouracil.2C_RT_2|Definitive CF & RT]], then [[Esophageal_cancer#Cisplatin_.26_Fluorouracil_2|CF]] x 2
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
−
===Arm 2 - Experimental===
 
−
*[[Esophageal_cancer#FOLFOX4_.26_RT|Definitive FOLFOX4 & RT]], then [[Esophageal_cancer#FOLFOX4|FOLFOX4]] x 3
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|CF-based
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|FOLFOX4-based
 
−
| style="background-color:#ffffbf" |Seems not superior
 
 
|-
 
|-
 
|}
 
|}
 +
''Note: reported efficacy for Smalley et al. 1977 is based on the 1983 update.''
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Fluorouracil (5-FU)]]
 +
*[[Vincristine (Oncovin)]]
 +
====Hormonotherapy====
 +
*[[Prednisone (Sterapred)]]
 
===References===
 
===References===
−
# Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24556041 PubMed]
+
# Smalley RV, Carpenter J, Bartolucci A, Vogel C, Krauss S. A comparison of cyclophosphamide, adriamycin, 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone (CMFVP) in patients with metastatic breast cancer: a Southeastern Cancer Study Group project. Cancer. 1977 Aug;40(2):625-32. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197708)40:2%3C625::AID-CNCR2820400206%3E3.0.CO;2-M link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/329975 PubMed]
 +
## '''Update:''' Smalley RV, Lefante J, Bartolucci A, Carpenter J, Vogel C, Krauss S. A comparison of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) in patients with advanced breast cancer. Breast Cancer Res Treat. 1983;3(2):209-20. [https://link.springer.com/article/10.1007/BF01803563 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6688538 PubMed]
 +
# Muss HB, White DR, Richards F 2nd, Cooper MR, Stuart JJ, Jackson DV, Rhyne L, Spurr CL. Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial. Cancer. 1978 Nov;42(5):2141-8. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/363253 PubMed]
 +
# Segaloff A, Hankey BF, Carter AC, Escher GC, Ansfield FJ, Talley RW. An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone in advanced breast cancer. Breast Cancer Res Treat. 1985;5(3):311-9. [https://link.springer.com/article/10.1007/BF01806026 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3896353 PubMed]
 +
# Rosner D, Nemoto T, Lane WW. A randomized study of intensive versus moderate chemotherapy programs in metastatic breast cancer. Cancer. 1987 Mar 1;59(5):874-83. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3815266 PubMed]
  
−
=[[Glioblastoma]]=
+
==DES monotherapy {{#subobject:0a1860|Regimen=1}}==
−
==AVAglio==
 
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, control===
+
===Regimen {{#subobject:128a40|Variant=1}}===
−
*[[Surgery]], then [[Glioblastoma#Temozolomide_.26_RT|adjuvant temozolomide & RT]], then [[Glioblastoma#Temozolomide_monotherapy_2|temozolomide maintenance]]
 
−
===Arm 2, experimental===
 
−
*[[Surgery]], then adjuvant temozolomide, bevacizumab, RT, then temozolomide & bevacizumab maintenance, then bevacizumab maintenance
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Temozolomide alone
+
|[https://www.ncbi.nlm.nih.gov/pubmed/14285946 Kennedy 1965]
−
|style="background-color:#d73027"|Inferior PFS
+
| style="background-color:#1a9851" |Randomized (E-switch-ic)
 +
|Testosterone
 +
| style="background-color:#d3d3d3" |Not available
 
|-
 
|-
−
|Bevacizumab-containing arm
+
|[https://jamanetwork.com/journals/jama/article-abstract/353009 Carter et al. 1977]
−
|style="background-color:#1a9850"|Superior PFS
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 +
|[[#DES_monotherapy|DES]]; other dosings
 +
| style="background-color:#d3d3d3" |See paper
 
|-
 
|-
−
|}
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198101013040104 Ingle et al. 1981]
−
===References===
+
| style="background-color:#1a9851" |Phase III (C)
−
# Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):709-22. [https://www.nejm.org/doi/full/10.1056/NEJMoa1308345 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24552318 PubMed]
+
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
−
 
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
−
==EORTC 22981/26981; NCIC CTG CE.3==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19810201)47:3%3C452::AID-CNCR2820470305%3E3.0.CO;2-Y Kiang et al. 1981]
−
|}
+
| style="background-color:#1a9851" |Phase III (C)
−
===Arm 1, control===
+
|Cyclophosphamide, 5-FU, DES
−
*[[Surgery]], then [[Glioblastoma#Radiation_therapy|adjuvant radiotherapy]]
+
| style="background-color:#fc8d59" |Seems to have inferior OS (*)
−
===Arm 2, experimental===
 
−
*[[Surgery]], then [[Glioblastoma#Temozolomide_.26_RT|adjuvant Temozolomide & RT]], then [[Glioblastoma#Temozolomide_monotherapy_2|Temozolomide]] maintenance
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Radiotherapy alone
 
−
|style="background-color:#d73027"|Inferior OS
 
−
|-
 
−
|Temozolomide-containing arm
 
−
|style="background-color:#1a9850"|Superior OS
 
 
|-
 
|-
 
|}
 
|}
 +
''No longer used, but of historical interest. Reported efficacy for Kiang et al. 1981 is based on the 1985 update.''
 +
====Hormonotherapy====
 +
*[[Diethylstilbestrol (DES)]]
 +
 
===References===
 
===References===
−
# Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. [https://www.nejm.org/doi/full/10.1056/NEJMoa043330 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15758009 PubMed]
+
# Kennedy BJ. Diethylstilbestrol versus testosterone propionate therapy in advanced breast cancer. Surg Gynecol Obstet. 1965 Jun;120:1246-50. [https://www.ncbi.nlm.nih.gov/pubmed/14285946 PubMed]
 +
# Carter AC, Sedransk N, Kelley RM, Ansfield FJ, Ravdin RG, Talley RW, Potter NR. Diethylstilbestrol: recommended dosages for different categories of breast cancer patients: report of the Cooperative Breast Cancer Group. JAMA. 1977 May 9;237(19):2079-8. [https://jamanetwork.com/journals/jama/article-abstract/353009 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/576887 PubMed]
 +
# Ingle JN, Ahmann DL, Green SJ, Edmonson JH, Bisel HF, Kvols LK, Nichols WC, Creagan ET, Hahn RG, Rubin J, Frytak S. Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N Engl J Med. 1981 Jan 1;304(1):16-21. [https://www.nejm.org/doi/full/10.1056/NEJM198101013040104 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7001242 PubMed]
 +
# Kiang DT, Frenning DH, Gay J, Goldman AI, Kennedy BJ. Combination therapy of hormone and cytotoxic agents in advanced breast cancer. Cancer. 1981 Feb 1;47(3):452-6. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19810201)47:3%3C452::AID-CNCR2820470305%3E3.0.CO;2-Y link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7013960 PubMed]
 +
## '''Update:''' Kiang DT, Gay J, Goldman A, Kennedy BJ. A randomized trial of chemotherapy and hormonal therapy in advanced breast cancer. N Engl J Med. 1985 Nov 14;313(20):1241-6. [https://www.nejm.org/doi/full/10.1056/NEJM198511143132001 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3903501 PubMed]
  
−
==HERBY==
+
==CTCb, then auto HSCT {{#subobject:02f569|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, control===
+
CTCb: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''hiotepa, '''<u>C</u>'''ar'''<u>b</u>'''oplatin
−
*[[Surgery]], then [[Glioblastoma#Temozolomide_.26_RT|adjuvant temozolomide & RT]], then [[Glioblastoma#Temozolomide_monotherapy_2|temozolomide maintenance]]
+
 
−
===Arm 2, experimental===
+
===Regimen {{#subobject:3dea9c|Variant=1}}===
−
*[[Surgery]], then adjuvant temozolomide, bevacizumab, RT, then temozolomide & bevacizumab maintenance
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
|-
+
!style="width: 25%"|Comparator
−
|Temozolomide alone
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
| style="background-color:#ffffbf" |Seems not superior
 
 
|-
 
|-
−
|Bevacizumab-containing arm
+
|[https://www.nejm.org/doi/full/10.1056/NEJM200004133421501 Stadtmauer et al. 2000]
−
| style="background-color:#ffffbf" |Seems not superior
+
| style="background-color:#1a9851" |Phase III (E-esc)
 +
|[[Breast_cancer#CMF_2|CMF]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
 
|}
 
|}
 +
''No longer used, but of historical interest.''
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Thiotepa (Thioplex)]]
 +
*[[Carboplatin (Paraplatin)]]
 +
 
===References===
 
===References===
−
# Grill J, Massimino M, Bouffet E, Azizi AA, McCowage G, Cañete A, Saran F, Le Deley MC, Varlet P, Morgan PS, Jaspan T, Jones C, Giangaspero F, Smith H, Garcia J, Elze MC, Rousseau RF, Abrey L, Hargrave D, Vassal G. Phase II, open-label, randomized, multicenter trial (HERBY) of bevacizumab in pediatric patients with newly diagnosed high-grade glioma. J Clin Oncol. 2018 Apr 1;36(10):951-958. Epub 2018 Feb 7. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.0611 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29412784 PubMed]
+
# Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK, Sickles C, Glick JH; Philadelphia Bone Marrow Transplant Group. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med. 2000 Apr 13;342(15):1069-76. [https://www.nejm.org/doi/full/10.1056/NEJM200004133421501 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10760307 PubMed]
  
−
==RTOG 0825==
+
==Estradiol monotherapy {{#subobject:edd4bd|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, control===
+
===Variant #1, 6 mg/day {{#subobject:8e8202|Variant=1}}===
−
*[[Surgery]], then [[Glioblastoma#Temozolomide_.26_RT|adjuvant Temozolomide & RT]], then [[Glioblastoma#Temozolomide_monotherapy_2|Temozolomide]] maintenance
 
−
===Arm 2, experimental===
 
−
*[[Surgery]], then adjuvant Temozolomide, Bevacizumab, RT, then Temozolomide & Bevacizumab maintenance
 
−
===Comparative efficacy===
 
−
''Note: although the control regimen had inferior PFS, the effect size did not reach the prespecified improvement target.''
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Temozolomide alone
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460383/ Ellis et al. 2009]
−
|style="background-color:#d73027"|Inferior PFS
+
| style="background-color:#1a9851" |Randomized Phase II (E-de-esc)
−
|-
+
|[[#Estradiol_monotherapy|Estradiol]]; 30 mg/day
−
|Bevacizumab-containing arm
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of CBR
−
|style="background-color:#1a9850"|Superior PFS
 
 
|-
 
|-
 
|}
 
|}
−
===References===
+
====Hormonotherapy====
−
# Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. [https://www.nejm.org/doi/full/10.1056/NEJMoa1308573 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201043/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24552317 PubMed]
+
*[[Estradiol]] 6 mg PO once per day
  
−
=[[Head and neck cancer]]=
+
'''Continued indefinitely'''
−
==EORTC 24954==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1, control===
 
−
*[[Head_and_neck_cancer#Cisplatin_.26_Fluorouracil|CF]] x 4, then [[Head_and_neck_cancer#Radiation_therapy|RT]]
 
−
===Arm 2, experimental===
 
−
*[[Head_and_neck_cancer#Cisplatin.2C_Fluorouracil.2C_RT|CF/RT]]
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Sequential RT
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|Alternating RT
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|}
 
−
===References===
 
−
# Lefebvre JL, Rolland F, Tesselaar M, Bardet E, Leemans CR, Geoffrois L, Hupperets P, Barzan L, de Raucourt D, Chevalier D, Licitra L, Lunghi F, Stupp R, Lacombe D, Bogaerts J, Horiot JC, Bernier J, Vermorken JB; EORTC Head and Neck Cancer Cooperative Group; EORTC Radiation Oncology Group. Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. J Natl Cancer Inst. 2009 Feb 4;101(3):142-52. Epub 2009 Jan 27. [https://academic.oup.com/jnci/article/101/3/142/947754 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724854/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19176454 PubMed]
 
  
−
==RTOG 91-11==
+
===Variant #2, 30 mg/day {{#subobject:8fahc02|Variant=1}}===
−
===Arm 1, induction chemotherapy, then radiotherapy (Control)===
 
−
*[[Head_and_neck_cancer#Cisplatin_.26_Fluorouracil|PF]] x 3, then [[Head_and_neck_cancer#Radiation_therapy|RT]]
 
−
===Arm 2, concurrent chemoradiotherapy (Experimental)===
 
−
*[[Head_and_neck_cancer#Cisplatin_.26_RT|Cisplatin & RT]]
 
−
===Arm 3, radiotherapy (Experimental)===
 
−
*[[Head_and_neck_cancer#Radiation_therapy|RT]]
 
−
===Comparative efficacy===
 
−
''Efficacy is based on the 2012 update.''
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen vs.'''
+
!style="width: 25%"|Study
−
!'''Arm 1'''
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!'''Arm 2'''
+
!style="width: 25%"|Comparator
−
!'''Arm 3'''
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
|-
 
−
|Arm 1 vs.
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d73027" |Inferior LFS
 
−
| style="background-color:#91cf60" |Seems to have superior LFS
 
 
|-
 
|-
−
|Arm 2 vs.
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460383/ Ellis et al. 2009]
−
| style="background-color:#1a9850" |Superior LFS
+
| style="background-color:#1a9851" |Randomized Phase II (C)
−
| style="background-color:#d3d3d3" |
+
|[[#Estradiol_monotherapy|Estradiol]]; 6 mg/day
−
| style="background-color:#91cf60" |Seems to have superior LFS
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of CBR
−
|-
 
−
|Arm 3 vs.
 
−
| style="background-color:#fc8d59" |Seems to have inferior LFS
 
−
| style="background-color:#fc8d59" |Seems to have inferior LFS
 
−
| style="background-color:#d3d3d3" |
 
 
|-
 
|-
 
|}
 
|}
−
===References===
+
====Hormonotherapy====
−
# Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. [https://www.nejm.org/doi/full/10.1056/NEJMoa031317 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14645636 PubMed]
+
*[[Estradiol]] 30 mg PO once per day
−
## '''Update:''' Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. [http://jco.ascopubs.org/content/31/7/845.long link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577950/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23182993 PubMed]
 
  
−
=[[Hodgkin lymphoma]]=
+
'''Continued indefinitely'''
−
==EORTC 20012==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1===
 
−
*[[Hodgkin_lymphoma#eBEACOPP_2|eBEACOPP]] x 4, then [[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]] x 4
 
−
===Arm 2===
 
−
*[[Hodgkin_lymphoma#ABVD_3|ABVD]] x 8
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|BEACOPP<sub>4+4</sub>
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
 
−
|-
 
−
|ABVD x 8
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
  
 
===References===
 
===References===
−
# Carde P, Karrasch M, Fortpied C, Brice P, Khaled H, Casasnovas O, Caillot D, Gaillard I, Bologna S, Ferme C, Lugtenburg PJ, Morschhauser F, Aurer I, Coiffier B, Meyer R, Seftel M, Wolf M, Glimelius B, Sureda A, Mounier N. Eight cycles of ABVD versus four cycles of BEACOPP<sub>escalated</sub> plus four cycles of BEACOPP<sub>baseline</sub> in stage III to IV, International Prognostic Score ≥ 3, high-risk Hodgkin lymphoma: First results of the phase III EORTC 20012 Intergroup trial. J Clin Oncol. 2016 Jun 10;34(17):2028-36. Epub 2016 Apr 25. [http://jco.ascopubs.org/content/34/17/2028.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27114593 PubMed]
+
# Ellis MJ, Gao F, Dehdashti F, Jeffe DB, Marcom PK, Carey LA, Dickler MN, Silverman P, Fleming GF, Kommareddy A, Jamalabadi-Majidi S, Crowder R, Siegel BA. Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study. JAMA. 2009 Aug 19;302(7):774-80. [https://jamanetwork.com/journals/jama/fullarticle/184425 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460383/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19690310 PubMed]
  
−
==EORTC-GELA H8-F==
+
==Fluoxymesterone monotherapy {{#subobject:835187|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1===
+
===Regimen {{#subobject:1914f4|Variant=1}}===
−
*[[Hodgkin_lymphoma#MOPP-ABV|MOPP-ABV]] x 3, then [[Hodgkin_lymphoma#Radiotherapy_2|IFRT]]
+
{| class="wikitable" style="width: 50%; text-align:center;"  
−
===Arm 2===
+
!style="width: 25%"|Study
−
*[[Hodgkin_lymphoma#Radiotherapy|STNI]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|MOPP-ABV x 3, then IFRT
+
|[https://www.nejm.org/doi/full/10.1056/NEJM195810022591404 Kennedy 1958]
−
|style="background-color:#1a9850"|Superior OS
+
| style="background-color:#91cf61" |Non-randomized
−
|-
 
−
|STNI
 
−
|style="background-color:#d73027"|Inferior OS
 
 
|-
 
|-
 
|}
 
|}
 +
====Hormonotherapy====
 +
*[[Fluoxymesterone (Halotestin)]]
 
===References===
 
===References===
−
# Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. [https://www.nejm.org/doi/full/10.1056/NEJMoa064601 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/17989384 PubMed]
+
# Kennedy BJ. Fluoxymesterone therapy in advanced breast cancer. N Engl J Med. 1958 Oct 2;259(14):673-5. [https://www.nejm.org/doi/full/10.1056/NEJM195810022591404 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/13590423 PubMed]
  
−
==EORTC-GELA H8-U==
+
==Formestane monotherapy {{#subobject:6c7bb9|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1===
+
===Regimen {{#subobject:8b5e67|Variant=1}}===
−
*[[Hodgkin_lymphoma#MOPP-ABV_2|MOPP-ABV]] x 4, then [[Hodgkin_lymphoma#Radiotherapy_2|IFRT]]
 
−
===Arm 2===
 
−
*[[Hodgkin_lymphoma#MOPP-ABV_2|MOPP-ABV]] x 4, then [[Hodgkin_lymphoma#Radiotherapy_2|STNI]]
 
−
===Arm 3===
 
−
*[[Hodgkin_lymphoma#MOPP-ABV_2|MOPP-ABV]] x 6, then [[Hodgkin_lymphoma#Radiotherapy_2|IFRT]]
 
−
===Comparative efficacy===
 
−
''Note: the paper describes this as an equivalence study, although the primary endpoint of EFS had p=0.80.''
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|MOPP-ABV x 4, then IFRT
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)92795-8/fulltext Coombes et al. 1984]
−
|style="background-color:#ffffbf"|Inconclusive whether equivalent
+
| style="background-color:#ffffbe" |Pilot
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|MOPP-ABV x 4, then STNI
+
|[https://www.ejcancer.com/article/S0959-8049(97)00105-6/pdf Thürlimann et al. 1997 (SAKK 20/90)]
−
|style="background-color:#ffffbf"|Inconclusive whether equivalent
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
−
|-
+
|[[#Megestrol_monotherapy|Megestrol]]
−
|MOPP-ABV x 6, then IFRT
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
−
|style="background-color:#ffffbf"|Inconclusive whether equivalent
 
 
|-
 
|-
 
|}
 
|}
 +
====Hormonotherapy====
 +
*[[Formestane (Lentaron)]]
 
