Breast cancer - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main breast cancer page for current regimens.
Last updated on 2024-09-06:50 regimens on this page
70 variants on this page
 
=Neoadjuvant therapy=
==CVAP==
CVAP: Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), Prednisone
VACP: Vincristine, Adriamycin (Doxorubicin), Cyclophosphamide, Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence
Thomas et al. 2004b	1985-1989 	Non-randomized part of RCT
====Chemotherapy====
*Cyclophosphamide (Cytoxan) as follows:
**Cycle 1: 600 mg/m2 IV over 15 minutes once on day 1
**Cycle 2: 700 mg/m2 IV over 15 minutes once on day 1
**Cycle 3: 750 mg/m2 IV over 15 minutes once on day 1
*Vincristine (Oncovin) by the following age-based criteria:
**Younger than 50 years old: 1.5 mg/m2 (maximum dose of 2 mg) IV once on day 1
**Older than 50 years old: 1.5 mg/m2 (maximum dose of 1.5 mg) IV once on day 1
*Doxorubicin (Adriamycin) as follows:
**Cycle 1: 60 mg/m2 IV continuous infusion over 72 hours, started on day 1
**Cycle 2: 70 mg/m2 IV continuous infusion over 72 hours, started on day 1
**Cycle 3: 75 mg/m2 IV continuous infusion over 72 hours, started on day 1
====Endocrine therapy====
*Prednisone (Sterapred) 40 mg PO once per day on days 1 to 5
21-day cycle for 3 cycles
====Subsequent treatment====
*Surgery
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==CVAP (Prednisolone)==
CVAP: Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), Prednisolone
VACP: Vincristine, Adriamycin (Doxorubicin), Cyclophosphamide, Prednisolone
===Regimen===
Study 	Dates of enrollment	Evidence
Smith et al. 2002	1996-07 to 1999-03 	Non-randomized part of RCT
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
====Endocrine therapy====
*Prednisolone (Millipred) 40 mg PO once per day on days 1 to 5
21-day cycle for 4 cycles
====Subsequent treatment====
*Smith et al. 2002, responders: Neoadjuvant CVAP x 4 versus D x 4, then Surgery
*Smith et al. 2002, nonresponders: Neoadjuvant D x 4, then Surgery
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
=Adjuvant therapy, sequential regimens=
==ddEC-ECT==
ddEC-ECT: dose-dense Epirubicin & Cyclophosphamide followed by Epirubicin, Cyclophosphamide, Thiotepa
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Nitz et al. 2005 (WSG AM-01)	1995-2002 	Phase 3 (E-esc)	ddEC-ddCMF	Longer EFS (primary endpoint)Median EFS: 76.1 vs 40.6 mo(HR not reported, p=0.00069)Seems to have longer OS (secondary endpoint)Median OS: NYR vs 75.9 mo(HR not reported, p=0.02)
No longer used, but of historical interest.
====Preceding treatment====
*Surgery
====Chemotherapy, ddEC portion (cycles 1 & 2)====
*Epirubicin (Ellence) 90 mg/m2 IV over 60 minutes once on day 1, given first
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV over 60 to 120 minutes once on day 1, given second
====Supportive therapy, ddEC portion (cycles 1 & 2)====
*Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 12
====Chemotherapy, ECT portion (cycles 3 & 4)====
*Epirubicin (Ellence) 90 mg/m2 IV over 60 minutes once on day -5, given first
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 2 to 3 hours once per day on days -5 to -3, given second (total dose: 3000 mg/m2)
*Thiotepa (Thioplex) 133 mg/m2 IV over 2 to 3 hours once per day on days -5 to -3, given third (total dose: 400 mg/m2)
====Supportive therapy, ECT portion (cycles 3 & 4)====
*Mesna (Mesnex)
*Autologous stem cells reinfused on day 0
14-day cycle for 2 cycles, then 2 courses (ddEC x 2; ECT x 2)
===References===
# WSG AM-01: Nitz UA, Mohrmann S, Fischer J, Lindemann W, Berdel WE, Jackisch C, Werner C, Ziske C, Kirchner H, Metzner B, Souchon R, Ruffert U, Schütt G, Pollmanns A, Schmoll HJ, Middecke C, Baltzer J, Schrader I, Wiebringhaus H, Ko Y, Rösel S, Schwenzer T, Wernet P, Hinke A, Bender HG, Frick M; West German Study Group. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial. Lancet. 2005 Dec 3;366(9501):1935-44. Erratum in: Lancet. 2006 Mar 4;367(9512):730. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==FAC-MV==
FAC-MV: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, followed by Methotrexate & Vinblastine
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Assikis et al. 2003	1986-1994 	Phase 3 (E-switch-ooc)	Tamoxifen 	Did not meet primary endpoint of OS
====Preceding treatment====
*Surgery
====Chemotherapy, FAC portion (cycles 1 to 6)====
*Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
*Doxorubicin (Adriamycin) 16.7 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 50 mg/m2)
*Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
====Chemotherapy, MV portion (cycles 7 to 10)====
*Methotrexate (MTX) 75 mg/m2 IV once on day 1
*Vinblastine (Velban) 1.7 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 8.5 mg/m2)
====Supportive therapy, MV portion (cycles 7 to 10)====
*Leucovorin (Folinic acid) 8 mg/m2 PO every 6 hours for 8 doses, starting 24 hours after methotrexate
21- to 28-day cycle for 10 cycles (FAC x 6; MV x 4)
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Adjuvant therapy=
==AVCF==
AVCF: Adriamycin (Doxorubicin), Vincristine, Cyclophosphamide, Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Misset et al. 1996 (OncoFrance)	1978-1981 	Phase 3 (E-esc)	CMF 	Longer OS
Note: OncoFrance was one of the studies analyzed in the 1998 EBCTCG meta-analysis that supported FDA approval of doxorubicin for this indication.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Doxorubicin (Adriamycin) 30 mg/m2 (maximum dose of 50 mg) IV once on day 1
*Vincristine (Oncovin) 1 mg/m2 IV once on day 2
*Cyclophosphamide (Cytoxan) 300 mg/m2 IV once per day on days 3 to 6
*Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 3 to 6
Monthly cycle for 12 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# Meta-analysis: Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet. 1998 Sep 19;352(9132):930-42. link to original article EuroPMC
==AVCMF==
AVCMF: Adriamycin (Doxorubicin), Vinblastine, Cyclophosphamide, Methotrexate, Fluorouracil
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Ploner et al. 2003 (ABCSG 3)	1984 to not reported	Randomized (E-esc)	CMF 	Did not meet endpoints of DFS/OS
Note: ABCSG 3 was one of the studies analyzed in the 1998 EBCTCG meta-analysis that supported FDA approval of doxorubicin for this indication.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Doxorubicin (Adriamycin)
*Vinblastine (Velban)
*Cyclophosphamide (Cytoxan)
*Methotrexate (MTX)
*Fluorouracil (5-FU)
===References===
# Meta-analysis: Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet. 1998 Sep 19;352(9132):930-42. link to original article EuroPMC
# 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; ABCSG. 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 dosing details not available in abstract EuroPMC
==CAMFP==
CAMFP: Cyclophosphamide, Adriamycin (Doxorubicin), Methotrexate, Fluorouracil, Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Recht et al. 1996	1984-1992 	Phase 3 (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====
*Lumpectomy
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 3
*Methotrexate (MTX) 200 mg/m2 IV once per day on days 1 & 15
*Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
====Endocrine therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
====Supportive therapy====
*Leucovorin (Folinic acid) 10 mg/m2 PO four times per day on days 2 to 4, 16 to 18
21-day cycle for 4 cycles
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CEF/CMF==
CEF/CMF: Cyclophosphamide, Epirubicin, Fluorouracil alternating with Cyclophosphamide, Methotrexate, Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Bedognetti et al. 2011	1985-1992 	Phase 3 (C)	CEFT/CMFT 	Did not meet primary endpoint of OS