===References===
 
===References===
−
# Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. [https://www.nejm.org/doi/full/10.1056/NEJMoa064601 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/17989384 PubMed]
+
# Coombes RC, Goss P, Dowsett M, Gazet JC, Brodie A. 4-Hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. Lancet. 1984 Dec 1;2(8414):1237-9. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)92795-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6150277 PubMed]
 +
# '''SAKK 20/90:''' Thürlimann B, Castiglione M, Hsu-Schmitz SF, Cavalli F, Bonnefoi H, Fey MF, Morant R, Löhnert T, Goldhirsch A; Swiss Group for Clinical Cancer Research (SAKK). Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Eur J Cancer. 1997 Jun;33(7):1017-24. [https://www.ejcancer.com/article/S0959-8049(97)00105-6/pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9376181 PubMed]
  
−
==EORTC/LYSA/FIL H10==
+
==Medroxyprogesterone monotherapy {{#subobject:6c7bb9|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
''Note: randomization in this trial occurred before treatment, but took effect after 2 cycles of ABVD, and only if interim PET-CT was negative.''
+
===Variant #1, 500 mg/day {{#subobject:8b5e67|Variant=1}}===
−
===Arm 1===
 
−
*Favorable: [[Hodgkin_lymphoma#ABVD|ABVD]] x 4
 
−
*Unfavorable: [[Hodgkin_lymphoma#ABVD|ABVD]] x 6
 
−
===Arm 2===
 
−
*Favorable: [[Hodgkin_lymphoma#ABVD|ABVD]] x 3, then [[Hodgkin_lymphoma#Radiotherapy_2|INRT]]
 
−
*Unfavorable: [[Hodgkin_lymphoma#ABVD|ABVD]] x 4, then [[Hodgkin_lymphoma#Radiotherapy_2|INRT]]
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|ABVD x 4
+
|[https://journals.sagepub.com/doi/abs/10.1177/030089167806400204 Cuna et al. 1978]
−
|style="background-color:#ffffbf"|Inconclusive whether non-inferior
+
|style="background-color:#1a9851"|Phase III (E-de-esc)
−
|-
+
|[[#Medroxyprogesterone_monotherapy|MPA]]; 1000 mg/day
−
|ABVD x 3, then INRT
+
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
−
|style="background-color:#ffffbf"|Inconclusive whether non-inferior
 
−
|-
 
−
|}
 
−
===References===
 
−
# Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. [http://jco.ascopubs.org/content/32/12/1188.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24637998 PubMed]
 
−
## '''Update:''' André MPE, Girinsky T, Federico M, Reman O, Fortpied C, Gotti M, Casasnovas O, Brice P, van der Maazen R, Re A, Edeline V, Fermé C, van Imhoff G, Merli F, Bouabdallah R, Sebban C, Specht L, Stamatoullas A, Delarue R, Fiaccadori V, Bellei M, Raveloarivahy T, Versari A, Hutchings M, Meignan M, Raemaekers J. Early positron emission tomography response-adapted treatment in stage I and II Hodgkin lymphoma: final results of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2017 Jun 1;35(16):1786-1794. Epub 2017 Mar 14. [https://ascopubs.org/doi/full/10.1200/JCO.2016.68.6394 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28291393 PubMed]
 
−
 
 
−
==GHSG HD11==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://www.ejcancer.com/article/0014-2964(79)90097-5/abstract Pannuti et al. 1979]
−
|}
+
|style="background-color:#1a9851"|Phase III (C)
−
''Note: the primary endpoints of this trial, which were to determine the superiority of BEACOPP vs. ABVD and noninferiority of 20 Gy vs. 30 Gy of IFRT, were not reported in the manuscript.''
+
|[[#Medroxyprogesterone_monotherapy|MPA]]; 1500 mg/day
−
===Arm 1===
+
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
−
*[[Hodgkin_lymphoma#ABVD_2|ABVD]] x 4, then [[Hodgkin_lymphoma#Radiotherapy_2|IFRT]] x 30 Gy
 
−
===Arm 2===
 
−
*[[Hodgkin_lymphoma#ABVD_2|ABVD]] x 4, then [[Hodgkin_lymphoma#Radiotherapy_2|IFRT]] x 20 Gy
 
−
===Arm 3===
 
−
*[[Hodgkin_lymphoma#BEACOPP|BEACOPP]] x 4, then [[Hodgkin_lymphoma#Radiotherapy_2|IFRT]] x 30 Gy
 
−
===Arm 4===
 
−
*[[Hodgkin_lymphoma#BEACOPP|BEACOPP]] x 4, then [[Hodgkin_lymphoma#Radiotherapy_2|IFRT]] x 20 Gy
 
−
===Comparative efficacy===
 
−
*Designed using a 2 x 2 factorial design
 
−
====Comparison 1====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
|'''Chemotherapy'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|ABVD
+
|[https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 Canney et al. 1988]
−
|style="background-color:#d3d3d3"|Not reported
+
|style="background-color:#1a9851"|Phase III (C)
 +
|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
|-
 
|-
−
|BEACOPP
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.9.3141 Byrne et al. 1997 (ANZ8613)]
−
|style="background-color:#d3d3d3"|Not reported
+
|style="background-color:#1a9851"|Phase III (C)
 +
|MPA & Tamoxifen
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of TTP
 
|-
 
|-
 
|}
 
|}
−
====Comparison 2====
+
''Note: Canney et al. 1988 does not have dosing information in the abstract.''
 +
====Hormonotherapy====
 +
*[[Medroxyprogesterone (MPA)]] 500 mg PO once per day
 +
 
 +
'''Continued indefinitely'''
 +
 
 +
===Variant #2, 900 mg/day {{#subobject:88ge67|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
|'''Radiotherapy'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|IFRT x 20 Gy
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19860701)58:1%3C7::AID-CNCR2820580103%3E3.0.CO;2-%23 van Veelen et al. 1986]
−
|style="background-color:#d3d3d3"|Not reported
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
−
|-
+
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
−
|IFRT x 30 Gy
+
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
−
|style="background-color:#d3d3d3"|Not reported
 
 
|-
 
|-
 
|}
 
|}
−
===References===
+
====Hormonotherapy====
−
# Eich HT, Diehl V, Görgen H, Pabst T, Markova J, Debus J, Ho A, Dörken B, Rank A, Grosu AL, Wiegel T, Karstens JH, Greil R, Willich N, Schmidberger H, Döhner H, Borchmann P, Müller-Hermelink HK, Müller RP, Engert A. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010 Sep 20;28(27):4199-206. Epub 2010 Aug 16. [http://jco.ascopubs.org/content/28/27/4199.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20713848 PubMed]
+
*[[Medroxyprogesterone (MPA)]] 300 mg PO three times per day
 +
 
 +
'''Continued indefinitely'''
  
−
==GHSG HD12==
+
===Variant #3, 1000 mg/day (high-dose) {{#subobject:62af61|Variant=1}}===
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1===
 
−
*[[Hodgkin_lymphoma#eBEACOPP_2|eBEACOPP]] x 8, then [[Hodgkin_lymphoma#Radiotherapy_2|ISRT]] x 30 Gy for patients with initial bulky disease or residual disease
 
−
===Arm 2===
 
−
*[[Hodgkin_lymphoma#eBEACOPP_2|eBEACOPP]] x 8, then [[Hodgkin_lymphoma#Observation|no further treatment]] for patients with initial bulky disease or residual disease
 
−
===Arm 3===
 
−
*[[Hodgkin_lymphoma#eBEACOPP_2|eBEACOPP]] x 4, then [[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]] x 4, then [[Hodgkin_lymphoma#Radiotherapy_2|ISRT]] x 30 Gy for patients with initial bulky disease or residual disease
 
−
===Arm 4===
 
−
*[[Hodgkin_lymphoma#eBEACOPP_2|eBEACOPP]] x 4, then [[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]] x 4, then [[Hodgkin_lymphoma#Observation|no further treatment]] for patients with initial bulky disease or residual disease
 
−
===Comparative efficacy===
 
−
*Designed using a 2 x 2 factorial design
 
−
====Comparison 1====
 
−
''Reported efficacy is based on the 2018 update.''
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
|'''Chemotherapy'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
|-
+
!style="width: 25%"|Comparator
−
|eBEACOPP x 8
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
|style="background-color:#eeee01"|Non-inferior OS (*)
 
 
|-
 
|-
−
|eBEACOPP x 4, then BEACOPP x 4
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1984.2.5.414 Cavalli et al. 1984]
−
|style="background-color:#eeee01"|Non-inferior OS (*)
+
|style="background-color:#1a9851"|Phase III (E-esc)
 +
|[[#Medroxyprogesterone_monotherapy|MPA]]; low-dose
 +
| style="background-color:#1a9850" |Superior ORR
 
|-
 
|-
−
|}
+
|[https://link.springer.com/article/10.1007/BF01961246 Garcia-Giralt et al. 1992]
−
====Comparison 2====
+
| style="background-color:#1a9851" |Phase III (C)
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]
−
|'''Radiotherapy'''
+
| style="background-color:#fc8d59" |Seems to have inferior TTP
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|ISRT x 30 Gy
+
|[https://academic.oup.com/annonc/article-abstract/4/9/735/170824 Castiglione-Gertsch et al. 1993]
−
|style="background-color:#d9ef8b"|Might have superior 5-year FFTF
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 +
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
 +
| style="background-color:#d9ef8b" |Might have superior TTP
 
|-
 
|-
−
|No radiotherapy
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1994.12.8.1630 Muss et al. 1994]
−
|style="background-color:#fee08b"|Might have inferior 5-year FFTF
+
|style="background-color:#1a9851"|Phase III (E-switch-ic)
 +
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 
|-
 
|-
 
|}
 
|}
 +
====Hormonotherapy====
 +
*[[Medroxyprogesterone (MPA)]] 1000 mg PO or IM once per day
 +
**Garcia-Giralt et al. 1992 gave as 500 mg PO twice per day
 +
 +
'''Continued indefinitely'''
 +
 
===References===
 
===References===
−
# Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. [http://jco.ascopubs.org/content/29/32/4234.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21990399 PubMed]
+
# Cuna GR, Calciati A, Strada MR, Bumma C, Campio L. High dose medroxyprogesterone acetate (MPA) treatment in metastatic carcinoma of the breast: a dose-response evaluation. Tumori. 1978 Apr 30;64(2):143-9. [https://journals.sagepub.com/doi/abs/10.1177/030089167806400204 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/354147 PubMed]
−
## '''Update:''' von Tresckow B, Kreissl S, Dipl-Math HG, Bröckelmann PJ, Pabst T, Fridrik M, Rummel M, Jung W, Thiemer J, Sasse S, Bürkle C, Baues C, Diehl V, Engert A, Borchmann P; German Hodgkin Study Group. Intensive treatment strategies in advanced-stage Hodgkin's lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trials. Lancet Haematol. 2018 Oct 01;5(10):e462-73. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30140-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30290903 PubMed]
+
# Pannuti F, Martoni A, Di Marco AR, Piana E, Saccani F, Becchi G, Mattioli G, Barbanti F, Marra GA, Persiani W, Cacciari L, Spagnolo F, Palenzona D, Rocchetta G. Prospective, randomized clinical trial of two different high dosages of medroxyprogesterone acetate (MAP) in the treatment of metastatic breast cancer. Eur J Cancer. 1979 Apr;15(4):593-601. [https://www.ejcancer.com/article/0014-2964(79)90097-5/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/86447 PubMed]
 +
# Cavalli F, Goldhirsch A, Jungi F, Martz G, Mermillod B, Alberto P. Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer. J Clin Oncol. 1984 May;2(5):414-9. [https://ascopubs.org/doi/abs/10.1200/JCO.1984.2.5.414 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6233398 PubMed]
 +
# van Veelen H, Willemse PH, Tjabbes T, Schweitzer MJ, Sleijfer DT. Oral high-dose medroxyprogesterone acetate versus tamoxifen: a randomized crossover trial in postmenopausal patients with advanced breast cancer. Cancer. 1986 Jul 1;58(1):7-13. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19860701)58:1%3C7::AID-CNCR2820580103%3E3.0.CO;2-%23 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2939943 PubMed]
 +
# Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, Spooner D. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. J Natl Cancer Inst. 1988 Sep 21;80(14):1147-51. [https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2970555 PubMed]
 +
# Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P, Fumoleau P, Gorins A, Guerin D, Guerin R, Maillart P, Mauriac L, May-Levin F, Metz R, Namer M, Olivier JP, Pommatau E, Pouillart P, Pujade-Lauraine E, Rouesse J, Serrou B, Vitse M, Zylberait D. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Res Treat. 1992;24(2):139-45. [https://link.springer.com/article/10.1007/BF01961246 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8443401 PubMed]
 +
# Castiglione-Gertsch M, Pampallona S, Varini M, Cavalli F, Brunner K, Senn HJ, Goldhirsch A, Metzger U. Primary endocrine therapy for advanced breast cancer: to start with tamoxifen or with medroxyprogesterone acetate?. Ann Oncol. 1993 Nov;4(9):735-40. [https://academic.oup.com/annonc/article-abstract/4/9/735/170824 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8280653 PubMed]
 +
# Muss HB, Case LD, Atkins JN, Bearden JD 3rd, Cooper MR, Cruz JM, Jackson DV Jr, O'Rourke MA, Pavy MD, Powell BL, Richards F, SPurr CL, Eagle K, White DR. Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study. J Clin Oncol. 1994 Aug;12(8):1630-8. [https://ascopubs.org/doi/abs/10.1200/JCO.1994.12.8.1630 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8040675 PubMed]
 +
# '''ANZ8613:''' Byrne MJ, Gebski V, Forbes J, Tattersall MH, Simes RJ, Coates AS, Dewar J, Lunn M, Flower C, Gill PG, Stewart J; Australian-New Zealand Breast Cancer Trials Group. Medroxyprogesterone acetate addition or substitution for tamoxifen in advanced tamoxifen-resistant breast cancer: a phase III randomized trial. J Clin Oncol. 1997 Sep;15(9):3141-8. [https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.9.3141 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9294477 PubMed]
  
−
==GHSG HD14==
+
==Megestrol monotherapy {{#subobject:a806f8|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1===
+
===Regimen {{#subobject:27fd99|Variant=1}}===
−
*[[Hodgkin_lymphoma#ABVD_2|ABVD]] x 4, then [[Hodgkin_lymphoma#Radiotherapy_2|IFRT]] x 30 Gy
 
−
===Arm 2===
 
−
*[[Hodgkin_lymphoma#eBEACOPP|eBEACOPP]] x 2, then [[Hodgkin_lymphoma#ABVD_2|ABVD]] x 2, then [[Hodgkin_lymphoma#Radiotherapy_2|IFRT]] x 30 Gy
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
|'''Chemotherapy'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|ABVD x 4
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1988.6.7.1098 Muss et al. 1988]
−
|style="background-color:#d73027"|Inferior FFTF
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 +
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
|-
 
|-
−
|eBEACOPP x 2, then ABVD x 2
+
|[https://link.springer.com/article/10.1007/BF01810736 Lundgren et al. 1989]
−
|style="background-color:#1a9850"|Superior FFTF
+
| style="background-color:#1a9851" |Phase III (C)
 +
|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
|-
 
|-
−
|}
+
|[https://ascopubs.org/doi/10.1200/jco.1990.8.11.1797 Muss et al. 1990]
−
===References===
+
| style="background-color:#1a9851" |Phase III (C)
−
<!-- Presented in part at the 52nd Annual Meeting of the American Society of Hematology, December 4-7, 2010, Orlando, FL. -->
+
|[[#Megestrol_monotherapy|Megestrol]]; higher-dose
−
# von Tresckow B, Plütschow A, Fuchs M, Klimm B, Markova J, Lohri A, Kral Z, Greil R, Topp MS, Meissner J, Zijlstra JM, Soekler M, Stein H, Eich HT, Mueller RP, Diehl V, Borchmann P, Engert A. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012 Mar 20;30(9):907-13. Epub 2012 Jan 23. [http://jco.ascopubs.org/content/30/9/907.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22271480 PubMed]
+
| style="background-color:#fc8d59" |Seems to have inferior OS
−
 
 
−
==GSM-HD==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://academic.oup.com/annonc/article-abstract/4/9/741/170864 Gill et al. 1993]
−
|}
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
−
===Arm 1===
+
|1. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]<br> 2. Megestrol & Tamoxifen
−
*[[Hodgkin_lymphoma#eBEACOPP_2|eBEACOPP]] x 4, then [[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]] x 4
+
| style="background-color:#ffffbf" |Seems not superior
−
===Arm 2===
 
−
*[[Hodgkin_lymphoma#ABVD_3|ABVD]] x 8
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|BEACOPP<sub>4+4</sub>
+
|[https://www.ejcancer.com/article/0959-8049(95)00014-3/pdf Jonat et al. 1996]
−
|style="background-color:#91cf60"|Seems to have superior FFFP
+
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer,_ER-positive#Anastrozole_monotherapy_4|Anastrozole]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS (*)
 
|-
 
|-
−
|ABVD x 8
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1097-0142(19960615)77:12%3C2503::AID-CNCR13%3E3.0.CO;2-W Buzdar et al. 1996 (Protocol 03)]
−
|style="background-color:#fc8d59"|Seems to have inferior FFFP
+
| style="background-color:#1a9851" |Phase III (C)
 +
|Fadrozole
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
|-
 
|-
−
|}
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1097-0142(19960615)77:12%3C2503::AID-CNCR13%3E3.0.CO;2-W Buzdar et al. 1996 (Protocol 06)]
−
===References===
+
| style="background-color:#1a9851" |Phase III (C)
−
# Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. [https://www.nejm.org/doi/full/10.1056/NEJMoa1100340 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21774708 PubMed]
+
|Fadrozole
−
 
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
−
==LYSA H34==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.2000 Buzdar et al. 1996a]
−
|}
+
| style="background-color:#1a9851" |Phase III (C)
−
===Arm 1===
+
|[[Breast_cancer,_ER-positive#Anastrozole_monotherapy_4|Anastrozole]]
−
*[[Hodgkin_lymphoma#eBEACOPP_2|eBEACOPP]] x 4, then [[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]] x 4
+
| style="background-color:#fc8d59" |Seems to have inferior OS (*)
−
===Arm 2===
 
−
*[[Hodgkin_lymphoma#ABVD_3|ABVD]] x 8
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|BEACOPP<sub>4+4</sub>
+
|[https://www.ejcancer.com/article/0959-8049(96)00191-8/pdf Stuart et al. 1996]
−
|style="background-color:#d9ef8b"|Might have superior EFS
+
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 +
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
−
|ABVD x 8
+
|[https://www.ejcancer.com/article/S0959-8049(97)00105-6/pdf Thürlimann et al. 1997 (SAKK 20/90)]
−
|style="background-color:#fee08b"|Might have inferior EFS
+
| style="background-color:#1a9851" |Phase III (C)
 +
|[[#Formestane_monotherapy|Formestane]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 
|-
 
|-
−
|}
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.7.2494 Russell et al. 1997 (SWOG S8312)]
−
===References===
+
| style="background-color:#1a9851" |Phase III (C)
−
# Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, Gabarre J, Casasnovas O, Jaubert J, Colin P, Delmer A, Devidas A, Bachy E, Nicolas-Virelizier E, Aoudjhane A, Humbrecht C, Andre M, Carde P; Lymphoma Study Association (LYSA). ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug;25(8):1622-8. Epub 2014 May 14. [http://annonc.oxfordjournals.org/content/25/8/1622.full.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24827123 PubMed]
+
|Aminoglutethimide, Hydrocortisone, Megestrol
−
 
+
| style="background-color:#ffffbf" |Seems not superior
−
==NCIC CTG/ECOG HD.6==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|rowspan=2|[https://ascopubs.org/doi/10.1200/JCO.1998.16.2.453 Dombernowsky et al. 1998]
−
|}
+
|rowspan=2 style="background-color:#1a9851"|Randomized (C)
−
''Note: this randomization was for patients with unfavorable risk.''
+
|[[Breast_cancer,_ER-positive#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day
−
===Arm 1===
+
| style="background-color:#d3d3d3" |Not reported
−
*[[Hodgkin_lymphoma#ABVD_2|ABVD]] x 4
 
−
===Arm 2===
 
−
*[[Hodgkin_lymphoma#ABVD_2|ABVD]] x 2, then [[Hodgkin_lymphoma#Radiotherapy_2|STNI]]
 
−
===Comparative efficacy===
 
−
''Efficacy is based on the 2011 update.''
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|ABVD x 4
+
|[[Breast_cancer,_ER-positive#Letrozole_monotherapy_4|Letrozole]]; 2.5 mg/day
−
|style="background-color:#91cf60"|Seems to have superior OS
+
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
−
|ABVD x 2, then STNI
+
|[https://ascopubs.org/doi/full/10.1200/JCO.1999.17.1.52 Goss et al. 1999]
−
|style="background-color:#fc8d59"|Seems to have inferior OS
+
| style="background-color:#1a9851" |Phase III (C)
 +
|Vorozole
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
|-
 
|-
−
|}
+
|[https://ascopubs.org/doi/10.1200/jco.1999.17.1.64 Abrams et al. 1999 (CALGB 8741)]
−
===References===
+
| style="background-color:#1a9851" |Phase III (C)
−
# Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Bezjak A, Wells WA, Burns BF, Winter JN, Horning SJ, Dar AR, Djurfeldt MS, Ding K, Shepherd LE; National Cancer Institute of Canada Clinical Trials Group; Eastern Cooperative Oncology Group. Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol. 2005 Jul 20;23(21):4634-42. Epub 2005 Apr 18. [https://ascopubs.org/doi/10.1200/JCO.2005.09.085 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15837968 PubMed]
+
|[[#Megestrol_monotherapy|Megestrol]]; higher-dose
−
## '''Update:''' Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; Eastern Cooperative Oncology Group. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. Epub 2011 Dec 11. [https://www.nejm.org/doi/full/10.1056/NEJMoa1111961 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932020/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22149921 PubMed]
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
−
 
 
−
=[[Mantle cell lymphoma]]=
 
−
==MCL Younger==
 
−
===Arm 1 (Control)===
 
−
*[[Mantle_cell_lymphoma#R-CHOP|R-CHOP]] x 6, then [[Stem_cell_mobilization#DexaBEAM_.26_G-CSF|Dexa-BEAM]], then [[Mantle_cell_lymphoma#Cyclophosphamide_.26_TBI.2C_then_auto_HSCT|Cy/TBI auto HSCT]]
 
−
===Arm 2 (Experimental)===
 
−
*[[Mantle_cell_lymphoma#R-CHOP.2FR-DHAP|R-CHOP/R-DHAP]] x 6, then cytarabine, melphalan, TBI auto HSCT
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 50%"|Regimen
 
−
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|SOC
+
|[https://ascopubs.org/doi/full/10.1200/JCO.2000.18.7.1399 Kaufmann et al. 2000]
−
| style="background-color:#fc8d59" |Seems to have inferior TTTF
+
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer,_ER-positive#Exemestane_monotherapy_3|Exemestane]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
−
|Cytarabine-based
+
|[https://ascopubs.org/doi/full/10.1200/JCO.2001.19.14.3357 Buzdar et al. 2001]
−
|style="background-color:#91cf60"|Seems to have superior TTTF
+
| style="background-color:#1a9851"|Phase III (C)
 +
|1. [[#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day<br> 2. [[#Letrozole_monotherapy_4|Letrozole]]; 2.5 mg/day
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
|-
 
|-
 
|}
 
|}
−
===References===
+
''Note: Reported efficacy for Jonat et al. 1996 & Buzdar et al. 1996a is based on the 1998 pooled update.''
−
# Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, Szymczyk M, Bouabdallah R, Kneba M, Hallek M, Salles G, Feugier P, Ribrag V, Birkmann J, Forstpointner R, Haioun C, Hänel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Dührsen U, Metzner B, Maschmeyer G, Kanz L, Schmidt C, Delarue R, Brousse N, Klapper W, Macintyre E, Delfau-Larue MH, Pott C, Hiddemann W, Unterhalt M, Dreyling M; European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016 Aug 6;388(10044):565-75. Epub 2016 Jun 14. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00739-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27313086 PubMed]
+
====Hormonotherapy====
 +
*[[Megestrol (Megace)]] 160 mg PO once per day
 +
**Kaufmann et al. 2000 gave as 40 mg PO four times per day
 +
 
 +
'''Continued indefinitely'''
  
−
=[[Multiple myeloma]]=
 
−
==HOVON-50==
 
−
===Arm 1 (Control)===
 
−
*[[Multiple_myeloma_-_historical#VAD|VAD]], then [[Stem_cell_mobilization#CAD_.26_G-CSF|CAD & G-CSF stem cell mobilization]], then [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|single]] or [[Multiple_myeloma,_consolidation_and_maintenance#Tandem_melphalan.2C_then_auto_HSCT|tandem]] melphalan auto HSCT, then [[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|interferon alfa maintenance]]
 
−
===Arm 2 (Experimental)===
 
−
*[[Multiple_myeloma,_induction#TAD_.28Thalidomide.29|TAD]] x 3, then [[Stem_cell_mobilization#CAD_.26_G-CSF|CAD & G-CSF stem cell mobilization]], then [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan.2C_then_auto_HSCT|single]] or [[Multiple_myeloma,_consolidation_and_maintenance#Tandem_melphalan.2C_then_auto_HSCT|tandem]] melphalan auto HSCT, then [[Multiple_myeloma,_consolidation_and_maintenance#Thalidomide_monotherapy|thalidomide maintenance]]
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 50%"|Regimen
 
−
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|SOC
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|Thalidomide-based
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|-
 
−
|}
 
 
===References===
 
===References===
−
# Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group (HOVON). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. [http://www.bloodjournal.org/content/115/6/1113 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19880501 PubMed]
+
# Muss HB, Wells HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, Powell BL, Richards F, White DR, Zekan PJ, Spurr CL, Pope E, Case D, Morgan TM. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1988 Jul;6(7):1098-106. [https://ascopubs.org/doi/abs/10.1200/JCO.1988.6.7.1098 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3292710 PubMed]
−
## '''Update:''' van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30149-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30290905 PubMed]
+
# Lundgren S, Gundersen S, Klepp R, Lønning PE, Lund E, Kvinnsland S. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Res Treat. 1989 Nov;14(2):201-6. [https://link.springer.com/article/10.1007/BF01810736 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2690972 PubMed]
 +
# Muss HB, Case LD, Capizzi RL, Cooper MR, Cruz J, Jackson D, Richards F 2nd, Powell BL, Spurr CL, White D, Zekan P, Read S, Cates-Wilkie S, Bearden J, McCullough J, Callahan R, Karb K, Atkins J, Paschal B, Ramseur B, Lusk J, Stanley V. High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1990 Nov;8(11):1797-805. [https://ascopubs.org/doi/10.1200/jco.1990.8.11.1797 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2230868 PubMed]
 +
# Gill PG, Gebski V, Snyder R, Burns I, Levi J, Byrne M, Coates A. Randomized comparison of the effects of tamoxifen, megestrol acetate, or tamoxifen plus megestrol acetate on treatment response and survival in patients with metastatic breast cancer. Ann Oncol. 1993 Nov;4(9):741-4. [https://academic.oup.com/annonc/article-abstract/4/9/741/170864 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8280654 PubMed]
 +
# Jonat W, Howell A, Blomqvist C, Eiermann W, Winblad G, Tyrrell C, Mauriac L, Roche H, Lundgren S, Hellmund R, Azab M. A randomised trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer. Eur J Cancer. 1996 Mar;32A(3):404-12. [https://www.ejcancer.com/article/0959-8049(95)00014-3/pdf link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8814682 PubMed]
 +
## '''Pooled update:''' Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.2000 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8683230 PubMed]
 +
## '''Pooled update:''' Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. [https://onlinelibrary.wiley.com/doi/full/10.1002/%28SICI%291097-0142%2819980915%2983%3A6%3C1142%3A%3AAID-CNCR13%3E3.0.CO%3B2-5 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9740079 PubMed]
 +
# Buzdar AU, Smith R, Vogel C, Bonomi P, Keller AM, Favis G, Mulagha M, Cooper J. Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: results of two randomized double blind controlled multiinstitutional trials. Cancer. 1996 Jun 15;77(12):2503-13. [https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1097-0142(19960615)77:12%3C2503::AID-CNCR13%3E3.0.CO;2-W link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8640699 PubMed]
 +
# Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.2000 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8683230 PubMed]
 +
## '''Update:''' Buzdar AU, Jones SE, Vogel CL, Wolter J, Plourde P, Webster A; Arimidex Study Group. A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Cancer. 1997 Feb 15;79(4):730-9. [https://onlinelibrary.wiley.com/doi/full/10.1002/%28SICI%291097-0142%2819970215%2979%3A4%3C730%3A%3AAID-CNCR10%3E3.0.CO%3B2-0 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9024711 PubMed]
 +
## '''Pooled update:''' Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. [https://onlinelibrary.wiley.com/doi/full/10.1002/%28SICI%291097-0142%2819980915%2983%3A6%3C1142%3A%3AAID-CNCR13%3E3.0.CO%3B2-5 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9740079 PubMed]
 +
# Stuart NS, Warwick J, Blackledge GR, Spooner D, Keen C, Taylor AR, Tyrell C, Webster DJ, Earl H. A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer. Eur J Cancer. 1996 Oct;32A(11):1888-92. [https://www.ejcancer.com/article/0959-8049(96)00191-8/pdf link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8943670 PubMed]
 +
# '''SAKK 20/90:''' Thürlimann B, Castiglione M, Hsu-Schmitz SF, Cavalli F, Bonnefoi H, Fey MF, Morant R, Löhnert T, Goldhirsch A; Swiss Group for Clinical Cancer Research (SAKK). Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Eur J Cancer. 1997 Jun;33(7):1017-24. [https://www.ejcancer.com/article/S0959-8049(97)00105-6/pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9376181 PubMed]
 +
# '''SWOG S8312:''' Russell CA, Green SJ, O'Sullivan J, Hynes HE, Budd GT, Congdon JE, Martino S, Osborne CK. Megestrol acetate and aminoglutethimide/hydrocortisone in sequence or in combination as second-line endocrine therapy of estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group phase III trial. J Clin Oncol. 1997 Jul;15(7):2494-501. [https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.7.2494 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9215817 PubMed]
 +
# Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J, Bezwoda W, Gardin G, Gudgeon A, Morgan M, Fornasiero A, Hoffmann W, Michel J, Hatschek T, Tjabbes T, Chaudri HA, Hornberger U, Trunet PF. Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol. 1998 Feb;16(2):453-61. [https://ascopubs.org/doi/10.1200/JCO.1998.16.2.453 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9469328 PubMed]
 +
# Goss PE, Winer EP, Tannock IF, Schwartz LH; North American Vorozole Study Group. Randomized phase III trial comparing the new potent and selective third-generation aromatase inhibitor vorozole with megestrol acetate in postmenopausal advanced breast cancer patients. J Clin Oncol. 1999 Jan;17(1):52-63. [https://ascopubs.org/doi/full/10.1200/JCO.1999.17.1.52 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10458218 PubMed]
 +
# '''CALGB 8741:''' Abrams J, Aisner J, Cirrincione C, Berry DA, Muss HB, Cooper MR, Henderson IC, Panasci L, Kirshner J, Ellerton J, Norton L. Dose-response trial of megestrol acetate in advanced breast cancer: Cancer and Leukemia Group B phase III study 8741. J Clin Oncol. 1999 Jan;17(1):64-73. [https://ascopubs.org/doi/10.1200/jco.1999.17.1.64 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10458219 PubMed]
 +
# Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Zilembo N, Dugardyn JL, Nasurdi C, Mennel RG, Cervek J, Fowst C, Polli A, di Salle E, Arkhipov A, Piscitelli G, Miller LL, Massimini G; The Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. J Clin Oncol. 2000 Apr;18(7):1399-411. [https://ascopubs.org/doi/full/10.1200/JCO.2000.18.7.1399 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10735887 PubMed]
 +
# Buzdar A, Douma J, Davidson N, Elledge R, Morgan M, Smith R, Porter L, Nabholtz J, Xiang X, Brady C. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol. 2001 Jul 15;19(14):3357-66. [https://ascopubs.org/doi/full/10.1200/JCO.2001.19.14.3357 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11454883 PubMed]
  
−
=[[Non-small cell lung cancer]]=
+
==Melphalan monotherapy {{#subobject:b913c5|Regimen=1}}==
−
==CONVINCE==
 
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Control)===
+
P: '''<u>P</u>'''henylalanine mustard (Melphalan)
−
*[[Non-small_cell_lung_cancer#Cisplatin_.26_Pemetrexed_3|Cis-Pem]] x 4, then [[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_2|Pemetrexed maintenance]]
+
===Regimen {{#subobject:ab3663|Variant=1}}===
−
===Arm 2 (Experimental)===
 
−
*[[Non-small_cell_lung_cancer,_EGFR-mutated#Icotinib_monotherapy|Icotinib]]
 
−
 
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Cis-Pem, then Pem
+
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197611)38:5%3C1882::AID-CNCR2820380503%3E3.0.CO;2-H Canellos et al. 1976]
−
| style="background-color:#d73027" |Inferior PFS
+
| style="background-color:#1a9851" |Phase III (C)
−
|-
+
|[[Breast_cancer#CMF_2|CMF]]
−
|Icotinib
+
| style="background-color:#fc8d59" |Seems to have inferior OS
−
| style="background-color:#1a9850" |Superior PFS
 
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Melphalan (Alkeran)]] 6 mg/m<sup>2</sup> PO once per day on days 1 to 5
 +
 +
'''42-day cycles'''
 
===References===
 
===References===
−
# Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP, Ding CM, Song X, Ma ZY, Ren XL, Feng JF, Zhang HL, Chen GY, Han XH, Wu N, Yao C, Song Y, Zhang SC, Song W, Liu XQ, Zhao SJ, Lin YC, Ye XQ, Li K, Shu YQ, Ding LM, Tan FL, Sun Y. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study. Ann Oncol. 2017 Oct 1;28(10):2443-2450. [https://academic.oup.com/annonc/article/28/10/2443/4091563 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28945850 PubMed]
+
# Canellos GP, Pocock SJ, Taylor SG 3rd, Sears ME, Klaasen DJ, Band PR. Combination chemotherapy for metastatic breast carcinoma: prospective comparison of multiple drug therapy with L-phenylalanine mustard. Cancer. 1976 Nov;38(5):1882-6. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197611)38:5%3C1882::AID-CNCR2820380503%3E3.0.CO;2-H link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/991103 PubMed]
  
−
==ECOG 3598==
+
==Methotrexate & Thiotepa {{#subobject:c67a88|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Control)===
+
===Regimen {{#subobject:4c1582|Variant=1}}===
−
*[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|PC]] induction, then [[Non-small_cell_lung_cancer#Carboplatin.2C_Paclitaxel.2C_RT|Carboplatin, Paclitaxel, RT]]
+
{| class="wikitable" style="width: 50%; text-align:center;"  
−
===Arm 2, with thalidomide (Experimental)===
+
!style="width: 25%"|Study
−
*TPC, then Carboplatin, Paclitaxel, Thalidomide, RT
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Without thalidomide
 
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
−
|With thalidomide
+
|[https://www.ncbi.nlm.nih.gov/pubmed/13950199 Greenspan et al. 1963]
−
|style="background-color:#ffffbf"|Seems not superior
+
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
 
|}
 
|}
 +
''Note: this is possibly the first published trial of combination chemotherapy in breast cancer.''
 +
====Chemotherapy====
 +
*[[Methotrexate (MTX)]]
 +
*[[Thiotepa (Tepadina)]]
 +
 
===References===
 
===References===
−
# Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, Johnson DH. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012 Feb 20;30(6):616-22. Epub 2012 Jan 23. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.9116 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295560/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22271472 PubMed]
+
# Greenspan EM, Fieber M, Lesnick G, Edelman S. Response of advanced breast carcinoma to the combination of the antimetabolite, Methotrexate, and the alkylating agent, thio-TEPA. J Mt Sinai Hosp N Y. 1963 May-Jun;30:246-67. [https://www.ncbi.nlm.nih.gov/pubmed/13950199 PubMed]  
  
−
==ECOG E4599==
+
==Mitoxantrone monotherapy {{#subobject:c67f55|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Control)===
+
===Regimen {{#subobject:4c8527|Variant=1}}===
−
*[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_4|Carboplatin & Paclitaxel]] x 6
 
−
===Arm 2, with bevacizumab (Experimental)===
 
−
*[[Non-small_cell_lung_cancer#Carboplatin.2C_Paclitaxel.2C_Bevacizumab|PacCBev]] x 6, then [[Non-small_cell_lung_cancer#Bevacizumab_monotherapy|bevacizumab maintenance]]
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Platinum doublet
+
|[https://www.thelancet.com/journals/lancet/article/PII0140-6736(90)90277-C/fulltext Harris et al. 1990]
−
| style="background-color:#d73027" |Inferior OS
+
| style="background-color:#91cf61" |Non-randomized portion of RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|With bevacizumab
+
|[https://academic.oup.com/jnci/article-abstract/83/15/1077/882648 Cowan et al. 1991 (SWOG S8203)]
−
| style="background-color:#1a9850" |Superior OS
+
| style="background-color:#1a9851" |Phase III (C)
 +
|1. Bisantrene<br> 2. [[Breast_cancer#Doxorubicin_monotherapy_3|Doxorubicin]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Mitoxantrone (Novantrone)]] 14 mg/m<sup>2</sup> IV once on day 1
 +
 +
'''21-day cycles'''
 +
 
===References===
 
===References===
−
# Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. [https://www.nejm.org/doi/full/10.1056/NEJMoa061884 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17167137 PubMed]
+
# Harris AL, Cantwell BM, Carmichael J, Wilson R, Farndon J, Dawes P, Ghani S, Evans RG. Comparison of short-term and continuous chemotherapy (mitozantrone) for advanced breast cancer. Lancet. 1990 Jan 27;335(8683):186-90. [https://www.thelancet.com/journals/lancet/article/PII0140-6736(90)90277-C/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1967666 PubMed]
−
## '''Subgroup analysis:''' Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008 Jan 1;26(1):60-5. [http://jco.ascopubs.org/content/26/1/60.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18165641 PubMed]
+
# '''SWOG S8203:''' Cowan JD, Neidhart J, McClure S, Coltman CA Jr, Gumbart C, Martino S, Hutchins LF, Stephens RL, Vaughan CB, Osborne CK. Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study. J Natl Cancer Inst. 1991 Aug 7;83(15):1077-84. [https://academic.oup.com/jnci/article-abstract/83/15/1077/882648 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1875415 PubMed]
  