====Preceding treatment====
*Surgery
====Chemotherapy, CEF portion (cycles 1, 3, 5, 7, 9, 11)====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Epirubicin (Ellence) 60 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
====Chemotherapy, CMF portion (cycles 2, 4, 6, 8, 10, 12)====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Methotrexate (MTX) 40 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
21-day cycle for 12 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==CFP==
CFP: Cyclophosphamide, Fluorouracil, Prednisone
===Regimen variant #1, weight-based===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Caprini et al. 1980	1975-1979 	Phase 3 (E-esc)	1. Melphalan	Seems to have longer DFS
Caprini et al. 1980	1975-1979 	Phase 3 (E-esc)	2. CFP & BCG	Did not meet primary endpoint of DFS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 4 mg/kg IV once per day on days 1 to 5
*Fluorouracil (5-FU) 8 mg/kg IV once per day on days 1 to 5
====Endocrine therapy====
*Prednisone (Sterapred) 30 mg PO once per day on days 1 to 7
42-day cycle for 9 cycles
===Regimen variant #2, BSA-based===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Ahmann et al. 1978	Not reported 	Phase 3 (E-esc)	Melphalan 	Seems to have longer OS
Note: Ahmann et al. 1978 had several other arms that closed early in the study and were not included in the analysis.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 150 mg/m2 IV push once per day on days 1 to 5
*Fluorouracil (5-FU) 300 mg/m2 IV push once per day on days 1 to 5
====Endocrine therapy====
*Prednisone (Sterapred) 30 mg PO once per day on days 1 to 7
42-day cycle for 10 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==CMFP==
CMFP: Cyclophosphamide, Methotrexate, Fluorouracil, Prednisone
===Regimen variant #1, 6 cycles with low-dose prednisone===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Goldhirsch et al. 1988 (IBCSG V)	1981-1985 	Phase 3 (C)	CMFL x 1 	Seems to have longer OS
====Preceding treatment====
*Modified radical mastectomy or total mastectomy with low axillary-node dissection
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
*Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
*Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
====Endocrine therapy====
*Prednisone (Sterapred) 7.5 mg PO once per day on days 1 to 28
28-day cycle for 6 cycles
===Regimen variant #2, 6 cycles with high-dose prednisone===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mansour et al. 1989 (ECOG E1180)	1981-1988 	Phase 3 (E-esc)	No further treatment	Longer DFS
Note: ECOG E1180 is also known as INT-0011.
====Preceding treatment====
*Modified radical mastectomy or total mastectomy with low axillary-node dissection
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
*Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
*Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
====Endocrine therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
28-day cycle for 6 cycles
===Regimen variant #3, 12 cycles===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tormey et al. 1990 (ECOG E5177)	1978-1982 	Phase 3 (E-esc)	1. CMF2. CMFPT	Did not meet co-primary endpoints of time to response/OS
====Preceding treatment====
*Modified radical mastectomy or total mastectomy with low axillary-node dissection
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
*Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
*Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
====Endocrine therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
28-day cycle for 12 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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. EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==CMFPT==
CMFPT: Cyclophosphamide, Methotrexate, Fluorouracil, Prednisone, Tamoxifen
===Regimen variant #1, 6 cycles===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Goldhirsch et al. 1988 (IBCSG V)	1981-1985 	Phase 3 (C)	CMFL x 1 	Seems to have longer OS
====Preceding treatment====
*Modified radical mastectomy or total mastectomy with low axillary-node dissection
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
*Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
*Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
====Endocrine therapy====
*Prednisone (Sterapred) 7.5 mg PO once per day on days 1 to 28
*Tamoxifen (Nolvadex) 20 mg PO once per day on days 1 to 28
28-day cycle for 6 cycles
===Regimen variant #2, 12 cycles with low-dose prednisone===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Goldhirsch et al. 1984 (LBCS III)	1978-1981 	Phase 3 (E-esc)	1. Observation	Longer DFS
Goldhirsch et al. 1984 (LBCS III)	1978-1981 	Phase 3 (E-esc)	2. PT 	Seems to have longer DFS
====Preceding treatment====
*Modified radical mastectomy or total mastectomy with low axillary-node dissection
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
*Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
*Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
====Endocrine therapy====
*Prednisone (Sterapred) 7.5 mg PO once per day on days 1 to 28
*Tamoxifen (Nolvadex) 20 mg PO once per day on days 1 to 28
28-day cycle for 12 cycles
===Regimen variant #3, 12 cycles with high-dose prednisone===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Tormey et al. 1990 (ECOG E5177)	1978-1982 	Phase 3 (E-esc)	1. CMF2. CMFP	Did not meet co-primary endpoints of time to response/OS
Falkson et al. 1990 	1982 to not reported	Phase 3 (C) 	CMFPT x 4 	Did not meet primary endpoint of DFS
Tormey et al. 1992 (ECOG E5181)	1982-02 to 1987-06 	Phase 3 (C) 	CMFPTH/ALTER 	Seems to have longer time to response
====Preceding treatment====
*Modified radical mastectomy or total mastectomy with low axillary-node dissection
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
*Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
*Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
====Endocrine therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
*Tamoxifen (Nolvadex) 10 mg PO twice per day on days 1 to 28
28-day cycle for 12 cycles
====Subsequent treatment====
*ECOG E5181: Adjuvant Tamoxifen x 4 y versus no further treatment
===References===
# LBCS III: 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# LBCS 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# Falkson HC, Gray R, Wolberg WH, Gillchrist KW, Harris JE, Tormey DC, Falkson G; ECOG. 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# ECOG E5181: Tormey DC, Gray R, Abeloff MD, Roseman DL, Gilchrist KW, Barylak EJ, Stott P, Falkson G. Adjuvant therapy with a doxorubicin regimen and long-term tamoxifen in premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 1992 Dec;10(12):1848-56. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CMFVP==
CMFVP: Cyclophosphamide, Methotrexate, Fluorouracil, Vincristine, Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Glucksberg et al. 1982 (SWOG S7436)	1975-1978 	Randomized (E-esc) 	Melphalan 	Longer OS
Tormey et al. 1983a 	1975-1980 	Phase 3 (E-esc) 	1. CMF 	Longer DFS
Tormey et al. 1983a 	1975-1980 	Phase 3 (E-esc) 	2. CMF-MER 	Not reported
Rivkin et al. 1993 (SWOG S7827ER-) 	1979-1984 	Phase 3 (C) 	CMFVP x 2 y 	Did not meet co-primary endpoints of DFS/OS
Rivkin et al. 1996 (SWOG S7821) 	1979-1989 	Randomized (C) 	CMFVP & Oophorectomy	Did not meet co-primary endpoints of DFS/OS
Perloff et al. 1996 (CALGB 8082) 	1980-1984 	Non-randomized part of RCT	 	
Budd et al. 1995 (SWOG S8313) 	1984-1990 	Phase 3 (C) 	FAC-M 	Might have longer DFS
Note: it is not clear from Rivkin et al. 1993 whether prednisone was stopped after the 6th week, and what the tapering schedule was.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 60 mg/m2 PO once per day on days 1 to 7