−
==IUNO==
+
==STAMP-I {{#subobject:c08ab4|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, "early" erlotinib===
+
===Regimen {{#subobject:7gy709|Variant=1}}===
−
*[[Non-small_cell_lung_cancer#Erlotinib_monotherapy|Maintenance erlotinib]]
+
{| class="wikitable" style="width: 100%; text-align:center;"
−
===Arm 2, "late" erlotinib===
+
!style="width: 25%"|Study
−
*[[Non-small_cell_lung_cancer#Placebo_3|Placebo]] until progression or intolerance, then [[Non-small_cell_lung_cancer#Erlotinib_monotherapy_2|erlotinib]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
===Comparative efficacy===
+
!style="width: 25%"|Comparator
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
!'''Timing'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|Maintenance erlotinib
+
|[https://www.nature.com/articles/1705367 Vredenburgh et al. 2006]
−
|style="background-color:#ffffbf"|Seems not superior
+
|style="background-color:#1a9851" |Phase III (E-esc)
−
|-
+
|Observation
−
|Second-line erlotinib
+
| style="background-color:#1a9850" |Superior EFS
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
−
===References===
+
====Preceding treatment====
−
# Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. [http://www.lungcancerjournal.info/article/S0169-5002(16)30504-9/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27987585 PubMed]
+
*Duke AFM x 2 to 4
 +
====Chemotherapy====
 +
*[[Carmustine (BCNU)]]
 +
*[[Cisplatin (Platinol)]]
 +
*[[Cyclophosphamide (Cytoxan)]]
  
−
==KEYNOTE-021==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1 (Control)===
 
−
*[[Non-small_cell_lung_cancer#Carboplatin_.26_Pemetrexed_2|Carbo-Pem]] x 4, then [[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_2|pemetrexed maintenance]]
 
−
===Arm 2, with pembrolizumab (Experimental)===
 
−
*[[Non-small_cell_lung_cancer#Carboplatin.2C_Pemetrexed.2C_Pembrolizumab|Carboplatin, Pemetrexed, Pembrolizumab]] x 4, then [[Non-small_cell_lung_cancer#Pemetrexed_.26_Pembrolizumab|Pemetrexed & Pembrolizumab maintenance]]
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Control
 
−
| style="background-color:#d73027" |Inferior ORR
 
−
|-
 
−
|Experimental (with pembrolizumab)
 
−
|style="background-color:#1a9850"|Superior ORR
 
−
|-
 
−
|}
 
 
===References===
 
===References===
−
# Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, Gentzler RD, Martins RG, Stevenson JP, Jalal SI, Panwalkar A, Yang JC, Gubens M, Sequist LV, Awad MM, Fiore J, Ge Y, Raftopoulos H, Gandhi L; KEYNOTE-021 investigators. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016 Nov;17(11):1497-1508. Epub 2016 Oct 10. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30498-3/fulltext link to original article] [http://thelancet.com/cms/attachment/2074509559/2069027402/mmc1.pdf supplementary appendix] [https://www.ncbi.nlm.nih.gov/pubmed/27745820 PubMed]
+
# Vredenburgh JJ, Madan B, Coniglio D, Ross M, Broadwater G, Niedzwiecki D, Edwards J, Marks L, Vandemark R, McDonald C, Affronti ML, Peters WP. A randomized phase III comparative trial of immediate consolidation with high-dose chemotherapy and autologous peripheral blood progenitor cell support compared to observation with delayed consolidation in women with metastatic breast cancer and only bone metastases following intensive induction chemotherapy. Bone Marrow Transplant. 2006 Jun;37(11):1009-15. [https://www.nature.com/articles/1705367 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16633363 PubMed]
  
−
==KEYNOTE-189==
+
==TAD (Tamoxifen) {{#subobject:1ac555|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Control)===
+
TAD: '''<u>T</u>'''amoxifen, '''<u>A</u>'''minoglutethimide, '''<u>D</u>'''anazol
−
*Investigator's choice of:
+
===Regimen {{#subobject:0b2c27|Variant=1}}===
−
**[[Non-small_cell_lung_cancer#Carboplatin_.26_Pemetrexed_2|Carbo-Pem]] x 4, then [[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_2|pemetrexed maintenance]]
 
−
**[[Non-small_cell_lung_cancer#Cisplatin_.26_Pemetrexed_3|Cis-Pem]] x 4, then [[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_2|pemetrexed maintenance]]
 
−
===Arm 2, with pembrolizumab (Experimental)===
 
−
*Investigator's choice of:
 
−
**[[Non-small_cell_lung_cancer#Carboplatin.2C_Pemetrexed.2C_Pembrolizumab|Carboplatin, Pemetrexed, Pembrolizumab]] x 4, then [[Non-small_cell_lung_cancer#Pemetrexed_.26_Pembrolizumab|Pemetrexed & Pembrolizumab maintenance]]
 
−
**[[Non-small_cell_lung_cancer#Cisplatin.2C_Pemetrexed.2C_Pembrolizumab|Cisplatin, Pemetrexed, Pembrolizumab]] x 4, then [[Non-small_cell_lung_cancer#Pemetrexed_.26_Pembrolizumab|Pemetrexed & Pembrolizumab maintenance]]
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
|-
+
!style="width: 25%"|Comparator
−
|Control
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
| style="background-color:#d73027" |Inferior OS
 
 
|-
 
|-
−
|Experimental (with pembrolizumab)
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)91872-5/fulltext Powles et al. 1984]
−
|style="background-color:#1a9850"|Superior OS
+
| style="background-color:#1a9851" |Phase III (E-esc)
 +
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
 +
| style="background-color:#91cf60" |Seems to have superior ORR
 
|-
 
|-
 
|}
 
|}
 +
''Note: this patient population was not selected by hormone receptor status.''
 +
====Hormonotherapy====
 +
*[[Tamoxifen (Nolvadex)]]
 +
*[[Aminoglutethimide (Cytadren)]]
 +
*[[Danazol (Danocrine)]]
 
===References===
 
===References===
−
# Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. Epub 2018 Apr 16. [https://www.nejm.org/doi/full/10.1056/NEJMoa1801005 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1801005/suppl_file/nejmoa1801005_protocol.pdf link to protocol] [https://www.ncbi.nlm.nih.gov/pubmed/29658856 PubMed]
+
# Powles TJ, Ashley S, Ford HT, Gazet JC, Nash AG, Neville AM, Coombes RC. Treatment of disseminated breast cancer with tamoxifen, aminoglutethimide, hydrocortisone, and danazol, used in combination or sequentially. Lancet. 1984 Jun 23;1(8391):1369-73. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)91872-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6145832 PubMed]
  
−
==KEYNOTE-407==
+
==Thiotepa monotherapy {{#subobject:123f55|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1 (Control)===
+
===Regimen {{#subobject:4a8d27|Variant=1}}===
−
*Investigator's choice of:
+
{| class="wikitable" style="width: 50%; text-align:center;"  
−
**[[Non-small_cell_lung_cancer#Carboplatin_.26_nab-Paclitaxel|Carboplatin & nab-Paclitaxel]] x 4
+
!style="width: 25%"|Study
−
**[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_6|CP]] x 4
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
===Arm 2, with pembrolizumab (Experimental)===
 
−
*Investigator's choice of:
 
−
**[[Non-small_cell_lung_cancer#Carboplatin.2C_nab-Paclitaxel.2C_Pembrolizumab|Carboplatin, nab-Paclitaxel, Pembrolizumab]] x 4, then [[Non-small_cell_lung_cancer#Pembrolizumab_monotherapy_2|Pembrolizumab maintenance]]
 
−
**[[Non-small_cell_lung_cancer#Carboplatin.2C_Paclitaxel.2C_Pembrolizumab|Carboplatin, Paclitaxel, Pembrolizumab]] x 4, then [[Non-small_cell_lung_cancer#Pembrolizumab_monotherapy_2|Pembrolizumab maintenance]]
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Control
 
−
| style="background-color:#d73027" |Inferior OS
 
 
|-
 
|-
−
|Experimental (with pembrolizumab)
+
|[https://www.nejm.org/doi/full/10.1056/NEJM195505262522101 Bateman 1955]
−
|style="background-color:#1a9850"|Superior OS
+
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
 
|}
 
|}
−
===References===
+
====Chemotherapy====
−
# Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, Hermes B, Çay Şenler F, Csőszi T, Fülöp A, Rodríguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM; KEYNOTE-407 Investigators. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. Epub 2018 Sep 25. [https://www.nejm.org/doi/10.1056/NEJMoa1810865 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30280635 PubMed]
+
*[[Thiotepa (Thioplex)]]
  
−
==PRONOUNCE==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1===
 
−
*[[Non-small_cell_lung_cancer#Carboplatin_.26_Pemetrexed_2|Carbo-Pem]] x 4, then [[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_2|pemetrexed maintenance]]
 
−
===Arm 2===
 
−
*[[Non-small_cell_lung_cancer#Carboplatin.2C_Paclitaxel.2C_Bevacizumab_2|PacCBev]] x 4, then [[Non-small_cell_lung_cancer#Bevacizumab_monotherapy|bevacizumab maintenance]]
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Arm 1
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|Arm 2
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|}
 
 
===References===
 
===References===
−
# Zinner RG, Obasaju CK, Spigel DR, Weaver RW, Beck JT, Waterhouse DM, Modiano MR, Hrinczenko B, Nikolinakos PG, Liu J, Koustenis AG, Winfree KB, Melemed SA, Guba SC, Ortuzar WI, Desaiah D, Treat JA, Govindan R, Ross HJ. PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2015 Jan;10(1):134-42. [http://www.jto.org/article/S1556-0864(15)30782-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276572/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25371077 PubMed]
+
# Bateman JC. Chemotherapy of solid tumors with triethylene thiophosphoramide. N Engl J Med. 1955 May 26;252(21):879-87. [https://www.nejm.org/doi/full/10.1056/NEJM195505262522101 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14370446 PubMed]
  
−
==RTOG 9410==
+
==VAC (Adriamycin) {{#subobject:90f8d0|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Arm 1, sequential===
+
VAC: '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
−
*[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinblastine_2|Cisplatin & Vinblastine]], then [[Non-small_cell_lung_cancer#Radiation_therapy|RT]]
+
===Regimen {{#subobject:4da860|Variant=1}}===
−
===Arm 2, concurrent===
 
−
*[[Non-small_cell_lung_cancer#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]]
 
−
===Arm 3, concurrent===
 
−
*[[Non-small_cell_lung_cancer#Cisplatin.2C_Vinblastine.2C_RT|Cisplatin, Vinblastine, RT]]
 
−
===Comparative efficacy===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Schedule'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|Comparator
 +
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|Concurrent
+
|[http://www.sciencedirect.com/science/article/pii/0277537986900751 Gundersen et al. 1986]
−
|style="background-color:#91cf60"|Seems to have superior OS
+
|style="background-color:#1a9851"|Phase III (C)
 +
|[[Breast_cancer#Doxorubicin_monotherapy_2|Doxorubicin]]
 +
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
−
|Sequential
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977504/ Powles et al. 1991]
−
|style="background-color:#fc8d59"|Seems to have inferior OS
+
|style="background-color:#1a9851"|Phase III (C)
 +
|3M
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
|-
 
|-
−
|}
+
|[https://link.springer.com/article/10.1007/BF01806182 Green et al. 1996]
−
===References===
+
|style="background-color:#1a9851"|Phase III (C)
−
# Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. [http://jnci.oxfordjournals.org/content/103/19/1452.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186782/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21903745 PubMed]
+
|VNC
−
 
+
| style="background-color:#d9ef8b" |Might have superior ORR
−
=[[Ovarian cancer]]=
 
−
==GOG 114==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
−
===Arm 1 - Control===
+
''Used as a comparator arm in older trials and found to be more toxic; here for reference purposes only.''
−
*[[Ovarian_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]] x 6
+
====Chemotherapy====
−
===Arm 2 - Experimental===
+
*[[Vincristine (Oncovin)]]
−
*[[Ovarian_cancer#Carboplatin_monotherapy|Carboplatin]] AUC 9 x 2, then [[Ovarian_cancer#Cisplatin_.26_Paclitaxel_2|IP Cisplatin & IV Paclitaxel]] x 6
+
*[[Doxorubicin (Adriamycin)]]
−
===Comparative efficacy===
+
*[[Cyclophosphamide (Cytoxan)]]
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 50%"|'''Regimen'''
 
−
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Control
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|Experimental
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
===References===
 
−
# Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. [https://ascopubs.org/doi/full/10.1200/JCO.2001.19.4.1001 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11181662 PubMed]
 
  
−
==OCEANS==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Arm 1 - Control===
 
−
*[[Ovarian_cancer#Carboplatin_.26_Gemcitabine_2|Carboplatin & Gemcitabine]] x 6 to 10
 
−
===Arm 2 - Experimental===
 
−
*[[Ovarian_cancer#Carboplatin.2C_Gemcitabine.2C_Bevacizumab|Carboplatin, Gemcitabine, Bevacizumab]] x 6 to 10, then [[Ovarian_cancer#Bevacizumab_monotherapy|Bevacizumab maintenance]]
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 50%"|'''Regimen'''
 
−
!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Carbo-Gem
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|With Bevacizumab
 
−
|style="background-color:#1a9850"|Superior PFS
 
−
|-
 
−
|}
 
 
===References===
 
===References===
−
# Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. Epub 2012 Apr 23. [http://jco.ascopubs.org/content/30/17/2039.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646321/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22529265 PubMed]
+
# Gundersen S, Kvinnsland S, Klepp O, Kvaløy S, Lund E, Høst H. Weekly adriamycin versus VAC in advanced breast cancer: a randomized trial. Eur J Cancer Clin Oncol. 1986 Dec;22(12):1431-4. [http://www.sciencedirect.com/science/article/pii/0277537986900751 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/3595668 PubMed]
 +
# Powles TJ, Jones AL, Judson IR, Hardy JR, Ashley SE. A randomised trial comparing combination chemotherapy using mitomycin C, mitozantrone and methotrexate (3M) with vincristine, anthracycline and cyclophosphamide (VAC) in advanced breast cancer. Br J Cancer. 1991 Aug;64(2):406-10. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977504/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1892775 PubMed]
 +
# Green JA, Slater AJ, Campbell IR, Kelly V. Advanced breast cancer: a randomized study of doxorubicin or mitoxantrone in combination with cyclophosphamide and vincristine. Breast Cancer Res Treat. 1996;39(2):155-63. [https://link.springer.com/article/10.1007/BF01806182 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8872324 PubMed]
  
−
=[[Pancreatic cancer]]=
+
==VAP {{#subobject:4b99b8|Regimen=1}}==
−
==GERCOR LAP07==
 
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
''This study had two randomizations; the second only occurred if patients were progression-free after 4 cycles.''
+
VAP: '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''rednisolone
−
===Arm 1 - Control===
+
===Regimen {{#subobject:7d4b85|Variant=1}}===
−
*[[Pancreatic_cancer#Gemcitabine_monotherapy_2|Gemcitabine]] x 6
 
−
===Arm 2 - Experimental===
 
−
*[[Pancreatic_cancer#Gemcitabine_monotherapy_2|Gemcitabine]] x 4, then Capecitabine & RT
 
−
===Arm 3 - Experimental===
 
−
*[[Pancreatic_cancer#Erlotinib_.26_Gemcitabine|Erlotinib & Gemcitabine]] x 6
 
−
===Arm 4 - Experimental===
 
−
*[[Pancreatic_cancer#Erlotinib_.26_Gemcitabine|Erlotinib & Gemcitabine]] x 4, then Capecitabine, Erlotinib, RT
 
−
===Comparative efficacy===
 
−
====First randomization====
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!'''Regimen'''
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
|-
+
!style="width: 25%"|Comparator
−
|Gemcitabine
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
|style="background-color:#d9ef8b"|Might have superior OS
 
−
|-
 
−
|With Erlotinib
 
−
|style="background-color:#fee08b"|Might have inferior OS
 
−
|-
 
−
|}
 
−
====Second randomization====
 
−
{| class="wikitable" style="width: 100%; text-align:center;"  
 
−
!'''Modality'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|Chemotherapy
 
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
−
|Chemoradiotherapy
+
|[https://ascopubs.org/doi/abs/10.1200/JCO.1987.5.7.1056 Leonard et al. 1987]
 +
|style="background-color:#1a9851"|Phase III (C)
 +
|VMP
 
|style="background-color:#ffffbf"|Seems not superior
 
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Vincristine (Oncovin)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
====Hormonotherapy====
 +
*[[Prednisolone (Millipred)]]
 
===References===
 
===References===
−
# Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; LAP07 Trial Group. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. [https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.4324 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27139057 PubMed]
+
# Leonard RC, Cornbleet MA, Kaye SB, Soukop M, White G, Hutcheon AW, Robinson S, Kerr ME, Smyth JF. Mitoxantrone versus doxorubicin in combination chemotherapy for advanced carcinoma of the breast. J Clin Oncol. 1987 Jul;5(7):1056-63. [https://ascopubs.org/doi/abs/10.1200/JCO.1987.5.7.1056 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3298559 PubMed]
−
 
 
−
=[[Small cell lung cancer]]=
 
−
==IMpower133==
 
−
===Arm 1 (Control)===
 
−
[[Small_cell_lung_cancer#Carboplatin_.26_Etoposide_2|CE]] x 4
 
−
 
 
−
===Arm 2 (Experimental)===
 
−
[[Small_cell_lung_cancer#Carboplatin.2C_Etoposide.2C_Atezolizumab|CE & Atezolizumab]] x 4, then [[Small_cell_lung_cancer#Atezolizumab_maintenance|Atezolizumab maintenance]]
 
−
===Comparative efficacy===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!'''Regimen'''
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|With atezolizumab
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|Without atezolizumab
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
===References===
 
−
# Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Sep 25. [Epub ahead of print] [https://www.nejm.org/doi/full/10.1056/NEJMoa1809064 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30280641 PubMed]
 
  
−
[[Category:General reference pages]]
+
[[Category:Breast cancer regimens]]
 +
[[Category:Historical regimens]]
 +
[[Category:Disease-specific pages]]
 +
[[Category:Solid tumors]]

Revision as of 03:29, 14 December 2019

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main breast cancer page for current regimens.

0 regimens on this page
0 variants on this page


Neoadjuvant therapy

CVAP

back to top

CVAP: Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), Prednisolone
VACP: Vincristine, Adriamycin (Doxorubicin), Cyclophosphamide, Prednisolone

Regimen

Study Evidence
Smith et al. 2002 Non-randomized portion of RCT
Thomas E et al. 2004 Non-randomized portion of RCT

Chemotherapy

Hormonotherapy

Subsequent treatment

References

  1. Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, Ah-See AK, Eremin O, Walker LG, Sarkar TK, Eggleton SP, Ogston KN. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol. 2002 Mar 15;20(6):1456-66. link to original article PubMed
  2. Thomas E, Holmes FA, Smith TL, Buzdar AU, Frye DK, Fraschini G, Singletary SE, Theriault RL, McNeese MD, Ames F, Walters R, Hortobagyi GN. The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol. 2004 Jun 15;22(12):2294-302. link to original article PubMed

Epirubicin monotherapy

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Bottini et al. 2005 Phase III (C) Epirubicin & Tamoxifen Seems not superior

Chemotherapy

Subsequent treatment

References

  1. Bottini A, Berruti A, Brizzi MP, Bersiga A, Generali D, Allevi G, Aguggini S, Bolsi G, Bonardi S, Tondelli B, Vana F, Tampellini M, Alquati P, Dogliotti L. Cytotoxic and antiproliferative activity of the single agent epirubicin versus epirubicin plus tamoxifen as primary chemotherapy in human breast cancer: a single-institution phase III trial. Endocr Relat Cancer. 2005 Jun;12(2):383-92. link to original article PubMed

Adjuvant therapy

ACT

back to top

ACT: Adriamycin (Doxorubicin), Cyclophosphamide, Tamoxifen

Regimen

Study Evidence Comparator Comparative Efficacy
Fisher et al. 1990 (NSABP B-16) Phase III (E-esc) 1. PFT Not reported
2. Tamoxifen Seems to have superior OS
Shien et al. 2014 (JCOG9401) Phase III (E-esc) Tamoxifen Seems to have superior RFS
Shien et al. 2014 (JCOG9404) Phase III (E-de-esc) TUFT Seems not superior

Preceding treatment

Chemotherapy

Hormonotherapy

References

  1. NSABP B-16: Fisher B, Redmond C, Legault-Poisson S, Dimitrov NV, Brown AM, Wickerham DL, Wolmark N, Margolese RG, Bowman D, Glass AG, Kardinal CG, Robidoux A, Jochimsen P, Cronin W, Deutsch M, Fisher ER, Myers DB, Hoehn JL. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990 Jun;8(6):1005-18. link to original article PubMed
    1. Pooled update: Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. link to original article PubMed
  2. JCOG9401: Shien T, Iwata H, Aogi K, Fukutomi T, Inoue K, Kinoshita T, Takahashi M, Matsui A, Shibata T, Fukuda H. Tamoxifen versus tamoxifen plus doxorubicin and cyclophosphamide as adjuvant therapy for node-positive postmenopausal breast cancer: results of a Japan Clinical Oncology Group Study (JCOG9401). Int J Clin Oncol. 2014 Dec;19(6):982-8. Epub 2014 Jan 7. link to original article PubMed
  3. JCOG9404: Shien T, Iwata H, Fukutomi T, Inoue K, Aogi K, Kinoshita T, Ando J, Takashima S, Nakamura K, Shibata T, Fukuda H. Tamoxifen plus tegafur-uracil (TUFT) versus tamoxifen plus Adriamycin (doxorubicin) and cyclophosphamide (ACT) as adjuvant therapy to treat node-positive premenopausal breast cancer (PreMBC): results of Japan Clinical Oncology Group Study 9404. Cancer Chemother Pharmacol. 2014 Sep;74(3):603-9. Epub 2014 Jul 24. link to original article link to PMC article PubMed

AVCF

back to top

AVCF: Adriamycin (Doxorubicin), Vincristine, Cyclophosphamide, Fluorouracil

Regimen

Study Evidence Comparator Comparative Efficacy
Misset et al. 1996 (OncoFrance) Phase III (E-RT-esc) CMF Superior OS

Preceding treatment

Chemotherapy

References

  1. OncoFrance: Misset JL, di Palma M, Delgado M, Plagne R, Chollet P, Fumoleau P, Le Mevel B, Belpomme D, Guerrin J, Fargeot P, Metz R, Ithzaki M, Hill C, Mathé G. Adjuvant treatment of node-positive breast cancer with cyclophosphamide, doxorubicin, fluorouracil, and vincristine versus cyclophosphamide, methotrexate, and fluorouracil: final report after a 16-year median follow-up duration. J Clin Oncol. 1996 Apr;14(4):1136-45. link to original article PubMed

AV-CMF

back to top

AV-CMF: Adriamycin (Doxorubicin), Vinblastine, Cyclophosphamide, Methotrexate, Fluorouracil

Regimen

Study Evidence Comparator Comparative Efficacy
Ploner et al. 2003 (ABCSG 3) Randomized (E-RT-esc) CMF Seems not superior

Preceding treatment

Chemotherapy

References

  1. ABCSG 3: Ploner F, Jakesz R, Hausmaninger H, Kolb R, Stierer M, Fridrik M, Steindorfer P, Gnant M, Haider K, Mlineritsch B, Tschurtschenthaler G, Steger G, Seifert M, Kubista E, Samonigg H; Austrian Breast And Colorectal Cancer Study Group. Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive, hormone receptor-negative breast cancer patients. Onkologie. 2003 Apr;26(2):115-9. link to original article PubMed

CAMFP

back to top

CAMFP: Cyclophosphamide, Adriamycin (Doxorubicin), Methotrexate, Fluorouracil, Prednisone

Regimen

Study Evidence Comparator Comparative Efficacy
Recht et al. 1996 Phase III (E-switch-ic) See link See link

Note: this was a trial examining sequencing of chemotherapy and radiotherapy; see text for efficacy details.

Preceding treatment

Chemotherapy

Hormonotherapy

21-day cycle for 4 cycles

References

  1. Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, Shulman LN, Harris JR. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996 May 23;334(21):1356-61. link to original article PubMed

CEF/CMF

back to top

CEF/CMF: Cyclophosphamide, Epirubicin, Fluorouracil alternating with Cyclophosphamide, Methotrexate, Fluorouracil

Regimen

Study Evidence Comparator Comparative Efficacy
Bedognetti et al. 2011 Phase III (C) CEFT/CMFT Seems not superior

Preceding treatment

Chemotherapy, CEF portion

Chemotherapy, CMF portion

References

  1. Bedognetti D, Sertoli MR, Pronzato P, Del Mastro L, Venturini M, Taveggia P, Zanardi E, Siffredi G, Pastorino S, Queirolo P, Gardin G, Wang E, Monzeglio C, Boccardo F, Bruzzi P. Concurrent vs sequential adjuvant chemotherapy and hormone therapy in breast cancer: a multicenter randomized phase III trial. J Natl Cancer Inst. 2011 Oct 19;103(20):1529-39. Epub 2011 Sep 15. link to original article link to PMC article PubMed

CFP

back to top

CFP: Cyclophosphamide, Fluorouracil, Prednisone

Regimen

Study Evidence Comparator Comparative Efficacy
Ahmann et al. 1978 Phase III (E-esc) Melphalan Seems to have superior OS
Caprini et al. 1980 Phase III (E-esc) 1. Melphalan Seems to have superior DFS
2. CFP & BCG Seems not superior

Preceding treatment

Chemotherapy

Hormonotherapy

References

  1. Ahmann DL, Scanlon PW, Bisel HF, Edmonson JH, Frytak S, Payne WS, O'Fallon JR, Hahn RG, Ingle JN, O'Connell MJ, Rubin J. Repeated adjuvant chemotherapy with phenylalanine mustard or 5-fluorouracil, cyclophosphamide, and prednisone with or without radiation, after mastectomy for breast cancer. Lancet. 1978 Apr 29;1(8070):893-6. link to original article PubMed
  2. Caprini JA, Oviedo MA, Cunningham MP, Cohen E, Trueheart RS, Khandekar JD, Scanlon EF. Adjuvant chemotherapy for stage II and III breast carcinoma. JAMA. 1980 Jul 18;244(3):243-6. link to original article PubMed

CFP & Oophorectomy

back to top

CFP & Oophorectomy: Cyclophosphamide, Fluorouracil, Prednisone & Bilateral Oophorectomy

Regimen

Study Evidence Comparator Comparative Efficacy
Ahmann et al. 1977 Phase III (E-esc) Oophorectomy Seems to have superior PFS

Preceding treatment

Chemotherapy

Hormonotherapy

References

  1. Ahmann DL, O'Connell MJ, Hahn RG, Bisel HF, Lee RA, Edmonson JH. An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advanced breast cancer undergoing oophorectomy. N Engl J Med. 1977 Aug 18;297(7):356-60. link to original article PubMed

CMFL

back to top

CMFL: Cyclophosphamide, Methotrexate, Fluorouracil, Leucovorin (Folinic acid)

Regimen

Study Evidence Comparator Comparative Efficacy
Goldhirsch et al. 1989 (LCBS V) Phase III (E-esc) No further treatment Seems to have superior DFS

Preceding treatment

Chemotherapy

8-day course

References

  1. LCBS V: Goldhirsch A, Gelber RD; Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med. 1989 Feb 23;320(8):491-6. link to original article PubMed

CMFP

back to top

CMFP: Cyclophosphamide, Methotrexate, Fluorouracil, Prednisone

Regimen

Study Evidence Comparator Comparative Efficacy
Goldhirsch et al. 1988 (IBCSG V) Phase III (C) CMFL x 1 Seems to have superior OS
Mansour et al. 1989 (INT-0011) Phase III (E-esc) No further treatment Superior DFS
Tormey et al. 1990 (ECOG E5177) Phase III (E-esc) 1. CMF
2. CMFPT 		Seems not superior

Preceding treatment

Chemotherapy

Hormonotherapy

28-day cycle for 6 to 12 cycles

References

  1. IBCSG V: Goldhirsch A; Ludwig Breast Cancer Study Group. Combination adjuvant chemotherapy for node-positive breast cancer: inadequacy of a single perioperative cycle. N Engl J Med. 1988 Sep 15;319(11):677-83. link to original article PubMed
  2. ECOG E1180: Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med. 1989 Feb 23;320(8):485-90. link to original article PubMed
    1. Update: Mansour EG, Eudey L, Tormey DC, Shatila AH, Osborne CK, Gilchrist KW, Cooper MR, Falkson G. Chemotherapy versus observation in high-risk node-negative breast cancer patients. J Natl Cancer Inst Monogr. 1992;(11):97-104. PubMed
  3. ECOG E5177: Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. link to original article PubMed

CMFPT

back to top

CMFPT: Cyclophosphamide, Methotrexate, Fluorouracil, Prednisone, Tamoxifen

Regimen

Study Evidence Comparator Comparative Efficacy
Goldhirsch et al. 1984 (LBCS III) Phase III (E-esc) 1. Observation Superior DFS
2. PT Seems to have superior DFS
Goldhirsch et al. 1988 (IBCSG V) Phase III (C) CMFL x 1 Seems to have superior OS
Tormey et al. 1990 (ECOG E5177) Phase III (E-esc) 1. CMF
2. CMFP 		Seems not superior
Falkson et al. 1990 Phase III (C) CMFPT x 4 Seems not superior

Preceding treatment

Chemotherapy

Hormonotherapy

28-day cycle for 6 to 12 cycles

References

  1. LBCS III/IV: Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. link to original article PubMed
  2. IBCSG V: Goldhirsch A; Ludwig Breast Cancer Study Group. Combination adjuvant chemotherapy for node-positive breast cancer: inadequacy of a single perioperative cycle. N Engl J Med. 1988 Sep 15;319(11):677-83. link to original article PubMed
  3. ECOG E5177: Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. link to original article PubMed
  4. Falkson HC, Gray R, Wolberg WH, Gillchrist KW, Harris JE, Tormey DC, Falkson G. Adjuvant trial of 12 cycles of CMFPT followed by observation or continuous tamoxifen versus four cycles of CMFPT in postmenopausal women with breast cancer: an Eastern Cooperative Oncology Group phase III study. J Clin Oncol. 1990 Apr;8(4):599-607. Erratum in: J Clin Oncol 1990 Sep;8(9):1603. link to original article PubMed

CMFT

back to top

CMFT: Cyclophosphamide, Methotrexate, Fluorouracil, Tamoxifen

Regimen

Study Evidence Comparator Comparative Efficacy
Hubay et al. 1980 Randomized (E-RT-esc) CMF Seems to have superior RFS

Preceding treatment

Chemotherapy

Hormonotherapy

References

  1. Hubay CA, Pearson OH, Marshall JS, Rhodes RS, Debanne SM, Mansour EG, Hermann RE, Jones JC, Flynn WJ, Eckert C, McGuire WL. Antiestrogen, cytotoxic chemotherapy, and bacillus Calmette-Guerin vaccination in stage II breast cancer: a preliminary report. Surgery. 1980 May;87(5):494-501. link to original article PubMed
    1. Update: Hubay CA, Pearson OH, Marshall JS, Rhodes RS, DeBanne SM, Rosenblatt J, Mansour EG, Hermann RE, Jones JC, Flynn WJ, Eckert C, McGuire WL. Adjuvant chemotherapy, antiestrogen therapy and immunotherapy for stage II breast cancer: 45-month follow-up of a prospective, randomized clinical trial. Cancer. 1980 Dec 15;46(12 Suppl):2805-8. link to original article PubMed

CMFVP

back to top

CMFVP: Cyclophosphamide, Methotrexate, Fluorouracil, Vincristine, Prednisone

Regimen

Study Evidence Comparator Comparative Efficacy
Hoogstraten et al. 1976 Phase III (E-esc) Doxorubicin Seems to have superior ORR
Carmo-Pereira et al. 1980 Phase III (E-esc) 5-FU Superior OS
Glucksberg et al. 1982 (SWOG S7436) Phase III (E-esc) Melphalan Superior OS
Tormey et al. 1983a Phase III (E-esc) CMF Superior DFS
CMF-MER Not reported
Rivkin et al. 1993 (SWOG S7827ER-) Phase III (C) CMFVP x 2 y Seems not superior
Budd et al. 1995 (SWOG S8313) Phase III (C) FAC-M Seems not superior
Rivkin et al. 1996 (SWOG S7821) Phase III (C) CMFVP & Oophorectomy Seems not superior

Preceding treatment

Chemotherapy

Hormonotherapy

References

  1. Hoogstraten B, George SL, Samal B, Rivkin SE, Costanzi JJ, Bonnet JD, Thigpen T, Braine H. Combination chemotherapy and adriamycin in patients with advanced breast cancer: a Southwest Oncology Group study. Cancer. 1976 Jul;38(1):13-20. link to original article PubMed
  2. Carmo-Pereira J, Costa FO, Henriques E. Single-drug vs combination cytotoxic chemotherapy in advanced breast cancer: a randomized study. Eur J Cancer. 1980 Dec;16(12):1621-5. link to SD article PubMed
  3. SWOG S7436: Glucksberg H, Rivkin SE, Rasmussen S, Tranum B, Gad-el-Mawla N, Costanzi J, Hoogstraten B, Athens J, Maloney T, McCracken J, Vaughn C. Combination chemotherapy (CMFVP) versus L-phenylalanine mustard (L-PAM) for operable breast cancer with positive axillary nodes: a Southwest Oncology Group Study. Cancer. 1982 Aug 1;50(3):423-34. link to original article PubMed
    1. Update: Rivkin SE, Green SJ, Lew D, Costanzi JJ, Athens JW, Osborne CK, Vaughn CB, Martino S. Adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil, vincristine, and prednisone compared with single-agent L-phenylalanine mustard for patients with operable breast carcinoma and positive axillary lymph nodes: 20-year results of a Southwest Oncology Group study. Cancer. 2003 Jan 1;97(1):21-9. link to original article PubMed
  4. Tormey DC, Weinberg VE, Holland JF, Weiss RB, Glidewell OJ, Perloff M, Falkson G, Falkson HC, Henry PH, Leone LA, Rafla S, Ginsberg SJ, Silver RT, Blom J, Carey RW, Schein PS, Lesnick GJ. A randomized trial of five and three drug chemotherapy and chemoimmunotherapy in women with operable node positive breast cancer. J Clin Oncol. 1983 Feb;1(2):138-45. link to original article PubMed
  5. SWOG S7827: Rivkin SE, Green S, Metch B, Jewell WR, Costanzi JJ, Altman SJ, Minton JP, O'Bryan RM, Osborne CK. One versus 2 years of CMFVP adjuvant chemotherapy in axillary node-positive and estrogen receptor-negative patients: a Southwest Oncology Group study. J Clin Oncol. 1993 Sep;11(9):1710-6. link to original article PubMed
  6. SWOG S8313: Budd GT, Green S, O'Bryan RM, Martino S, Abeloff MD, Rinehart JJ, Hahn R, Harris J, Tormey D, O'Sullivan J, Osborne CK. Short-course FAC-M versus 1 year of CMFVP in node-positive, hormone receptor-negative breast cancer: an intergroup study. J Clin Oncol. 1995 Apr;13(4):831-9. link to original article PubMed
  7. SWOG S7821: Rivkin SE, Green S, O'Sullivan J, Cruz AB, Abeloff MD, Jewell WR, Costanzi JJ, Farrar WB, Osborne CK. Adjuvant CMFVP versus adjuvant CMFVP plus ovariectomy for premenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study. J Clin Oncol. 1996 Jan;14(1):46-51. link to original article PubMed

CPB

back to top

CPB: Cyclophosphamide, Platinol (Cisplatin), BCNU (Carmustine)

Regimen

Study Evidence Comparator Comparative Efficacy
Peters et al. 2005 (CALGB 9082) Phase III (E-de-esc) HD-CPB with auto HSCT Seems not superior

Note: this trial is of important historic significance. Although neither arm was standard of care, the results established the non-value of high-dose therapy with autologous HSCT in the adjuvant treatment of breast cancer.

Preceding treatment

Chemotherapy

References

  1. CALGB 9082: Peters WP, Rosner GL, Vredenburgh JJ, Shpall EJ, Crump M, Richardson PG, Schuster MW, Marks LB, Cirrincione C, Norton L, Henderson IC, Schilsky RL, Hurd DD. Prospective, randomized comparison of high-dose chemotherapy with stem-cell support versus intermediate-dose chemotherapy after surgery and adjuvant chemotherapy in women with high-risk primary breast cancer: a report of CALGB 9082, SWOG 9114, and NCIC MA-13. J Clin Oncol. 2005 Apr 1;23(10):2191-200. Epub 2005 Mar 14. link to original article PubMed

CTCb, then auto HSCT

back to top

CTCb: Cyclophosphamide, Thiotepa, Carboplatin
STAMP-V

Regimen

Study Evidence Comparator Comparative Efficacy
Eder et al. 1990 Phase I/II
Rodenhuis et al. 1998 Randomized Phase II (E-esc) Standard adjuvant therapy Seems not superior
Bergh et al. 2000 (SBG 9401) Phase III (C) See link See link
Rodenhuis et al. 2003 Phase III (E-esc) FEC x 5 Might have superior RFS

No longer used, but of historical interest.

Preceding treatment

Chemotherapy

Stem cells re-infused on day 0

References

  1. Eder JP, Elias A, Shea TC, Schryber SM, Teicher BA, Hunt M, Burke J, Siegel R, Schnipper LE, Frei E 3rd, Antman K. A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients. J Clin Oncol. 1990 Jul;8(7):1239-45. link to original article PubMed
  2. Rodenhuis S, Richel DJ, van der Wall E, Schornagel JH, Baars JW, Koning CC, Peterse JL, Borger JH, Nooijen WJ, Bakx R, Dalesio O, Rutgers E. Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet. 1998 Aug 15;352(9127):515-21. link to original article PubMed
  3. SBG 9401: Bergh J, Wiklund T, Erikstein B, Lidbrink E, Lindman H, Malmström P, Kellokumpu-Lehtinen P, Bengtsson NO, Söderlund G, Anker G, Wist E, Ottosson S, Salminen E, Ljungman P, Holte H, Nilsson J, Blomqvist C, Wilking N; Scandinavian Breast Group 9401 study. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Lancet. 2000 Oct 21;356(9239):1384-91. Erratum in: Lancet 2000 Dec 23-30;356(9248):2196. link to SD article PubMed
  4. Rodenhuis S, Bontenbal M, Beex LV, Wagstaff J, Richel DJ, Nooij MA, Voest EE, Hupperets P, van Tinteren H, Peterse HL, TenVergert EM, de Vries EG; Netherlands Working Party on Autologous Transplantation in Solid Tumors. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med. 2003 Jul 3;349(1):7-16. link to original article PubMed

Cyclophosphamide monotherapy

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Rubens et al. 1975 Phase III (C) CMFV Seems not superior

Chemotherapy

References

  1. Rubens RD, Knight RK, Hayward JL. Chemotherapy of advanced breast cancer: a controlled randomized trial of cyclophosphamide versus a four-drug combination. Br J Cancer. 1975 Dec;32(6):730-6. link to original article PubMed
  2. DBCG 77B: Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. link to original article contains verified protocol PubMed
    1. 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. link to original article PubMed

ECT, then auto HSCT

back to top

ECT: Epirubicin, Cyclophosphamide, Thiotepa

Regimen

Study Evidence Comparator Comparative Efficacy
Nitz et al. 2005 (WSG AM-01) Phase III (E-esc) ddEC x 4, then ddCMF x 3 Seems to have superior OS

No longer used, but of historical interest.