*Methotrexate (MTX) 15 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 400 mg/m2 IV once on day 1
*Vincristine (Oncovin) as follows:
**Cycles 1 to 10: 0.625 mg/m2 IV once on day 1
====Endocrine therapy====
*Prednisone (Sterapred) as follows:
**Cycles 1 to 6: 30 mg/m2/day PO tapering to 10 mg/m2/day PO
7-day cycle for 52 cycles (1 year)
===References===
# 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 EuroPMC
##Update: Rivkin SE, Green S, Metch B, Glucksberg H, Gad-el-Mawla N, Constanzi JJ, Hoogstraten B, Athens J, Maloney T, Osborne CK, Vaughn CB. Adjuvant CMFVP versus melphalan for operable breast cancer with positive axillary nodes: 10-year results of a Southwest Oncology Group Study. J Clin Oncol. 1989 Sep;7(9):1229-38. link to original article EuroPMC
## 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 EuroPMC
# 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 EuroPMC
# SWOG S7827ER-: 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 EuroPMC
# CALGB 8082: Perloff M, Norton L, Korzun AH, Wood WC, Carey RW, Gottlieb A, Aust JC, Bank A, Silver RT, Saleh F, Canellos GP, Perry MC, Weiss RB, Holland JF. Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: a Cancer and Leukemia Group B study. J Clin Oncol. 1996 May;14(5):1589-98. link to original article EuroPMC
==CPB==
CPB: Cyclophosphamide, Platinol (Cisplatin), BCNU (Carmustine)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Peters et al. 2005 (CALGB 9082)	1991-1998 	Phase 3 (E-de-esc)	HD-CPB with auto HSCT	Did not meet primary endpoint of EFS
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, then adjuvant FAC x 3
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 900 mg/m2 IV over 60 minutes once per day on days 1 to 3
*Cisplatin (Platinol) 30 mg/mg2/day IV continuous infusion over 72 hours, started on day 1 (total dose: 90 mg/m2)
*Carmustine (BCNU) 90 mg/m2 IV over 18 hours once on day 3
One course
====Subsequent treatment====
*Adjuvant FAC x 1
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==CTCb, then auto HSCT==
CTCb: Cyclophosphamide, Thiotepa, Carboplatin
STAMP-V
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Eder et al. 1990 	1987-1988 	Phase 1/2 	 	
Rodenhuis et al. 1998 	1991-1995 	Randomized Phase 2 (E-esc)	Standard adjuvant therapy	Did not meet co-primary endpoints of DFS/OS
Rodenhuis et al. 2003 (Dutch National Study)	1993-1999 	Phase 3 (E-esc) 	FEC x 5 	Did not meet primary endpoint of OS1
Bergh et al. 2000 (SBG 9401) 	1994-1998 	Phase 3 (C) 	See link 	See link
1Reported efficacy for the Dutch National Study is based on the 2020 update.
====Preceding treatment====
*Rodenhuis et al. 1998: Neoadjuvant FEC x 3, then surgery, then adjuvant FEC x 1
*Dutch National Study: Adjuvant FEC x 4
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1500 mg/m2/day IV on days -7 to -4
*Thiotepa (Thioplex) 125 mg/m2/day IV on days -7 to -4
*Carboplatin (Paraplatin) 200 mg/m2/day IV on days -7 to -4
====Supportive therapy====
*Autologous stem cells re-infused on day 0
One course
===References===
# 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 EuroPMC
# 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 EuroPMC
# 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. 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 original article EuroPMC
# Dutch National Study: 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 EuroPMC NCT03087409
## Update: Rodenhuis S, Bontenbal M, van Hoesel QG, Smit WM, Nooij MA, Voest EE, van der Wall E, Hupperets P, van Tinteren H, Peterse JL, van de Vijver MJ, de Vries EG; Netherlands Working Party on Autologous Transplantation in Solid Tumours. Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer. Ann Oncol. 2006 Apr;17(4):588-96. Epub 2006 Jan 30. link to original article EuroPMC
## Update: Steenbruggen TG, Steggink LC, Seynaeve CM, van der Hoeven JJM, Hooning MJ, Jager A, Konings IR, Kroep JR, Smit WM, Tjan-Heijnen VCG, van der Wall E, Bins AD, Linn SC, Schaapveld M, Jacobse JN, van Leeuwen FE, Schröder CP, van Tinteren H, de Vries EGE, Sonke GS, Gietema JA. High-Dose Chemotherapy With Hematopoietic Stem Cell Transplant in Patients With High-Risk Breast Cancer and 4 or More Involved Axillary Lymph Nodes: 20-Year Follow-up of a Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Apr 1;6(4):528-534. link to original article link to PMC article EuroPMC
==Cyclophosphamide monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Brinker et al. 1983 (DBCG 77B)	1977-1983 	Phase 3 (E-esc) 	1. CMF 	Did not meet primary endpoint of RFS
Brinker et al. 1983 (DBCG 77B)	1977-1983 	Phase 3 (E-esc) 	2. Observation 	Seems to have longer OS1
Brinker et al. 1983 (DBCG 77B)	1977-1983 	Phase 3 (E-esc) 	3. Levamisole 	Not reported
Killander et al. 2009 	1978-1983 	Phase 3 (E-switch-ooc)	1. RT2. Cyclophosphamide & RT	Not reported
1Reported efficacy for DBCG 77B is based on the 2010 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 130 mg/m2 PO once per day on days 1 to 14
1-month cycle for 12 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
#Killander F, Anderson H, Rydén S, Möller T, Hafström LO, Malmström P. Efficient reduction of loco-regional recurrences but no effect on mortality twenty years after postmastectomy radiation in premenopausal women with stage II breast cancer - a randomized trial from the South Sweden Breast Cancer Group. Breast. 2009 Oct;18(5):309-15. Epub 2009 Oct 6. link to original article EuroPMC
==Cyclophosphamide & Doxorubicin (AC)==
AC: Adriamycin (Doxorubicin) and Cyclophosphamide
CA: Cyclophosphamide and Adriamycin (Doxorubicin)
===Regimen variant #1, 54/1200 x 6===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Linden et al. 2007 (INT-0137)	1994-1997 	Phase 3 (C)	A-C 	Did not meet primary endpoint of DFS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Doxorubicin (Adriamycin) 54 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===Regimen variant #2, 60/600 x 4===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Fisher et al. 1997 (NSABP B-18) 	1988-1993 	Phase 3 (C) 	AC; neoadjuvant 	Lower resectability
Fisher et al. 1997 (NSABP B-22) 	1989-1991 	Phase 3 (C) 	1. AC; intensified2. AC; intensified & increased 	Did not meet co-primary endpoints of DFS/OS
Fisher et al. 2001 (NSABP B-23) 	1991-1998 	Phase 3 (E-switch-ic)	CMF 	Did not meet primary endpoint of OS
Içli et al. 2001 	1992-1996 	Phase 3 (C) 	AC-EP 	Did not meet primary endpoint of OS
Henderson et al. 2003 (INT 0148/CALGB 9344)	1994-1999 	Phase 3 (C) 	1. AC; high-dose2. AC; very high-dose 	Did not meet primary endpoint of DFS
Henderson et al. 2003 (INT 0148/CALGB 9344)	1994-1999 	Phase 3 (C) 	3. AC-T4. AC-T; high-dose AC5. AC-T; very high-dose AC	Shorter OS
Mamounas et al. 2005 (NSABP B-28) 	1995-1998 	Phase 3 (C) 	AC-T 	Shorter DFS (co-primary endpoint)DFS60: 72% vs 76%(HR 1.20, 95% CI 1.05-1.39)
Jones et al. 2006 (USOR 9735) 	1997-1999 	Phase 3 (C) 	TC 	Shorter DFS (primary endpoint)DFS60: 80% vs 86%(HR 1.49, 95% CI 1.06-2.00)
Goldstein et al. 2008 (ECOG E2197) 	1998-2000 	Phase 3 (C) 	AT 	Did not meet primary endpoint of DFS
Brain et al. 2005 (RAPP-01) 	1999-2003 	Phase 3 (C) 	AT 	Not reported
Muss et al. 2009 (CALGB 49907) 	2001-2006 	Phase 3 (C) 	Capecitabine 	Seems to have longer OS1 (secondary endpoint)RFS120: 56% vs 50%(HR 0.80, 95% CI 0.62-0.98)Seems to have longer RFS (primary endpoint)
Geyer et al. 2022 (NSABP B-36) 	2004-05-20 to 2008-07-25	Phase 3 (C) 	FEC-100 x 6 	Did not meet primary endpoint of DFS
Sparano et al. 2018 (TAILORx) 	2006-2010 	Phase 3 (C) 	No chemotherapy 	Non-inferior IDFS (primary endpoint)
1Reported efficacy for CALGB 49907 is based on the 2019 update.