Preceding treatment

Chemotherapy

References

  1. WSG AM-01: Nitz UA, Mohrmann S, Fischer J, Lindemann W, Berdel WE, Jackisch C, Werner C, Ziske C, Kirchner H, Metzner B, Souchon R, Ruffert U, Schütt G, Pollmanns A, Schmoll HJ, Middecke C, Baltzer J, Schrader I, Wiebringhaus H, Ko Y, Rösel S, Schwenzer T, Wernet P, Hinke A, Bender HG, Frick M; West German Study Group. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial. Lancet. 2005 Dec 3;366(9501):1935-44. Erratum in: Lancet. 2006 Mar 4;367(9512):730. link to original article PubMed

FAC & BCG

back to top

FAC & BCG: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, BCG

Regimen

Study Evidence
Buzdar et al. 1979 Non-randomized

Preceding treatment

Chemotherapy

Immunotherapy

References

  1. Buzdar AU, Blumenschein GR, Gutterman JU, Tashima CK, Hortobagyi GN, Smith TL, Campos LT, Wheeler WL, Hersh EM, Freireich EJ, Gehan EA. Postoperative adjuvant chemotherapy with fluorouracil, doxorubicin, cyclophosphamide, and BCG vaccine: a follow-up report. JAMA. 1979 Oct 5;242(14):1509-13. link to original article PubMed

FNC

back to top

FNC: Fluorouracil, Novantrone (Mitoxantrone), Cyclophosphamide
CNF: Cyclophosphamide, Novantrone (Mitoxantrone), Fluorouracil

Regimen

Study Evidence Comparator Comparative Efficacy
Ron et al. 2001 Phase III (E-switch-ic) CMF Seems to have superior DFS
Fountzilas et al. 2004 (HE 10/92) Phase III (C) Tamoxifen Seems not superior
Toledano et al. 2007 (ARCOSEIN) Phase III (C) FNC & RT Seems not superior

Preceding treatment

Chemotherapy

21-day cycle for 6 cycles

Subsequent treatment

  • ARCOSEIN: RT

References

  1. Ron IG, Wigler N, Borovik R, Brufman G, Rizel S, Shani A, Brenner J, Farbstein H, Dale A, Inbar MJ, Brenner HJ, Chaitchik S, Catane R. CMF (cyclophosphamide, methotrexate, 5-fluorouracil) versus CNF (cyclophosphamide, mitoxantrone, 5-fluorouracil) as adjuvant chemotherapy for stage II lymph-node positive breast cancer: a phase III randomized multicenter study. Am J Clin Oncol. 2001 Aug;24(4):323-7. link to original article PubMed
  2. HE 10/92: Fountzilas G, Stathopoulos G, Kouvatseas G, Polychronis A, Klouvas G, Samantas E, Zamboglou N, Kyriakou K, Adamou A, Pectasidis D, Ekonomopoulos T, Kalofonos HP, Bafaloukos D, Georgoulias V, Razis E, Koukouras D, Zombolas V, Kosmidis P, Skarlos D, Pavlidis N; Hellenic Cooperative Oncology Group. Adjuvant cytotoxic and endocrine therapy in pre- and postmenopausal patients with breast cancer and one to nine infiltrated nodes: five-year results of the Hellenic Cooperative Oncology Group randomized HE 10/92 study. Am J Clin Oncol. 2004 Feb;27(1):57-67. link to original article PubMed
  3. ARCOSEIN: Toledano A, Azria D, Garaud P, Fourquet A, Serin D, Bosset JF, Miny-Buffet J, Favre A, Le Floch O, Calais G. Phase III trial of concurrent or sequential adjuvant chemoradiotherapy after conservative surgery for early-stage breast cancer: final results of the ARCOSEIN trial. J Clin Oncol. 2007 Feb 1;25(4):405-10. Erratum in: J Clin Oncol. 2007 Jun 1;25(16):2334. link to original article PubMed

Levamisole monotherapy

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Rojas et al. 1976 Randomized (E-esc) Observation Seems to have superior OS
Brincker et al. 1980 Randomized (E-switch-ooc) RT Seems to have inferior RFS

Note: Rojas et al. 1976 included patients with inoperable breast cancer; definitive therapy was RT.

Preceding treatment

  • Rojas et al. 1976: Radiotherapy
  • Brincker et al. 1980: Surgery

Immunotherapy

References

  1. Rojas AF, Feierstein JN, Mickiewicz E, Glait H, Olivari AJ. Levamisole in advanced human breast cancer. Lancet. 1976 Jan 31;1(7953):211-5. link to original article PubMed
  2. Brincker H, Mouridsen HT, Andersen KW, Andersen J, Castberg T, Fischermann K, Henriksen E, Hou-Jensen C, Johansen H, Rossing N, Rorth M; Executive Committee of the Danish Breast Cancer Cooperative Group. Increased breast-cancer recurrence rate after adjuvant therapy with levamisole: a preliminary report. Lancet. 1980 Oct 18;2(8199):824-7. link to original article PubMed

Melphalan monotherapy

back to top

P: Phenylalanine mustard (Melphalan)

Regimen

Study Evidence Comparator Comparative Efficacy
Fisher et al. 1975 (NSABP B-05) Phase III (E-esc) Placebo Might have superior DFS (*)
Fisher et al. 1977 (NSABP B-07) Phase III (C) PF Seems to have inferior RFS
Rubens et al. 1983 Phase III (E-esc) Observation Might have superior RFS

Note: Fisher et al. 1977 is an update for NSABP B-05 and also the primary results for NSABP B-07. Efficacy for NSABP B-05 is based on the 1986 update.

Preceding treatment

Chemotherapy

References

  1. NSABP B-05: Fisher B, Carbone P, Economou SG, Frelick R, Glass A, Lerner H, Redmond C, Zelen M, Band P, Katrych DL, Wolmark N, Fisher ER. 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer: a report of early findings. N Engl J Med. 1975 Jan 16;292(3):117-22. link to original article PubMed
    1. Update: Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. link to original article PubMed
    2. Update: Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986 Jun;4(6):929-41. link to original article PubMed
  2. NSABP B-07: Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. link to original article PubMed
  3. Rubens RD, Hayward JL, Knight RK, Bulbrook RD, Fentiman IS, Chaudary M, Howell A, Bush H, Crowther D, Sellwood RA, George WD, Howat JM. Controlled trial of adjuvant chemotherapy with melphalan for breast cancer. Lancet. 1983 Apr 16;1(8329):839-43. link to original article PubMed

MF

back to top

MF: Methotrexate & 5-Fluorouracil

Regimen

Study Evidence Comparator Comparative Efficacy
Fisher et al. 1989 (NSABP B-13) Phase III (E-esc) Observation Superior DFS (*)
Shapiro et al. 1993 Phase III (C) CMF Seems not superior
Fisher et al. 1996 (NSABP B-19) Phase III (C) CMF Might have inferior OS

Note: Reported efficacy for NSABP B-13 is based on the 1996 update.

Preceding treatment

Chemotherapy

References

  1. NSABP B-13: Fisher B, Redmond C, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, Glass A, Foster R, Caplan R. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med. 1989 Feb 23;320(8):473-8. link to original article PubMed
    1. Update: Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. link to original article PubMed
    2. Pooled update: Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. link to original article PubMed
  2. Shapiro CL, Gelman RS, Hayes DF, Osteen R, Obando A, Canellos GP, Frei E 3rd, Henderson IC. Comparison of adjuvant chemotherapy with methotrexate and fluorouracil with and without cyclophosphamide in breast cancer patients with one to three positive axillary lymph nodes. J Natl Cancer Inst. 1993 May 19;85(10):812-7. link to original article PubMed
  3. NSABP B-19: Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. link to original article PubMed
    1. Pooled update: Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. link to original article PubMed

MV

back to top

MV: Methotrexate & Vinblastine

Regimen

Study Evidence Comparator Comparative Efficacy
Assikis et al. 2003 Phase III (E-switch-ooc) See link 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

Chemotherapy

Supportive medications

21- to 28-day cycle for 4 cycles

References

  1. 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. link to original article contains protocol PubMed

Observation

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Bonadonna et al. 1976 Phase III (C) CMF Inferior RFS
Lacour et al. 1980 Phase III (C) Polya.Polyu Might have inferior OS
Brinker et al. 1983 (DBCG 77B) Phase III (C) 1. CMF Seems to have inferior OS (*)
2. Cyclophosphamide Seems to have inferior OS (*)
3. Levamisole Seems not superior
Goldhirsch et al. 1984 (LBCS III) Phase III (C) 1. CMFPT Inferior DFS
2. PT Inferior DFS
Goldhirsch et al. 1984 (LBCS IV) Phase III (C) PT Seems to have inferior DFS
Fisher et al. 1989 (NSABP B-13) Phase III (C) Sequential MF Inferior DFS (*)
Mansour et al. 1989 (INT-0011) Phase III (C) CMFP Inferior DFS
Paradiso et al. 2001 Phase III (C) FEC Seems to have inferior DFS
Henderson et al. 2003 (INT 0148/CALGB 9344) Phase III (C) Paclitaxel q3wk Inferior OS
Mamounas et al. 2005 (NSABP B-28) Phase III (C) Paclitaxel q3wk Inferior DFS

No further systemic treatment; many of these trials incorporated RT, however (see individual papers for details). Reported efficacy for DBCG 77B is based on the 2010 update. Reported efficacy for NSABP B-13 is based on the 1996 update.

Preceding treatment

References

  1. 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. link to original article PubMed
    1. 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. link to original article PubMed
    2. 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. PubMed
    3. 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. link to original article PubMed
  2. Lacour J, Lacour F, Spira A, Michelson M, Petit JY, Delage G, Sarrazin D, Contesso G, Viguier J. Adjuvant treatment with polyadenylic-polyuridylic acid (Polya-Polyu) in operable breast cancer. Lancet. 1980 Jul 26;2(8187):161-4. link to original article PubMed
  3. DBCG 77B: Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. link to original article contains verified protocol PubMed
    1. 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. link to original article PubMed
  4. LBCS III/IV: Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. link to original article PubMed
  5. NSABP B-13: Fisher B, Redmond C, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, Glass A, Foster R, Caplan R. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med. 1989 Feb 23;320(8):473-8. link to original article PubMed
    1. Update: Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. link to original article PubMed
    2. Pooled update: Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. link to original article PubMed
  6. INT-0011: Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med. 1989 Feb 23;320(8):485-90. link to original article PubMed
  7. LCBS V: Goldhirsch A, Gelber RD; Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med. 1989 Feb 23;320(8):491-6. link to original article PubMed
  8. Paradiso A, Schittulli F, Cellamare G, Mangia A, Marzullo F, Lorusso V, De Lena M. Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer. J Clin Oncol. 2001 Oct 1;19(19):3929-37. link to original article contains verified protocol PubMed
  9. INT 0148/CALGB 9344: Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. link to original article contains verified protocol PubMed
  10. NSABP B-28: Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. link to original article PubMed

Oophorectomy

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Ahmann et al. 1977 Phase III (C) CFP & Oophorectomy Seems to have inferior PFS

Preceding treatment

Hormonotherapy

References

  1. Ahmann DL, O'Connell MJ, Hahn RG, Bisel HF, Lee RA, Edmonson JH. An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advanced breast cancer undergoing oophorectomy. N Engl J Med. 1977 Aug 18;297(7):356-60. link to original article PubMed

Paclitaxel monotherapy, q3wk

back to top

T: Taxol (Paclitaxel)
P: Paclitaxel
pT: pacliTaxel

Variant #1, 175 mg/m2 q3wk

Study Evidence Comparator Comparative Efficacy
Henderson et al. 2003 (INT 0148/CALGB 9344) Phase III (E-RT-esc) Observation Superior OS
Romond et al. 2005 (NSABP B-31) Phase III (C) TH Inferior OS
Sparano et al. 2008 (ECOG E1199) Phase III (C) 1. Weekly Paclitaxel Inferior OS
2. Docetaxel q3wk Seems to have inferior DFS
3. Docetaxel weekly Seems not superior
Del Mastro et al. 2015 (GIM2) Phase III (C) See link See link
Earl et al. 2017 (tAnGo) Phase III (C) TG 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: Surgery, then AC x 4 versus high-dose AC x 4 versus very-high-dose AC x 4
  • NSABP B-31, and ECOG E1199: Surgery, then AC x 4
  • GIM2: Surgery, then EC x 4 versus FEC x 4
  • tAnGo: Surgery, then EC x 4

Chemotherapy

21-day cycle for 4 cycles

Variant #2, 225 mg/m2 q3wk

Study Evidence Comparator Comparative Efficacy
Mamounas et al. 2005 (NSABP B-28) Phase III (E-esc) Observation 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

Chemotherapy

21-day cycle for 4 cycles

References

  1. INT 0148/CALGB 9344: Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. link to original article contains verified protocol PubMed
  2. NSABP B-28: Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. link to original article PubMed
  3. NSABP B-31/NCCTG N9831: 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. link to original article PubMed
    1. Update: Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011 Sep 1;29(25):3366-73. Epub 2011 Jul 18. link to original article link to PMC article PubMed
    2. 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. link to original article link to PMC article PubMed
    3. 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. link to original article link to PMC article PubMed
    4. Update and HRQoL analysis: Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE Jr, Swain SM, Jeong JH, Fehrenbacher L, Gross HM, Brufsky AM, Flynn PJ, Wahl TA, Seay TE, Wade JL 3rd, Biggs DD, Atkins JN, Polikoff J, Zapas JL, Mamounas EP, Wolmark N. Long-term follow-up of cardiac function and quality of life for patients in NSABP protocol B-31/NRG Oncology: a randomized trial comparing the safety and efficacy of doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel and trastuzumab in patients with node-positive breast cancer with tumors overexpressing human epidermal growth factor receptor 2. J Clin Oncol. 2017 Dec 10;35(35):3942-3948. Epub 2017 Oct 26. link to original article link to PMC article PubMed
  4. ECOG E1199: Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. link to original article link to PMC article PubMed
    1. 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. link to original article link to PMC article PubMed
  5. GIM2: Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella (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. link to original article contains verified protocol PubMed
  6. tAnGo: Earl HM, Hiller L, Howard HC, Dunn JA, Young J, Bowden SJ, McDermaid M, Waterhouse AK, Wilson G, Agrawal R, O'Reilly S, Bowman A, Ritchie DM, Goodman A, Hickish T, McAdam K, Cameron D, Dodwell D, Rea DW, Caldas C, Provenzano E, Abraham JE, Canney P, Crown JP, Kennedy MJ, Coleman R, Leonard RC, Carmichael JA, Wardley AM, Poole CJ; tAnGo trial collaborators. Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):755-769. Epub 2017 May 4. link to original article contains protocol PubMed

PAF

back to top

PAF: Phenylalanine mustard (Melphalan), Adriamycin (Doxorubicin), Fluorouracil

Regimen

Study Evidence Comparator Comparative Efficacy
Fisher et al. 1989 (NSABP B-11) Phase III (E-esc) PF Seems to have superior OS

Preceding treatment

Chemotherapy

References

  1. NSABP B-11: Fisher B, Redmond C, Wickerham DL, Bowman D, Schipper H, Wolmark N, Sass R, Fisher ER, Jochimsen P, Legault-Poisson S, Dimitrov N, Wolter J, Bornstein R, Elias EG, LiCalzi N, Paterson AHG, Sutherland CM. Doxorubicin-containing regimens for the treatment of stage II breast cancer: the National Surgical Adjuvant Breast and Bowel Project experience. J Clin Oncol. 1989 May;7(5):572-82. link to original article PubMed

PF

back to top

PF: Phenylalanine mustard (Melphalan) & Fluorouracil

Regimen

Study Evidence Comparator Comparative Efficacy
Fisher et al. 1977 (NSABP B-07) Phase III (E-esc) P Seems to have superior RFS
Fisher et al. 1980 (NSABP B-08) Phase III (C) PFM Seems not superior
Fisher et al. 1981 (NSABP B-09) Phase III (C) PFT Inferior RFS
Fisher et al. 1989 (NSABP B-11) Phase III (C) PAF Seems to have inferior OS
Fisher et al. 1990 (NSABP B-10) Phase III (C) PFCp Seems not superior

Note: Fisher et al. 1980 is more of a meta-analysis than a primary publication, but is to our knowledge the first manuscript to report the findings from NSABP B-08, which was a negative trial.

Preceding treatment

Chemotherapy

References

  1. NSABP B-07: Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. link to original article PubMed
  2. NSABP B-08: Fisher B, Redmond C, Fisher ER. The contribution of recent NSABP clinical trials of primary breast cancer therapy to an understanding of tumor biology--an overview of findings. Cancer. 1980 Aug 15;46(4 Suppl):1009-25. link to original article PubMed
  3. NSABP B-09: Fisher B, Redmond C, Brown A, Wolmark N, Wittliff J, Fisher ER, Plotkin D, Bowman D, Sachs S, Wolter J, Frelick R, Desser R, LiCalzi N, Geggie P, Campbell T, Elias EG, Prager D, Koontz P, Volk H, Dimitrov N, Gardner B, Lerner H, Shibata H. Treatment of primary breast cancer with chemotherapy and tamoxifen. N Engl J Med. 1981 Jul 2;305(1):1-6. link to original article PubMed
    1. Update: Fisher B, Redmond C, Brown A, Fisher ER, Wolmark N, Bowman D, Plotkin D, Wolter J, Bornstein R, Legault-Poisson S, Saffer EA. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial. J Clin Oncol. 1986 Apr;4(4):459-71. link to original article PubMed
    2. Update: Fisher B, Brown A, Wolmark N, Redmond C, Wickerham DL, Wittliff J, Dimitrov N, Legault-Poisson S, Schipper H, Prager D. Prolonging tamoxifen therapy for primary breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial. Ann Intern Med. 1987 May;106(5):649-54. link to original article PubMed
  4. NSABP B-11: Fisher B, Redmond C, Wickerham DL, Bowman D, Schipper H, Wolmark N, Sass R, Fisher ER, Jochimsen P, Legault-Poisson S, Dimitrov N, Wolter J, Bornstein R, Elias EG, LiCalzi N, Paterson AHG, Sutherland CM. Doxorubicin-containing regimens for the treatment of stage II breast cancer: the National Surgical Adjuvant Breast and Bowel Project experience. J Clin Oncol. 1989 May;7(5):572-82. link to original article PubMed
  5. NSABP B-10: Fisher B, Brown A, Wolmark N, Fisher ER, Redmond C, Wickerham DL, Margolese R, Dimitrov N, Pilch Y, Glass A, Sutherland C, Foster R. Evaluation of the worth of corynebacterium parvum in conjunction with chemotherapy as adjuvant treatment for primary breast cancer: eight-year results from the National Surgical Adjuvant Breast and Bowel Project B-10. Cancer. 1990 Jul 15;66(2):220-7. link to original article PubMed

PFT

back to top

PFT: Phenylalanine mustard (Melphalan), 5-Fluorouracil, Tamoxifen

Regimen

Study Evidence Comparator Comparative Efficacy
Fisher et al. 1981 (NSABP B-09) Phase III (E-RT-esc) PF Superior RFS
Fisher et al. 1990 (NSABP B-16) Phase III (E-esc) 1. ACT Not reported
2. Tamoxifen Seems to have superior DDFS

Preceding treatment

Chemotherapy

Hormonotherapy

References

  1. NSABP B-09: Fisher B, Redmond C, Brown A, Wolmark N, Wittliff J, Fisher ER, Plotkin D, Bowman D, Sachs S, Wolter J, Frelick R, Desser R, LiCalzi N, Geggie P, Campbell T, Elias EG, Prager D, Koontz P, Volk H, Dimitrov N, Gardner B, Lerner H, Shibata H. Treatment of primary breast cancer with chemotherapy and tamoxifen. N Engl J Med. 1981 Jul 2;305(1):1-6. link to original article PubMed
    1. Update: Fisher B, Redmond C, Brown A, Fisher ER, Wolmark N, Bowman D, Plotkin D, Wolter J, Bornstein R, Legault-Poisson S, Saffer EA. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial. J Clin Oncol. 1986 Apr;4(4):459-71. link to original article PubMed
    2. Update: Fisher B, Brown A, Wolmark N, Redmond C, Wickerham DL, Wittliff J, Dimitrov N, Legault-Poisson S, Schipper H, Prager D. Prolonging tamoxifen therapy for primary breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial. Ann Intern Med. 1987 May;106(5):649-54. link to original article PubMed
  2. NSABP B-16: Fisher B, Redmond C, Legault-Poisson S, Dimitrov NV, Brown AM, Wickerham DL, Wolmark N, Margolese RG, Bowman D, Glass AG, Kardinal CG, Robidoux A, Jochimsen P, Cronin W, Deutsch M, Fisher ER, Myers DB, Hoehn JL. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990 Jun;8(6):1005-18. link to original article PubMed
    1. Pooled update: Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. link to original article PubMed

Placebo

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Fisher et al. 1975 (NSABP B-05) Phase III (C) Melphalan Might have inferior DFS (*)

No active antineoplastic treatment after mastectomy. Used as a comparator arm, historically. Reported efficacy for NSABP B-05 is based on the 1986 update.