====Eligibility criteria====
*TAILORx: Oncotype DX score of 11 to 25
====Preceding treatment====
*Surgery
*INT 0148/CALGB 9344: Surgery, within 84 days
====Chemotherapy====
*Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
====Subsequent treatment====
*NSABP B-23: Adjuvant tamoxifen x 5 y versus placebo
===Regimen variant #3, 80/600 x 4===
Study 	Dates of enrollment	Evidence
Moore et al. 2007 (SWOG S9623)	1996-2001 	Non-randomized part of phase 3 RCT
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Doxorubicin (Adriamycin) 80 mg/m2 IV once on day 1 
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
====Subsequent treatment====
*STAMP-I or STAMP-V, with auto HSCT consolidation
===References===
# NSABP B-22: Fisher B, Anderson S, Wickerham DL, DeCillis A, Dimitrov N, Mamounas E, Wolmark N, Pugh R, Atkins JN, Meyers FJ, Abramson N, Wolter J, Bornstein RS, Levy L, Romond EH, Caggiano V, Grimaldi M, Jochimsen P, Deckers P. Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22. J Clin Oncol. 1997 May;15(5):1858-69. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
# NSABP B-18: Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB Jr, Fisher ER, Wickerham DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NV. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997 Jul;15(7):2483-93. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. link to original article EuroPMC
## Update: Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst. 2001;(30):96-102. link to original article EuroPMC
## 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 EuroPMC
## Pooled update: Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. link to original article EuroPMC
# NSABP B-23: Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. link to original article EuroPMC
## Update: Fisher B, Jeong JH, Anderson S, Wolmark N. Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials. J Natl Cancer Inst. 2004 Dec 15;96(24):1823-31. link to original article EuroPMC
# Içli F, Akbulut H, Dinçol D, Onur H, Demirkazik A, Cam R, Cay F, Demirci S, Uner A, Erekul S. A randomized trial of four cycles of adjuvant AC (adriamycin + cyclophosphamide) +/- two cycles of EP (etoposide + cisplatin) in node positive patients with breast cancer. Ann Oncol. 2001 Jul;12(7):1011-3. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# RAPP-01: Brain EG, Bachelot T, Serin D, Kirscher S, Graic Y, Eymard JC, Extra JM, Combe M, Fourme E, Noguès C, Rouëssé J; RAPP-01 Trial Investigators. Life-threatening sepsis associated with adjuvant doxorubicin plus docetaxel for intermediate-risk breast cancer. JAMA. 2005 May 18;293(19):2367-71. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# USOR 9735: Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006 Dec 1;24(34):5381-7. Erratum in: J Clin Oncol. 2007 May 1;25(13):1819. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
## Update: Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology research trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83. Epub 2009 Feb 9. link to original article EuroPMC
# INT-0137: Linden HM, Haskell CM, Green SJ, Osborne CK, Sledge GW Jr, Shapiro CL, Ingle JN, Lew D, Hutchins LF, Livingston RB, Martino S. Sequenced compared with simultaneous anthracycline and cyclophosphamide in high-risk stage I and II breast cancer: final analysis from INT-0137 (S9313). J Clin Oncol. 2007 Feb 20;25(6):656-61. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# SWOG S9623: Moore HC, Green SJ, Gralow JR, Bearman SI, Lew D, Barlow WE, Hudis C, Wolff AC, Ingle JN, Chew HK, Elias AD, Livingston RB, Martino S; SWOG. Intensive dose-dense compared with high-dose adjuvant chemotherapy for high-risk operable breast cancer: Southwest Oncology Group/Intergroup study 9623. J Clin Oncol. 2007 May 1;25(13):1677-82. Epub 2007 Apr 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00002772
# ECOG E2197: Goldstein LJ, O'Neill A, Sparano JA, Perez EA, Shulman LN, Martino S, Davidson NE. Concurrent doxorubicin plus docetaxel is not more effective than concurrent doxorubicin plus cyclophosphamide in operable breast cancer with 0 to 3 positive axillary nodes: North American Breast Cancer Intergroup Trial E 2197. J Clin Oncol. 2008 Sep 1;26(25):4092-9. Epub 2008 Aug 4. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT00003519
# CALGB 49907: Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Becker HP, Kartcheske PA, Wheeler JD, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Magrinat G, Parker BA, Hart RD, Grenier D, Norton L, Hudis CA, Winer EP; CALGB. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009 May 14;360(20):2055-65. Erratum in: N Engl J Med. 2009 Oct 22;361(17):1714. Magrinat, Gutav [corrected to Magrinat, Gustav]. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00024102
##Update: Muss HB, Polley MC, Berry DA, Liu H, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Kartcheske PA, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Sutton LM, Magrinat G, Parker BA, Hart RD, Grenier D, Hurria A, Jatoi A, Norton L, Hudis CA, Winer EP, Carey L. Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial. J Clin Oncol. 2019 Sep 10;37(26):2338-2348. Epub 2019 Jul 24. link to original article link to PMC article EuroPMC
# TAILORx: Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Goetz MP, Olson JA Jr, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW Jr. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018 Jul 12;379(2):111-121. Epub 2018 Jun 3. link to original article link to PMC article dosing details in supplement have been reviewed by our editors EuroPMC NCT00310180
#NSABP B-36: Geyer CE Jr, Bandos H, Rastogi P, Jacobs SA, Robidoux A, Fehrenbacher L, Ward PJ, Polikoff J, Brufsky AM, Provencher L, Paterson AHG, Hamm JT, Carolla RL, Baez-Diaz L, Julian TB, Swain SM, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing six cycles of FEC-100 to four cycles of AC in women with operable node-negative breast cancer: the NSABP B-36 trial (NRG Oncology). Breast Cancer Res Treat. 2022 Jun;193(3):555-564. Epub 2022 Mar 1. Erratum in: Breast Cancer Res Treat. 2022 May 4. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00087178
#ASTER 70s: NCT01564056
==FAC & BCG==
FAC & BCG: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, BCG
===Regimen===
Study 	Dates of enrollment	Evidence
Buzdar et al. 1979	1974-1977 	Non-randomized
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 & 8
*Doxorubicin (Adriamycin) as follows:
**Cycles 1 to 7: 40 mg/m2 IV once on day 1
**Cycle 8: 20 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 400 mg/m2 IV once on day 1
====Immunotherapy====
*BCG vaccine by scarification once per day on days 9, 16, 23
28-day cycle for 8 cycles
====Subsequent treatment====
*CMF & BCG maintenance for a total of 2 years of treatment
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==Fluorouracil & Methotrexate (MF)==
MF: Methotrexate & 5-Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Shapiro et al. 1993 	1976-1985 	Phase 3 (C) 	CMF 	Did not meet endpoints of TTF/OS
Fisher et al. 1989 (NSABP B-13)	1981-1988 	Phase 3 (E-esc)	Observation	Longer DFS1
Fisher et al. 1996 (NSABP B-19)	1988-1990 	Phase 3 (C) 	CMF 	Might have shorter OS
1Reported efficacy for NSABP B-13 is based on the 1996 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Methotrexate (MTX) 60 mg/m2 IV once per day on days 1 & 8
*Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 8 cycles
===References===
# 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 EuroPMC
## 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 EuroPMC
## Update: Fisher B, Jeong JH, Anderson S, Wolmark N. Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials. J Natl Cancer Inst. 2004 Dec 15;96(24):1823-31. link to original article EuroPMC
## 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
## Update: Fisher B, Jeong JH, Anderson S, Wolmark N. Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials. J Natl Cancer Inst. 2004 Dec 15;96(24):1823-31. link to original article EuroPMC
## 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 EuroPMC
==FNC==
FNC: Fluorouracil, Novantrone (Mitoxantrone), Cyclophosphamide
CNF: Cyclophosphamide, Novantrone (Mitoxantrone), Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Ron et al. 2001 	1988-1992 	Phase 3 (E-switch-ic)	CMF 	Seems to have longer DFSMedian DFS: 4.4 vs 2.7 years(HR not reported, p=0.04)
Fountzilas et al. 2004 (HE 10/92)	1992-1998 	Phase 3 (C) 	Tamoxifen 	Did not meet primary endpoint of RFS
Toledano et al. 2007 (ARCOSEIN) 	1996-2000 	Phase 3 (C) 	FNC & RT 	Did not meet primary endpoint of DFS
====Preceding treatment====
*Breast-conserving surgery
====Chemotherapy====
*Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
*Mitoxantrone (Novantrone) 12 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 6 cycles
====Subsequent treatment====
*ARCOSEIN: RT
===References===
# 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 EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==Levamisole monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Rojas et al. 1976 	Not reported 	Randomized (E-esc) 	Observation	Seems to have longer OS
Brincker et al. 1980	Not reported 	Randomized (E-switch-ooc)	RT 	Seems to have shorter 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====
*Levamisole (Ergamisol) 150 mg PO once per day on days 1 to 3
14-day cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# Brincker H, Mouridsen HT, Andersen KW, Andersen J, Castberg T, Fischermann K, Henriksen E, Hou-Jensen C, Johansen H, Rossing N, Rorth M; 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 EuroPMC
==Melphalan monotherapy==
P: Phenylalanine mustard (Melphalan)
===Regimen variant #1, 0.15 mg/kg x 9===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Caprini et al. 1980	1975-1979 	Phase 3 (C)	1. CFP2. CFP & BCG	Seems to have shorter DFS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Melphalan (Alkeran) 0.15 mg/kg PO once per day on days 1 to 5
42-day cycle for 9 cycles
===Regimen variant #2, 0.15 mg/kg x 18===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Fisher et al. 1975 (NSABP B-05)	1972-1974 	Phase 3 (E-esc)	Placebo 	Might have longer DFS1
1Reported efficacy for NSABP B-05 is based on the 1986 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Melphalan (Alkeran) 0.15 mg/kg PO once per day on days 1 to 5
42-day cycle for up to 18 cycles (2 years)
===Regimen variant #3, 5 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Glucksberg et al. 1982 (SWOG S7436)	1975-1978 	Randomized (C)	CMFVP 	Shorter OS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Melphalan (Alkeran) 5 mg/m2 PO once per day on days 1 to 5
42-day cycle for up to 18 cycles (2 years)
===Regimen variant #4, 6 mg/m2 x 10===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Ahmann et al. 1978	Not reported 	Phase 3 (C)	CFP 	Seems to have shorter OS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Melphalan (Alkeran) 6 mg/m2 PO once per day on days 1 to 5
42-day cycle for 10 cycles
===Regimen variant #5, 6 mg/m2 x 18===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Fisher et al. 1977 (NSABP B-07)	1975-02-03 to 1976-05-25	Phase 3 (C)	PF 	Seems to have shorter RFS
Note: Fisher et al. 1977 is an update for NSABP B-05 and also the primary results for NSABP B-07.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Melphalan (Alkeran) 6 mg/m2 PO once per day on days 1 to 5
42-day cycle for up to 18 cycles (2 years)
===Regimen variant #6, 6 mg/m2 with dose cap===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Rubens et al. 1983	1975-1979 	Phase 3 (E-esc)	Observation	Might have longer RFS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Melphalan (Alkeran) 6 mg/m2 (maximum dose of 10 mg) PO once per day on days 1 to 5
42-day cycle for up to 16 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
## 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
##Update: Rivkin SE, Green S, Metch B, Glucksberg H, Gad-el-Mawla N, Constanzi JJ, Hoogstraten B, Athens J, Maloney T, Osborne CK, Vaughn CB. Adjuvant CMFVP versus melphalan for operable breast cancer with positive axillary nodes: 10-year results of a Southwest Oncology Group Study. J Clin Oncol. 1989 Sep;7(9):1229-38. link to original article EuroPMC
## 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==PAF==
PAF: Phenylalanine mustard (Melphalan), Adriamycin (Doxorubicin), Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Fisher et al. 1989 (NSABP B-11)	1981-1984 	Phase 3 (E-esc)	PF 	Seems to have longer OS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Melphalan (Alkeran) 4 mg/m2 PO once per day on days 1 to 5
*Doxorubicin (Adriamycin) as follows:
**Cycles 1 to 5: 30 mg/m2 IV once per day on days 1 & 22
*Fluorouracil (5-FU) 300 mg/m2 IV once per day on days 1 to 5
42-day cycle for 17 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==PF==
PF: Phenylalanine mustard (Melphalan) & Fluorouracil
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Fisher et al. 1977 (NSABP B-07)	1975-02-03 to 1976-05-25	Phase 3 (E-esc)	P 	Seems to have longer RFS
Fisher et al. 1980 (NSABP B-08)	1976-04 to 1977-04 	Phase 3 (C) 	PFM 	Did not meet endpoint of OS
Fisher et al. 1981 (NSABP B-09)	1977-1980 	Phase 3 (C) 	PFT 	Shorter RFS
Fisher et al. 1990 (NSABP B-10)	1977-1981 	Phase 3 (C) 	PFCp 	Did not meet endpoints of DFS/OS
Fisher et al. 1989 (NSABP B-11)	1981-1984 	Phase 3 (C) 	PAF 	Seems to have shorter OS
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
====Chemotherapy====
*Melphalan (Alkeran) 4 mg/m2 PO once per day on days 1 to 5
*Fluorouracil (5-FU) 300 mg/m2 IV once per day on days 1 to 5
42-day cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 EuroPMC
## 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 EuroPMC
## 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 EuroPMC
# 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 EuroPMC
# 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 EuroPMC
==Radiation therapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Brincker et al. 1980	Not reported 	Randomized (C)	Levamisole	Seems to have longer RFS
====Preceding treatment====
*Surgery
====Radiotherapy====
*External beam radiotherapy
One course
===References===
# Brincker H, Mouridsen HT, Andersen KW, Andersen J, Castberg T, Fischermann K, Henriksen E, Hou-Jensen C, Johansen H, Rossing N, Rorth M; 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 EuroPMC
==Thiotepa monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Fisher et al. 1968 (NSABP B-01)	1958-1961 	Phase 3 (E-esc)	Placebo 	Did not meet primary endpoint of RR
Note: Day 0 is the day of surgery.
====Chemotherapy====
*Thiotepa (Tepadina) 0.2 mg/kg IV once per day on days 0 to 2
3-day course
===References===
# NSABP B-01: Fisher B, Ravdin RG, Ausman RK, Slack NH, Moore GE, Noer RJ. Surgical adjuvant chemotherapy in cancer of the breast: results of a decade of cooperative investigation. Ann Surg. 1968 Sep;168(3):337-56. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Fisher B, Slack N, Katrych D, Wolmark N. Ten year follow-up results of patients with carcinoma of the breast in a co-operative clinical trial evaluating surgical adjuvant chemotherapy. Surg Gynecol Obstet. 1975 Apr;140(4):528-34. EuroPMC
==TMF==
TMF: Thiotepa, Methotrexate, Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence
Semiglazov et al. 1994	1985-1990 	Non-randomized part of RCT
====Preceding treatment====
*TMF induction followed by RT versus RT followed by Mastectomy
====Chemotherapy====
*Thiotepa (Thioplex) 20 mg IM once per day on days 1, 3, 5, 7, 9, 11
*Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
*Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
28- to 42-day cycle for 4 to 6 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
=Metastatic disease, all lines of therapy=
==CAMF==
CAMF: Cyclophosphamide, Adriamycin (Doxorubicin), Methotrexate, Fluorouracil
AFCM: Adriamycin (Doxorubicin), Fluorouracil, Cyclophosphamide, Methotrexate
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Bezwoda et al. 1979	1976-1977 	Randomized (E-switch-ic)	CMFV 	Did not meet primary endpoint of ORR
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 400 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
*Methotrexate (MTX) 35 mg/m2 IV once on day 8
*Fluorouracil (5-FU) 350 mg/m2 IV once on day 8
28-day cycles
===Regimen variant #2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tranum et al. 1978	Not reported 	Randomized (E-esc)	1. AF2. FAC	Did not meet primary endpoint of ORR
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 300 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) as follows:
**Cycles 1 to 4, 9 to 12, 17 to 20: 40 mg/m2 IV once on day 1
*Methotrexate (MTX) 10 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 300 mg/m2 IV once per day on days 1 & 8
21-day cycles
===Regimen variant #3===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Lippman et al. 1984	1977-1982 	Randomized (C)	CAMFTP 	Did not meet endpoint of ORR
Note: To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 1 (up to a maximum cumulative dose of 525 mg/m2)
*Methotrexate (MTX) 40 mg/m2 IV once on day 8
*Fluorouracil (5-FU) 500 mg/m2 IV once on day 8, given 60 minutes after methotrexate
21-day cycles
===References===
# 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; SWOG. 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==CAFVP==
CAFVP: Cyclophosphamide, Adriamycin (Doxorubicin), Fluorouracil, Vincristine, Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Muss et al. 1978 	1975-05 to 1976-08 	Phase 3 (E-switch-ic)	CMFVP 	Might have longer OS
Aisner et al. 1987 (CALGB 7682)	1976-1980 	Phase 3 (E-esc) 	1. CAF 	Not reported
Aisner et al. 1987 (CALGB 7682)	1976-1980 	Phase 3 (E-esc) 	2. CMF 	Higher ORR
Note: this was "Phase I" of treatment; see paper for details of continuation.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) as follows:
**Cycle 1: 2 mg/kg PO once per day on days 1 to 14, then 100 mg PO once per day on days 15 to 28
**Cycles 2 to 8: 100 mg PO once per day on days 1 to 28
*Doxorubicin (Adriamycin) as follows:
**Cycles 1 to 7: 20 mg/m2 IV once per day on days 1 & 15
**Cycle 8: 20 mg/m2 IV once on day 1
*Fluorouracil (5-FU) as follows:
**Cycle 1: 12 mg/kg IV once per day on days 1 to 3, 15
**Cycles 2 to 8: 12 mg/kg IV once per day on days 1 & 15
*Vincristine (Oncovin) as follows:
**Cycles 1 & 2: 25 mcg/kg IV once per day on days 1 & 15
**Cycles 3 to 8: 25 mcg/kg IV once on day 15
====Endocrine therapy====
*Prednisone (Sterapred) as follows:
**Cycle 1: 0.75 mg/kg PO once per day on days 1 to 14, then 10 mg PO once per day on days 15 to 28
**Cycles 2 to 8: 10 mg PO once per day on days 1 to 28
28-day cycle for 8 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# CALGB 7482: Tormey DC, Weinberg VE, Leone LA, Glidewell OJ, Perloff M, Kennedy BJ, Cortes E, Silver RT, Weiss RB, Aisner J, Holland JF. A comparison of intermittent vs continuous and of adriamycin vs methotrexate 5-drug chemotherapy for advanced breast cancer: A Cancer and Leukemia Group B study. Am J Clin Oncol. 1984 Jun;7(3):231-9. link to original article EuroPMC
# CALGB 7682: Aisner J, Weinberg V, Perloff M, Weiss R, Perry M, Korzun A, Ginsberg S, Holland JF; CALGB. Chemotherapy versus chemoimmunotherapy (CAF v CAFVP v CMF each +/- MER) for metastatic carcinoma of the breast: a CALGB study. J Clin Oncol. 1987 Oct;5(10):1523-33. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==CEFT==
CEFT: Cyclophosphamide, Epirubicin, Fluorouracil, Tamoxifen
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ejlertsen et al. 1993	1986-1989 	Phase 3 (E-de-esc)	CEFT x 18 mo	Shorter OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV bolus once on day 1
*Epirubicin (Ellence) 60 mg/m2 IV bolus once on day 1 
*Fluorouracil (5-FU) 600 mg/m2 IV bolus once on day 1
====Endocrine therapy====
*Tamoxifen (Nolvadex) 30 mg PO once per day on days 1 to 21
21-day cycle for 8 cycles
===References===
# Ejlertsen B, Pfeiffer P, Pedersen D, Mouridsen HT, Rose C, Overgaard M, Sandberg E, Kristensen B. Decreased efficacy of cyclophosphamide, epirubicin and 5-fluorouracil in metastatic breast cancer when reducing treatment duration from 18 to 6 months. Eur J Cancer. 1993;29A(4):527-31. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CFP==
CFP: Cyclophosphamide, Fluorouracil, Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Creagan et al. 1984 	Not reported 	Phase 3 (C) 	CAP-CFP 	Did not meet primary endpoint of ORR
Rosner et al. 1987 	1981-1985 	Randomized (E-de-esc)	1. CA2. CMFVP	Did not meet primary endpoint of OS
Marschke et al. 1989	1982-1987 	Randomized (C) 	CMFP 	Might have lower ORR
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 150 mg/m2 IV once per day on days 1 to 5
*Fluorouracil (5-FU) 300 mg/m2 IV once per day on days 1 to 5
====Endocrine therapy====
*Prednisone (Sterapred) 40 mg PO once per day, tapered to 10 mg PO once per day (details of taper not provided)
35-day cycles
===References===
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
==Chlorambucil & Prednisolone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Freckman et al. 1964	1955-1963 	Non-randomized	 	
Løber et al. 1983 	1978-1980 	Phase 3 (C) 	1. Prednimustine; continuous 	Shorter TTP
Løber et al. 1983 	1978-1980 	Phase 3 (C) 	2. Prednimustine; intermittent	Might have shorter TTP
Note: Per Freckman et al. 1964, chlorambucil was continued until moderate leukopenia, and then adjusted further.