Preceding treatment

References

  1. NSABP B-05: Fisher B, Carbone P, Economou SG, Frelick R, Glass A, Lerner H, Redmond C, Zelen M, Band P, Katrych DL, Wolmark N, Fisher ER. 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer: a report of early findings. N Engl J Med. 1975 Jan 16;292(3):117-22. link to original article PubMed
    1. Update: Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. link to original article PubMed
    2. Update: Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986 Jun;4(6):929-41. link to original article PubMed

PT

back to top

PT: Prednisone & Tamoxifen

Regimen

Study Evidence Comparator Comparative Efficacy
Goldhirsch et al. 1984 (LBCS III) Phase III (E-esc) 1. CMFPT Seems to have inferior DFS
2. Observation Superior DFS
Goldhirsch et al. 1984 (LBCS IV) Phase III (E-esc) Observation Seems to have superior DFS

Preceding treatment

Hormonotherapy

References

  1. LBCS III/IV: Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. link to original article PubMed

TMF

back to top

TMF: Thiotepa, Methotrexate, Fluorouracil

Regimen

Study Evidence
Semiglazov et al. 1994 Non-randomized portion of RCT

Preceding treatment

Chemotherapy

References

  1. Semiglazov VF, Topuzov EE, Bavli JL, Moiseyenko VM, Ivanova OA, Seleznev IK, Orlov AA, Barash NY, Golubeva OM, Chepic OF. Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer. Ann Oncol. 1994 Sep;5(7):591-5. link to original article PubMed

Metastatic disease, all lines of therapy

Aminoglutethimide monotherapy

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Smith et al. 1978 Non-randomized
Santen et al. 1981 Phase III (E-switch-ic) Bilateral adrenalectomy Did not meet primary endpoint of ORR
Stuart-Harris et al. 1984 Phase II
Canney et al. 1988 Phase III (E-switch-ic) MPA Did not meet primary endpoint of ORR
Lundgren et al. 1989 Phase III (E-switch-ic) Megestrol Did not meet primary endpoint of ORR
Garcia-Giralt et al. 1992 Phase III (E-switch-ic) MPA Seems to have superior TTP
Robustelli della Cuna et al. 1993 Phase III (C) Aminoglutethimide; higher-dose Did not meet primary endpoint of ORR
Gale et al. 1994 Phase III (E-switch-ic) 1. Tamoxifen
2. Bilateral adrenalectomy 		Did not meet primary endpoints of DOR/TTF/OS

Hormonotherapy

Supportive medications

References

  1. Smith IE, Fitzharris BM, McKinna JA, Fahmy DR, Nash AG, Neville AM, Gazet JC, Ford HT, Powles TJ. Aminoglutethimide in treatment of metastatic breast carcinoma. Lancet. 1978 Sep 23;2(8091):646-9. link to original article PubMed
  2. Santen RJ, Worgul TJ, Samojlik E, Interrante A, Boucher AE, Lipton A, Harvey HA, White DS, Smart E, Cox C, Wells SA. A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer. N Engl J Med. 1981 Sep 3;305(10):545-51. link to original article PubMed
  3. Stuart-Harris R, Dowsett M, Bozek T, McKinna JA, Gazet JC, Jeffcoate SL, Kurkure A, Carr L, Smith IE. Low-dose aminoglutethimide in treatment of advanced breast cancer. Lancet. 1984 Sep 15;2(8403):604-7. link to original article PubMed
  4. Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, Spooner D. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. J Natl Cancer Inst. 1988 Sep 21;80(14):1147-51. link to original article PubMed
  5. Lundgren S, Gundersen S, Klepp R, Lønning PE, Lund E, Kvinnsland S. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Res Treat. 1989 Nov;14(2):201-6. link to original article PubMed
  6. Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P, Fumoleau P, Gorins A, Guerin D, Guerin R, Maillart P, Mauriac L, May-Levin F, Metz R, Namer M, Olivier JP, Pommatau E, Pouillart P, Pujade-Lauraine E, Rouesse J, Serrou B, Vitse M, Zylberait D. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Res Treat. 1992;24(2):139-45. link to original article PubMed
  7. Robustelli della Cuna G, Pannuti F, Martoni A, Camaggi CM, Strocchi E, Da Prada GA, Tanneberger S; Italian Cooperative Group. Aminoglutethimide in advanced breast cancer: prospective, randomized comparison of two dose levels. Anticancer Res. 1993 Nov-Dec;13(6B):2367-71. PubMed
  8. Gale KE, Andersen JW, Tormey DC, Mansour EG, Davis TE, Horton J, Wolter JM, Smith TJ, Cummings FJ. Hormonal treatment for metastatic breast cancer: an Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen. Cancer. 1994 Jan 15;73(2):354-61. link to original article PubMed

CAMF

back to top

CAMF: Cyclophosphamide, Adriamycin (Doxorubicin), Methotrexate, Fluorouracil
AFCM: Adriamycin (Doxorubicin), Fluorouracil, Cyclophosphamide, Methotrexate

Regimen

Study Evidence Comparator Comparative Efficacy
Tranum et al. 1978 Randomized (E-esc) 1. AF
2. FAC 		Did not meet primary endpoint of ORR
Bezwoda et al. 1979 Randomized (E-switch-ic) CMFV Did not meet primary endpoint of ORR
Lippman et al. 1984 Randomized (C) CAMFTP Seems not superior

Chemotherapy

References

  1. Tranum B, Hoogstraten B, Kennedy A, Vaughn CB, Samal B, Thigpen T, Rivkin S, Smith F, Palmer RL, Costanzi J, Tucker WG, Wilson H, Maloney TR. Adriamycin in combination for the treatment of breast cancer: a Southwest Oncology Group study. Cancer. 1978 Jun;41(6):2078-83. link to original article PubMed
  2. Bezwoda WR, de Moor NG, Derman D, Lange M, Saner R, Dando R. Combination chemotherapy of metastatic breast cancer: a randomized trial comparing the use of adriamycin to that of Vinblastine. Cancer. 1979 Aug;44(2):392-7. link to original article PubMed
  3. Lippman ME, Cassidy J, Wesley M, Young RC. A randomized attempt to increase the efficacy of cytotoxic chemotherapy in metastatic breast cancer by hormonal synchronization. J Clin Oncol. 1984 Jan;2(1):28-36. link to original article PubMed

CAF & MPA

back to top

CAF & MPA: Cyclophosphamide, Adriamycin (Doxorubicin), Fluorouracil, MedroxyProgesterone Acetate

Regimen

Study Evidence Comparator Comparative Efficacy
Tominaga et al. 1994 Phase III (E-esc) CAF Seems to have superior ORR

Chemotherapy

Hormonotherapy

References

  1. Tominaga T, Abe O, Ohshima A, Hayasaka H, Uchino J, Abe R, Enomoto K, Izuo M, Watanabe H, Takatani O, Yoshida M, Sakai K, Koyama H, Hattori T, Senoo T, Monden Y, Nomura Y. Comparison of chemotherapy with or without medroxyprogesterone acetate for advanced or recurrent breast cancer. Eur J Cancer. 1994;30A(7):959-64. link to original article contains protocol PubMed

CAFVP

back to top

CAFVP: Cyclophosphamide, Adriamycin (Doxorubicin), Fluorouracil, Vincristine, Prednisone

Regimen

Study Evidence Comparator Comparative Efficacy
Muss et al. 1978 Phase III (E-switch-ic) CMFVP Might have superior OS
Aisner et al. 1987 Phase III (E-esc) 1. CAF Not reported
2. CMF Superior ORR

Chemotherapy

Hormonotherapy

References

  1. Muss HB, White DR, Richards F 2nd, Cooper MR, Stuart JJ, Jackson DV, Rhyne L, Spurr CL. Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial. Cancer. 1978 Nov;42(5):2141-8. link to original article PubMed
  2. Aisner J, Weinberg V, Perloff M, Weiss R, Perry M, Korzun A, Ginsberg S, Holland JF; Cancer and Leukemia Group B. Chemotherapy versus chemoimmunotherapy (CAF v CAFVP v CMF each +/- MER) for metastatic carcinoma of the breast: a CALGB study. J Clin Oncol. 1987 Oct;5(10):1523-33. link to original article contains protocol PubMed

CFP

back to top

CFP: Cyclophosphamide, Fluorouracil, Prednisone

Regimen

Study Evidence Comparator Comparative Efficacy
Creagan et al. 1984 Phase III (C) CAP, then CFP Did not meet primary endpoint of ORR
Rosner et al. 1987 Phase III (E-esc) 1. CA
2. CMFVP 		Did not meet primary endpoint of OS
Marschke et al. 1989 Phase III (C) CMFP Might have inferior ORR

Chemotherapy

Hormonotherapy

References

  1. Creagan ET, Green SJ, Ahmann DL, Ingle JN, Edmonson JH, Marschke RF Jr. A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer. J Clin Oncol. 1984 Nov;2(11):1260-5. link to original article PubMed
  2. Rosner D, Nemoto T, Lane WW. A randomized study of intensive versus moderate chemotherapy programs in metastatic breast cancer. Cancer. 1987 Mar 1;59(5):874-83. link to original article PubMed
  3. Marschke RF Jr, Ingle JN, Schaid DJ, Krook JE, Mailliard JA, Cullinan SA, Pfeifle DM, Votava HJ, Ebbert LP, Windschitl HE. Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer. Cancer. 1989 May 15;63(10):1931-7. link to original article PubMed

Chlorambucil & Prednisolone

back to top

Regimen

Study Evidence
Freckman et al. 1964 Non-randomized

Chemotherapy

Hormonotherapy

References

  1. Freckman HA, Fry HL, Mendez FL, Maurer ER. Chlorambucil-prednisolone therapy for disseminated breast carcinoma. JAMA. 1964 Jul 6;189:23-6. link to original article PubMed

CHUT, then auto HSCT

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Biron et al. 2007 (Pegase 03) Phase III (E-esc) No further treatment Superior DFS

Preceding treatment

Chemotherapy

References

  1. Pegase 03: Biron P, Durand M, Roché H, Delozier T, Battista C, Fargeot P, Spaeth D, Bachelot T, Poiget E, Monnot F, Tanguy ML, Curé H. Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer. Bone Marrow Transplant. 2008 Mar;41(6):555-62. Epub 2007 Nov 26. link to original article PubMed

CMFP

back to top

CMFP: Cyclophosphamide, Methotrexate, Fluorouracil, Prednisone

Regimen

Study Evidence Comparator Comparative Efficacy
Canellos et al. 1974 Non-randomized
Tormey et al. 1982 (ECOG E2173) Phase III (E-esc) 1. AV
2. CMF 		Seems to have superior OS
Segaloff et al. 1985 Phase III (C) CMFVP Did not meet primary endpoint of OS
Cummings et al. 1985 Phase III (E-esc) CAF Did not meet primary endpoint of ORR
Marschke et al. 1989 Phase III (E-esc) CFP Might have superior ORR
Bishop et al. 1999 Phase III (C) Paclitaxel Seems to have inferior OS

Chemotherapy

Hormonotherapy

References

  1. Canellos GP, Devita VT, Gold GL, Chabner BA, Schein PS, Young RC. Cyclical combination chemotherapy for advanced breast carcinoma. Br Med J. 1974 Feb 9;1(5901):218-20. link to original article PubMed
  2. ECOG E2173: Tormey DC, Gelman R, Band PR, Sears M, Rosenthal SN, DeWys W, Perlia C, Rice MA. Comparison of induction chemotherapies for metastatic breast cancer: an Eastern Cooperative Oncology Group Trial. Cancer. 1982 Oct 1;50(7):1235-44. link to original article PubMed
  3. Segaloff A, Hankey BF, Carter AC, Escher GC, Ansfield FJ, Talley RW. An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone in advanced breast cancer. Breast Cancer Res Treat. 1985;5(3):311-9. link to original article PubMed
  4. Cummings FJ, Gelman R, Horton J. Comparison of CAF versus CMFP in metastatic breast cancer: analysis of prognostic factors. J Clin Oncol. 1985 Jul;3(7):932-40. link to original article PubMed
  5. Marschke RF Jr, Ingle JN, Schaid DJ, Krook JE, Mailliard JA, Cullinan SA, Pfeifle DM, Votava HJ, Ebbert LP, Windschitl HE. Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer. Cancer. 1989 May 15;63(10):1931-7. link to original article PubMed
  6. Bishop JF, Dewar J, Toner GC, Smith J, Tattersall MH, Olver IN, Ackland S, Kennedy I, Goldstein D, Gurney H, Walpole E, Levi J, Stephenson J, Canetta R. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2355-64. link to original article contains protocol PubMed

CMFV

back to top

CMFV: Cyclophosphamide, Methotrexate, Fluorouracil, Vinblastine
CVMF: Cyclophosphamide, Vinblastine, Methotrexate, Fluorouracil

Regimen

Study Evidence Comparator Comparative Efficacy
Edelstyn et al. 1975 Randomized (E-esc) CMFV; 1-day Superior ORR
Bezwoda et al. 1979 Randomized (C) CAMF Did not meet primary endpoint of ORR

Chemotherapy

References

  1. Edelstyn GA, Bates TD, Brinkley D, MacRae KD, Spittle MF, Wheeler T. Comparison of 5-day, 1-day, and 2-day cyclical combination chemotherapy in advanced breast cancer. Lancet. 1975 Aug 2;2(7927):209-11. link to SD article PubMed
  2. Bezwoda WR, de Moor NG, Derman D, Lange M, Saner R, Dando R. Combination chemotherapy of metastatic breast cancer: a randomized trial comparing the use of adriamycin to that of Vinblastine. Cancer. 1979 Aug;44(2):392-7. link to original article PubMed

CMFVP

back to top

CMFVP: Cyclophosphamide, Methotrexate, Fluorouracil, Vincristine, Prednisone
COMFP: Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Fluorouracil, Prednisone
CFPMV: Cyclophosphamide, Fluorouracil, Prednisone, Methotrexate, Vincristine

Regimen

Study Evidence Comparator Comparative Efficacy
Smalley et al. 1977 Phase III (C) CAF Might have inferior OS (*)
Muss et al. 1978 Phase III (C) CAFVP Might have inferior OS
Segaloff et al. 1985 Phase III (E-esc) CMFP Did not meet primary endpoint of OS
Rosner et al. 1987 Phase III (E-esc) 1. CA
2. CFP 		Did not meet primary endpoint of OS

Note: reported efficacy for Smalley et al. 1977 is based on the 1983 update.

Chemotherapy

Hormonotherapy

References

  1. Smalley RV, Carpenter J, Bartolucci A, Vogel C, Krauss S. A comparison of cyclophosphamide, adriamycin, 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone (CMFVP) in patients with metastatic breast cancer: a Southeastern Cancer Study Group project. Cancer. 1977 Aug;40(2):625-32. link to original article contains verified protocol PubMed
    1. Update: Smalley RV, Lefante J, Bartolucci A, Carpenter J, Vogel C, Krauss S. A comparison of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) in patients with advanced breast cancer. Breast Cancer Res Treat. 1983;3(2):209-20. link to original article PubMed
  2. Muss HB, White DR, Richards F 2nd, Cooper MR, Stuart JJ, Jackson DV, Rhyne L, Spurr CL. Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial. Cancer. 1978 Nov;42(5):2141-8. link to original article PubMed
  3. Segaloff A, Hankey BF, Carter AC, Escher GC, Ansfield FJ, Talley RW. An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone in advanced breast cancer. Breast Cancer Res Treat. 1985;5(3):311-9. link to original article PubMed
  4. Rosner D, Nemoto T, Lane WW. A randomized study of intensive versus moderate chemotherapy programs in metastatic breast cancer. Cancer. 1987 Mar 1;59(5):874-83. link to original article PubMed

DES monotherapy

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Kennedy 1965 Randomized (E-switch-ic) Testosterone Not available
Carter et al. 1977 Phase III (E-switch-ic) DES; other dosings See paper
Ingle et al. 1981 Phase III (C) Tamoxifen Did not meet primary endpoint of ORR
Kiang et al. 1981 Phase III (C) Cyclophosphamide, 5-FU, DES Seems to have inferior OS (*)

No longer used, but of historical interest. Reported efficacy for Kiang et al. 1981 is based on the 1985 update.

Hormonotherapy

References

  1. Kennedy BJ. Diethylstilbestrol versus testosterone propionate therapy in advanced breast cancer. Surg Gynecol Obstet. 1965 Jun;120:1246-50. PubMed
  2. Carter AC, Sedransk N, Kelley RM, Ansfield FJ, Ravdin RG, Talley RW, Potter NR. Diethylstilbestrol: recommended dosages for different categories of breast cancer patients: report of the Cooperative Breast Cancer Group. JAMA. 1977 May 9;237(19):2079-8. link to original article PubMed
  3. Ingle JN, Ahmann DL, Green SJ, Edmonson JH, Bisel HF, Kvols LK, Nichols WC, Creagan ET, Hahn RG, Rubin J, Frytak S. Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N Engl J Med. 1981 Jan 1;304(1):16-21. link to original article PubMed
  4. Kiang DT, Frenning DH, Gay J, Goldman AI, Kennedy BJ. Combination therapy of hormone and cytotoxic agents in advanced breast cancer. Cancer. 1981 Feb 1;47(3):452-6. link to original article PubMed
    1. Update: Kiang DT, Gay J, Goldman A, Kennedy BJ. A randomized trial of chemotherapy and hormonal therapy in advanced breast cancer. N Engl J Med. 1985 Nov 14;313(20):1241-6. link to original article PubMed

CTCb, then auto HSCT

back to top

CTCb: Cyclophosphamide, Thiotepa, Carboplatin

Regimen

Study Evidence Comparator Comparative Efficacy
Stadtmauer et al. 2000 Phase III (E-esc) CMF Did not meet primary endpoint of OS

No longer used, but of historical interest.