====Chemotherapy====
*Chlorambucil (Leukeran) 10 mg PO twice per day
====Endocrine therapy====
*Prednisolone (Millipred) 10 mg PO three times per day on days 1 to 14, then 10 mg PO twice per day on days 15 to 21, then 10 to 15 mg/day PO
Continued indefinitely (see note)
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# Løber J, Mouridsen HT, Christiansen IE, Dombernowsky P, Mattsson W, Rørth M. A phase III trial comparing prednimustine (LEO 1031) to chlorambucil plus prednisolone in advanced breast cancer. Cancer. 1983 Nov 1;52(9):1570-6. link to original article EuroPMC
==CMFP==
CMFP: Cyclophosphamide, Methotrexate, Fluorouracil, Prednisone
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Canellos et al. 1974 	Not reported 	Non-randomized 	 	
Segaloff et al. 1985 	1971-1976 	Phase 3 (C) 	CMFVP 	Did not meet primary endpoint of OS
Tormey et al. 1982 (ECOG E2173)	1973-1974 	Randomized (E-esc)	1. AV2. CMF	Seems to have longer OS
Cummings et al. 1985 	1978-1979 	Randomized (E-esc)	CAF 	Did not meet primary endpoint of ORR
Marschke et al. 1989 	1982-1987 	Randomized (E-esc)	CFP 	Might have higher ORR
Bishop et al. 1999 	1993 to not reported	Phase 3 (C) 	Paclitaxel 	Seems to have shorter OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
*Methotrexate (MTX) 40 mg/mg2 IV once per day on days 1 & 8
*Fluorouracil (5-FU) 600 mg/mg2 IV once per day on days 1 & 8
====Endocrine therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
28-day cycle for 6 cycles
===References===
# Canellos GP, Devita VT, Gold GL, Chabner BA, Schein PS, Young RC. Cyclical combination chemotherapy for advanced breast carcinoma. BMJ. 1974 Feb 9;1(5901):218-20. link to original article link to PMC article EuroPMC
# 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 EuroPMC
# 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 EuroPMC
# 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 EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==CMFV==
CMFV: Cyclophosphamide, Methotrexate, Fluorouracil, Vinblastine
CVMF: Cyclophosphamide, Vinblastine, Methotrexate, Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Edelstyn et al. 1975	Not reported 	Randomized (E-esc)	CMFV; 1-day	Higher ORR
Bezwoda et al. 1979 	1976-1977 	Randomized (C) 	CAMF 	Did not meet primary endpoint of ORR
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 400 mg/m2 IV once on day 1
*Methotrexate (MTX) 35 mg/m2 IV once on day 8
*Fluorouracil (5-FU) 350 mg/m2 IV once on day 8
*Vinblastine (Velban) 6 mg/m2 IV once on day 1
28-day cycles
===References===
# 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 original article EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==CMFVP==
CMFVP: Cyclophosphamide, Methotrexate, Fluorouracil, Vincristine, Prednisone
COMFP: Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Fluorouracil, Prednisone
CFPMV: Cyclophosphamide, Fluorouracil, Prednisone, Methotrexate, Vincristine
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Segaloff et al. 1985 	1971-1976 	Phase 3 (E-esc) 	CMFP 	Did not meet primary endpoint of OS
Hoogstraten et al. 1976 	1972-1974 	Phase 3 (E-esc) 	Doxorubicin	Seems to have higher ORR
Smalley et al. 1977 	1974-04-01 to 1975-07-01	Phase 3 (C) 	CAF 	Might have shorter OS1
Muss et al. 1978 	1975-05 to 1976-08 	Phase 3 (C) 	CAFVP 	Might have shorter OS
Carmo-Pereira et al. 1980	Not reported 	Phase 3 (E-esc) 	5-FU 	Longer OS
Rosner et al. 1987 	1981-1985 	Randomized (E-esc)	1. CA2. CFP	Did not meet primary endpoint of OS
1Reported efficacy for Smalley et al. 1977 is based on the 1983 update.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) as follows:
**Cycles 1, 2, 5, 6, 9, 10, 13, 14, 17, 18: 75 mg/m2 PO once per day on days 1 to 7
*Methotrexate (MTX) 15 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 300 mg/m2 IV once on day 1
*Vincristine (Oncovin) 0.65 mg/m2 IV once on day 1
====Endocrine therapy====
*Prednisone (Sterapred) 20 mg/m2 PO once per day with taper (details not provided)
7-day cycle for 20 cycles
===References===
# Hoogstraten B, George SL, Samal B, Rivkin SE, Costanzi JJ, Bonnet JD, Thigpen T, Braine H; SWOG. 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 EuroPMC
# Smalley RV, Carpenter J, Bartolucci A, Vogel C, Krauss S; Southeastern Cancer Study Group. A comparison of cyclophosphamide, adriamycin, 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone (CMFVP) in patients with metastatic breast cancer: a Southeastern Cancer Study Group project. Cancer. 1977 Aug;40(2):625-32. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
# 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 EuroPMC
# 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 original article dosing details in manuscript have been reviewed by our editors EuroPMC
# CALGB 7482: Tormey DC, Weinberg VE, Leone LA, Glidewell OJ, Perloff M, Kennedy BJ, Cortes E, Silver RT, Weiss RB, Aisner J, Holland JF. A comparison of intermittent vs continuous and of adriamycin vs methotrexate 5-drug chemotherapy for advanced breast cancer: A Cancer and Leukemia Group B study. Am J Clin Oncol. 1984 Jun;7(3):231-9. link to original article EuroPMC
# 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 EuroPMC
# 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 EuroPMC
==Cyclophosphamide monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Rubens et al. 1975	1970-1974 	Phase 3 (C)	CMFV 	Did not meet primary endpoint of ORR
Miles et al. 2011 	1998-2003 	Phase 3 (C)	STn-KLH vaccine	Did not meet co-primary endpoints of TTP/OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) by the following weight-based criteria:
**Less than 48 kg: 200 mg PO once per day 
**48 to 58 kg: 250 mg PO once per day
**More than 58 kg: 300 mg PO once per day
Continued indefinitely
===References===
# 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 link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
# Miles D, Roché H, Martin M, Perren TJ, Cameron DA, Glaspy J, Dodwell D, Parker J, Mayordomo J, Tres A, Murray JL, Ibrahim NK; Theratope® Study Group. Phase III multicenter clinical trial of the sialyl-TN (STn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer. Oncologist. 2011;16(8):1092-100. Epub 2011 May 14. link to original article link to PMC article EuroPMC
==Doxorubicin & Etoposide==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Vaughn et al. 1988 (SWOG S8020)	1980-1982 	Phase 3 (E-esc)	Doxorubicin	Seems to have longer TTP
====Chemotherapy====
*Doxorubicin (Adriamycin) as follows:
**Cycles 1 to 15: 30 mg/m2 IV once on day 1
*Etoposide (Vepesid) 50 mg/m2 (route not specified) once per day on days 1 to 5