Chemotherapy

References

  1. Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK, Sickles C, Glick JH; Philadelphia Bone Marrow Transplant Group. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med. 2000 Apr 13;342(15):1069-76. link to original article PubMed

Estradiol monotherapy

back to top

Variant #1, 6 mg/day

Study Evidence Comparator Comparative Efficacy
Ellis et al. 2009 Randomized Phase II (E-de-esc) Estradiol; 30 mg/day Did not meet primary endpoint of CBR

Hormonotherapy

Continued indefinitely

Variant #2, 30 mg/day

Study Evidence Comparator Comparative Efficacy
Ellis et al. 2009 Randomized Phase II (C) Estradiol; 6 mg/day Did not meet primary endpoint of CBR

Hormonotherapy

Continued indefinitely

References

  1. Ellis MJ, Gao F, Dehdashti F, Jeffe DB, Marcom PK, Carey LA, Dickler MN, Silverman P, Fleming GF, Kommareddy A, Jamalabadi-Majidi S, Crowder R, Siegel BA. Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study. JAMA. 2009 Aug 19;302(7):774-80. link to original article link to PMC article contains protocol PubMed

Fluoxymesterone monotherapy

back to top

Regimen

Study Evidence
Kennedy 1958 Non-randomized

Hormonotherapy

References

  1. Kennedy BJ. Fluoxymesterone therapy in advanced breast cancer. N Engl J Med. 1958 Oct 2;259(14):673-5. link to original article PubMed

Formestane monotherapy

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Coombes et al. 1984 Pilot
Thürlimann et al. 1997 (SAKK 20/90) Phase III (E-switch-ic) Megestrol Did not meet primary endpoint of TTF

Hormonotherapy

References

  1. Coombes RC, Goss P, Dowsett M, Gazet JC, Brodie A. 4-Hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. Lancet. 1984 Dec 1;2(8414):1237-9. link to original article PubMed
  2. SAKK 20/90: Thürlimann B, Castiglione M, Hsu-Schmitz SF, Cavalli F, Bonnefoi H, Fey MF, Morant R, Löhnert T, Goldhirsch A; Swiss Group for Clinical Cancer Research (SAKK). Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Eur J Cancer. 1997 Jun;33(7):1017-24. link to original article PubMed

Medroxyprogesterone monotherapy

back to top

Variant #1, 500 mg/day

Study Evidence Comparator Comparative Efficacy
Cuna et al. 1978 Phase III (E-de-esc) MPA; 1000 mg/day Did not meet primary endpoint of ORR
Pannuti et al. 1979 Phase III (C) MPA; 1500 mg/day Did not meet primary endpoint of ORR
Canney et al. 1988 Phase III (C) Aminoglutethimide Did not meet primary endpoint of ORR
Byrne et al. 1997 (ANZ8613) Phase III (C) MPA & Tamoxifen Did not meet primary endpoint of TTP

Note: Canney et al. 1988 does not have dosing information in the abstract.

Hormonotherapy

Continued indefinitely

Variant #2, 900 mg/day

Study Evidence Comparator Comparative Efficacy
van Veelen et al. 1986 Phase III (E-switch-ic) Tamoxifen Did not meet primary endpoint of ORR

Hormonotherapy

Continued indefinitely

Variant #3, 1000 mg/day (high-dose)

Study Evidence Comparator Comparative Efficacy
Cavalli et al. 1984 Phase III (E-esc) MPA; low-dose Superior ORR
Garcia-Giralt et al. 1992 Phase III (C) Aminoglutethimide Seems to have inferior TTP
Castiglione-Gertsch et al. 1993 Phase III (E-switch-ic) Tamoxifen Might have superior TTP
Muss et al. 1994 Phase III (E-switch-ic) Tamoxifen Might have superior OS

Hormonotherapy

Continued indefinitely

References

  1. Cuna GR, Calciati A, Strada MR, Bumma C, Campio L. High dose medroxyprogesterone acetate (MPA) treatment in metastatic carcinoma of the breast: a dose-response evaluation. Tumori. 1978 Apr 30;64(2):143-9. link to original article contains protocol PubMed
  2. Pannuti F, Martoni A, Di Marco AR, Piana E, Saccani F, Becchi G, Mattioli G, Barbanti F, Marra GA, Persiani W, Cacciari L, Spagnolo F, Palenzona D, Rocchetta G. Prospective, randomized clinical trial of two different high dosages of medroxyprogesterone acetate (MAP) in the treatment of metastatic breast cancer. Eur J Cancer. 1979 Apr;15(4):593-601. link to original article contains protocol PubMed
  3. Cavalli F, Goldhirsch A, Jungi F, Martz G, Mermillod B, Alberto P. Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer. J Clin Oncol. 1984 May;2(5):414-9. link to original article PubMed
  4. van Veelen H, Willemse PH, Tjabbes T, Schweitzer MJ, Sleijfer DT. Oral high-dose medroxyprogesterone acetate versus tamoxifen: a randomized crossover trial in postmenopausal patients with advanced breast cancer. Cancer. 1986 Jul 1;58(1):7-13. link to original article contains protocol PubMed
  5. Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, Spooner D. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. J Natl Cancer Inst. 1988 Sep 21;80(14):1147-51. link to original article PubMed
  6. Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P, Fumoleau P, Gorins A, Guerin D, Guerin R, Maillart P, Mauriac L, May-Levin F, Metz R, Namer M, Olivier JP, Pommatau E, Pouillart P, Pujade-Lauraine E, Rouesse J, Serrou B, Vitse M, Zylberait D. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Res Treat. 1992;24(2):139-45. link to original article PubMed
  7. Castiglione-Gertsch M, Pampallona S, Varini M, Cavalli F, Brunner K, Senn HJ, Goldhirsch A, Metzger U. Primary endocrine therapy for advanced breast cancer: to start with tamoxifen or with medroxyprogesterone acetate?. Ann Oncol. 1993 Nov;4(9):735-40. link to original article PubMed
  8. Muss HB, Case LD, Atkins JN, Bearden JD 3rd, Cooper MR, Cruz JM, Jackson DV Jr, O'Rourke MA, Pavy MD, Powell BL, Richards F, SPurr CL, Eagle K, White DR. Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study. J Clin Oncol. 1994 Aug;12(8):1630-8. link to original article contains protocol PubMed
  9. ANZ8613: Byrne MJ, Gebski V, Forbes J, Tattersall MH, Simes RJ, Coates AS, Dewar J, Lunn M, Flower C, Gill PG, Stewart J; Australian-New Zealand Breast Cancer Trials Group. Medroxyprogesterone acetate addition or substitution for tamoxifen in advanced tamoxifen-resistant breast cancer: a phase III randomized trial. J Clin Oncol. 1997 Sep;15(9):3141-8. link to original article contains protocol PubMed

Megestrol monotherapy

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Muss et al. 1988 Phase III (E-switch-ic) Tamoxifen Did not meet primary endpoint of ORR
Lundgren et al. 1989 Phase III (C) Aminoglutethimide Did not meet primary endpoint of ORR
Muss et al. 1990 Phase III (C) Megestrol; higher-dose Seems to have inferior OS
Gill et al. 1993 Phase III (E-switch-ic) 1. Tamoxifen
2. Megestrol & Tamoxifen 		Seems not superior
Jonat et al. 1996 Phase III (C) Anastrozole Seems to have inferior OS (*)
Buzdar et al. 1996 (Protocol 03) Phase III (C) Fadrozole Did not meet primary endpoint of ORR
Buzdar et al. 1996 (Protocol 06) Phase III (C) Fadrozole Did not meet primary endpoint of ORR
Buzdar et al. 1996a Phase III (C) Anastrozole Seems to have inferior OS (*)
Stuart et al. 1996 Phase III (E-switch-ic) Tamoxifen Seems not superior
Thürlimann et al. 1997 (SAKK 20/90) Phase III (C) Formestane Did not meet primary endpoint of TTF
Russell et al. 1997 (SWOG S8312) Phase III (C) Aminoglutethimide, Hydrocortisone, Megestrol Seems not superior
Dombernowsky et al. 1998 Randomized (C) Letrozole; 0.5 mg/day Not reported
Letrozole; 2.5 mg/day Seems to have inferior OS
Goss et al. 1999 Phase III (C) Vorozole Did not meet primary endpoint of ORR
Abrams et al. 1999 (CALGB 8741) Phase III (C) Megestrol; higher-dose Did not meet primary endpoint of ORR
Kaufmann et al. 2000 Phase III (C) Exemestane Seems to have inferior OS
Buzdar et al. 2001 Phase III (C) 1. Letrozole; 0.5 mg/day
2. Letrozole; 2.5 mg/day 		Did not meet primary endpoint of ORR

Note: Reported efficacy for Jonat et al. 1996 & Buzdar et al. 1996a is based on the 1998 pooled update.

Hormonotherapy

  • Megestrol (Megace) 160 mg PO once per day
    • Kaufmann et al. 2000 gave as 40 mg PO four times per day

Continued indefinitely

References

  1. Muss HB, Wells HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, Powell BL, Richards F, White DR, Zekan PJ, Spurr CL, Pope E, Case D, Morgan TM. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1988 Jul;6(7):1098-106. link to original article PubMed
  2. Lundgren S, Gundersen S, Klepp R, Lønning PE, Lund E, Kvinnsland S. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Res Treat. 1989 Nov;14(2):201-6. link to original article PubMed
  3. Muss HB, Case LD, Capizzi RL, Cooper MR, Cruz J, Jackson D, Richards F 2nd, Powell BL, Spurr CL, White D, Zekan P, Read S, Cates-Wilkie S, Bearden J, McCullough J, Callahan R, Karb K, Atkins J, Paschal B, Ramseur B, Lusk J, Stanley V. High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1990 Nov;8(11):1797-805. link to original article PubMed
  4. Gill PG, Gebski V, Snyder R, Burns I, Levi J, Byrne M, Coates A. Randomized comparison of the effects of tamoxifen, megestrol acetate, or tamoxifen plus megestrol acetate on treatment response and survival in patients with metastatic breast cancer. Ann Oncol. 1993 Nov;4(9):741-4. link to original article contains protocol PubMed
  5. Jonat W, Howell A, Blomqvist C, Eiermann W, Winblad G, Tyrrell C, Mauriac L, Roche H, Lundgren S, Hellmund R, Azab M. A randomised trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer. Eur J Cancer. 1996 Mar;32A(3):404-12. link to original article contains protocol PubMed
    1. Pooled update: Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. link to original article PubMed
    2. Pooled update: Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. link to original article PubMed
  6. Buzdar AU, Smith R, Vogel C, Bonomi P, Keller AM, Favis G, Mulagha M, Cooper J. Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: results of two randomized double blind controlled multiinstitutional trials. Cancer. 1996 Jun 15;77(12):2503-13. link to original article PubMed
  7. Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. link to original article PubMed
    1. Update: Buzdar AU, Jones SE, Vogel CL, Wolter J, Plourde P, Webster A; Arimidex Study Group. A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Cancer. 1997 Feb 15;79(4):730-9. link to original article contains protocol PubMed
    2. Pooled update: Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. link to original article PubMed
  8. Stuart NS, Warwick J, Blackledge GR, Spooner D, Keen C, Taylor AR, Tyrell C, Webster DJ, Earl H. A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer. Eur J Cancer. 1996 Oct;32A(11):1888-92. link to original article contains verified protocol PubMed
  9. SAKK 20/90: Thürlimann B, Castiglione M, Hsu-Schmitz SF, Cavalli F, Bonnefoi H, Fey MF, Morant R, Löhnert T, Goldhirsch A; Swiss Group for Clinical Cancer Research (SAKK). Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Eur J Cancer. 1997 Jun;33(7):1017-24. link to original article PubMed
  10. SWOG S8312: Russell CA, Green SJ, O'Sullivan J, Hynes HE, Budd GT, Congdon JE, Martino S, Osborne CK. Megestrol acetate and aminoglutethimide/hydrocortisone in sequence or in combination as second-line endocrine therapy of estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group phase III trial. J Clin Oncol. 1997 Jul;15(7):2494-501. link to original article PubMed
  11. Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J, Bezwoda W, Gardin G, Gudgeon A, Morgan M, Fornasiero A, Hoffmann W, Michel J, Hatschek T, Tjabbes T, Chaudri HA, Hornberger U, Trunet PF. Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol. 1998 Feb;16(2):453-61. link to original article contains protocol PubMed
  12. Goss PE, Winer EP, Tannock IF, Schwartz LH; North American Vorozole Study Group. Randomized phase III trial comparing the new potent and selective third-generation aromatase inhibitor vorozole with megestrol acetate in postmenopausal advanced breast cancer patients. J Clin Oncol. 1999 Jan;17(1):52-63. link to original article PubMed
  13. CALGB 8741: Abrams J, Aisner J, Cirrincione C, Berry DA, Muss HB, Cooper MR, Henderson IC, Panasci L, Kirshner J, Ellerton J, Norton L. Dose-response trial of megestrol acetate in advanced breast cancer: Cancer and Leukemia Group B phase III study 8741. J Clin Oncol. 1999 Jan;17(1):64-73. link to original article contains protocol PubMed
  14. Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Zilembo N, Dugardyn JL, Nasurdi C, Mennel RG, Cervek J, Fowst C, Polli A, di Salle E, Arkhipov A, Piscitelli G, Miller LL, Massimini G; The Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. J Clin Oncol. 2000 Apr;18(7):1399-411. link to original article contains protocol PubMed
  15. Buzdar A, Douma J, Davidson N, Elledge R, Morgan M, Smith R, Porter L, Nabholtz J, Xiang X, Brady C. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol. 2001 Jul 15;19(14):3357-66. link to original article contains protocol PubMed

Melphalan monotherapy

back to top

P: Phenylalanine mustard (Melphalan)

Regimen

Study Evidence Comparator Comparative Efficacy
Canellos et al. 1976 Phase III (C) CMF Seems to have inferior OS

Chemotherapy

42-day cycles

References

  1. Canellos GP, Pocock SJ, Taylor SG 3rd, Sears ME, Klaasen DJ, Band PR. Combination chemotherapy for metastatic breast carcinoma: prospective comparison of multiple drug therapy with L-phenylalanine mustard. Cancer. 1976 Nov;38(5):1882-6. link to original article PubMed

Methotrexate & Thiotepa

back to top

Regimen

Study Evidence
Greenspan et al. 1963 Non-randomized

Note: this is possibly the first published trial of combination chemotherapy in breast cancer.

Chemotherapy

References

  1. Greenspan EM, Fieber M, Lesnick G, Edelman S. Response of advanced breast carcinoma to the combination of the antimetabolite, Methotrexate, and the alkylating agent, thio-TEPA. J Mt Sinai Hosp N Y. 1963 May-Jun;30:246-67. PubMed

Mitoxantrone monotherapy

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Harris et al. 1990 Non-randomized portion of RCT
Cowan et al. 1991 (SWOG S8203) Phase III (C) 1. Bisantrene
2. Doxorubicin 		Seems to have inferior OS

Chemotherapy

21-day cycles

References

  1. Harris AL, Cantwell BM, Carmichael J, Wilson R, Farndon J, Dawes P, Ghani S, Evans RG. Comparison of short-term and continuous chemotherapy (mitozantrone) for advanced breast cancer. Lancet. 1990 Jan 27;335(8683):186-90. link to original article PubMed
  2. SWOG S8203: Cowan JD, Neidhart J, McClure S, Coltman CA Jr, Gumbart C, Martino S, Hutchins LF, Stephens RL, Vaughan CB, Osborne CK. Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study. J Natl Cancer Inst. 1991 Aug 7;83(15):1077-84. link to original article contains protocol PubMed

STAMP-I

back to top

Regimen

Study Evidence Comparator Comparative Efficacy
Vredenburgh et al. 2006 Phase III (E-esc) Observation Superior EFS

Preceding treatment

  • Duke AFM x 2 to 4

Chemotherapy

References

  1. Vredenburgh JJ, Madan B, Coniglio D, Ross M, Broadwater G, Niedzwiecki D, Edwards J, Marks L, Vandemark R, McDonald C, Affronti ML, Peters WP. A randomized phase III comparative trial of immediate consolidation with high-dose chemotherapy and autologous peripheral blood progenitor cell support compared to observation with delayed consolidation in women with metastatic breast cancer and only bone metastases following intensive induction chemotherapy. Bone Marrow Transplant. 2006 Jun;37(11):1009-15. link to original article PubMed

TAD (Tamoxifen)

back to top

TAD: Tamoxifen, Aminoglutethimide, Danazol

Regimen

Study Evidence Comparator Comparative Efficacy
Powles et al. 1984 Phase III (E-esc) Tamoxifen Seems to have superior ORR

Note: this patient population was not selected by hormone receptor status.

Hormonotherapy

References

  1. Powles TJ, Ashley S, Ford HT, Gazet JC, Nash AG, Neville AM, Coombes RC. Treatment of disseminated breast cancer with tamoxifen, aminoglutethimide, hydrocortisone, and danazol, used in combination or sequentially. Lancet. 1984 Jun 23;1(8391):1369-73. link to original article PubMed

Thiotepa monotherapy

back to top

Regimen

Study Evidence
Bateman 1955 Non-randomized

Chemotherapy

References

  1. Bateman JC. Chemotherapy of solid tumors with triethylene thiophosphoramide. N Engl J Med. 1955 May 26;252(21):879-87. link to original article PubMed

VAC (Adriamycin)

back to top

VAC: Vincristine, Adriamycin (Doxorubicin), Cyclophosphamide

Regimen

Study Evidence Comparator Comparative Efficacy
Gundersen et al. 1986 Phase III (C) Doxorubicin Seems not superior
Powles et al. 1991 Phase III (C) 3M Did not meet primary endpoint of ORR
Green et al. 1996 Phase III (C) VNC Might have superior ORR

Used as a comparator arm in older trials and found to be more toxic; here for reference purposes only.

Chemotherapy

References

  1. 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. link to SD article PubMed
  2. Powles TJ, Jones AL, Judson IR, Hardy JR, Ashley SE. A randomised trial comparing combination chemotherapy using mitomycin C, mitozantrone and methotrexate (3M) with vincristine, anthracycline and cyclophosphamide (VAC) in advanced breast cancer. Br J Cancer. 1991 Aug;64(2):406-10. link to original article PubMed
  3. Green JA, Slater AJ, Campbell IR, Kelly V. Advanced breast cancer: a randomized study of doxorubicin or mitoxantrone in combination with cyclophosphamide and vincristine. Breast Cancer Res Treat. 1996;39(2):155-63. link to original article PubMed

VAP

back to top

VAP: Vincristine, Adriamycin (Doxorubicin), Prednisolone

Regimen

Study Evidence Comparator Comparative Efficacy
Leonard et al. 1987 Phase III (C) VMP Seems not superior

Chemotherapy

Hormonotherapy

References

  1. Leonard RC, Cornbleet MA, Kaye SB, Soukop M, White G, Hutcheon AW, Robinson S, Kerr ME, Smyth JF. Mitoxantrone versus doxorubicin in combination chemotherapy for advanced carcinoma of the breast. J Clin Oncol. 1987 Jul;5(7):1056-63. link to original article PubMed
Retrieved from "https://hemonc.org/w/index.php?title=Complex_multipart_regimens&oldid=41447"