21-day cycles
===References===
# SWOG S8020: Vaughn CB, Green SJ, O'Bryan R, Reed M, Grozea PN, Fletcher WS, Green JB, Metch B, Oishi N. VP-16 + adriamycin vs adriamycin alone in advanced adenocarcinoma of the breast, phase II, a randomized trial: a Southwest Oncology Group Study. Med Pediatr Oncol. 1988;16(5):312-9. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Fluorouracil monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Carmo-Pereira et al. 1980	Not reported 	Phase 3 (C)	CMFVP 	Shorter OS
Note: To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Fluorouracil (5-FU) as follows:
**Cycle 1: 500 mg/m2 IV once per day on days 1 to 5
**Cycle 2 onwards: 500 mg/m2 IV once on day 1
7-day cycles
===References===
# 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 original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Fluorouracil & Methotrexate (MF)==
MF: Methotrexate & 5-Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Sjöström et al. 1999	1994-1997 	Phase 3 (C)	Docetaxel 	Shorter TTP (primary endpoint)Median TTP: 3 vs 6.3 mo(aHR 1.59, 95% CI 1.18-2.17)
Note: To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Methotrexate (MTX) 200 mg/m2 IV over 15 minutes once per day on days 1 & 8, given first
*Fluorouracil (5-FU) 600 mg/m2 IV bolus once per day on days 1 & 8, given second, one hour after methotrexate
21-day cycles
===References===
# Sjöström J, Blomqvist C, Mouridsen H, Pluzanska A, Ottosson-Lönn S, Bengtsson NO, Ostenstad B, Mjaaland I, Palm-Sjövall M, Wist E, Valvere V, Anderson H, Bergh J; Scandinavian Breast Group. Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group. Eur J Cancer. 1999 Aug;35(8):1194-201. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Melphalan monotherapy==
P: Phenylalanine mustard (Melphalan)
===Regimen variant #1, 25 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Jones et al. 1995a	1990-1992 	Phase 3 (C)	Vinorelbine	Seems to have shorter OS
Note: To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Melphalan (Alkeran) 25 mg/m2 IV once on day 1
28-day cycles
===Regimen variant #2, 30 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Canellos et al. 1976	Not reported 	Phase 3 (C)	CMF 	Seems to have shorter OS
Note: To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Melphalan (Alkeran) 6 mg/m2 PO once per day on days 1 to 5
42-day cycles
===References===
# 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 EuroPMC
# Jones S, Winer E, Vogel C, Laufman L, Hutchins L, O'Rourke M, Lembersky B, Budman D, Bigley J, Hohneker J. Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer. J Clin Oncol. 1995 Oct;13(10):2567-74. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Methotrexate & Thiotepa==
===Regimen===
Study 	Evidence
Greenspan et al. 1963	Non-randomized
Note: this is possibly the first published trial of combination chemotherapy in breast cancer. Treatment details are not available for online review.
====Chemotherapy====
*Methotrexate (MTX)
*Thiotepa (Tepadina)
===References===
# 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. dosing details not available in abstract EuroPMC
==Mitoxantrone monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Harris et al. 1990 	Not reported 	Non-randomized part of RCT	 	
Cowan et al. 1991 (SWOG S8203)	1983-1986 	Phase 3 (C) 	1. Bisantrene2. Doxorubicin	Seems to have shorter OS
====Chemotherapy====
*Mitoxantrone (Novantrone) 14 mg/m2 IV once on day 1
21-day cycles
===References===
# 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 EuroPMC
# 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 dosing details in abstract have been reviewed by our editors EuroPMC
==Thiotepa monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Bateman 1955	Not reported 	Non-randomized
====Chemotherapy====
*Thiotepa (Thioplex) by varying doses and routes; see paper for details
===References===
# Bateman JC. Chemotherapy of solid tumors with triethylene thiophosphoramide. N Engl J Med. 1955 May 26;252(21):879-87. link to original article EuroPMC
=Metastatic disease, first-line therapy=
==CAV==
CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine
VAC: Vincristine, Adriamycin (Doxorubicin), Cyclophosphamide
===Regimen variant #1, 1/40/600===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Muss et al. 1982	1979-1981 	Randomized (E-esc)	CMF 	Seems to have higher ORR
====Chemotherapy====
*Vincristine (Oncovin) 1 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 200 mg/m2 PO once per day on days 3 to 5
21-day cycles
===Regimen variant #2, 1.4/30/400===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Powles et al. 1991	1985-1989 	Phase 3 (C)	3M 	Did not meet primary endpoint of ORR
====Chemotherapy====
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
*Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 400 mg/m2 IV once on day 1
21-day cycles
===Regimen variant #3, 1.4/50/600===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Green et al. 1996	Not reported 	Phase 3 (C)	VNC 	Might have higher ORR
====Chemotherapy====
*Vincristine (Oncovin) by the following age-based criteria:
**60 years old or younger: 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
**Older than 60 years old: 1.4 mg/m2 (maximum dose of 1 mg) IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycles
===Regimen variant #4, 1.5/50/500===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Zekan et al. 1984	1981-04 to 1982-10 	Phase 3 (C)	CF 	Did not meet co-primary endpoints
====Chemotherapy====
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 (maximum dose of 100 mg) IV once on day 1
*Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for up to 9 cycles
====Subsequent treatment====
*CF maintenance
===Regimen variant #5, 2/50/600===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gundersen et al. 1986	1982-06 to 1983-12 	Phase 3 (C)	Doxorubicin	Did not meet endpoint of ORR
====Chemotherapy====
*Vincristine (Oncovin) 2 mg IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for up to 10 cycles
====Subsequent treatment====
*CM maintenance
===References===
# Muss HB, Richards F 2nd, Jackson DV, Cooper MR, White DR, Stuart JJ, Ramseur W, Christian RM, Wells HB, Pope E, Spurr CL; Piedmont Oncology Association. Vincristine, doxorubicin, and cyclophosphamide versus low-dose intravenous cyclophosphamide, methotrexate, and 5-fluorouracil in advanced breast cancer: a randomized trial of the Piedmont Oncology Association. Cancer. 1982 Dec 1;50(11):2269-74. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Zekan PJ, Muss HB, Capizzi RL, Cooper MR, Harding RW, Hopkins JO, Jackson DV, Ramseur WL, Richards F 2nd, Spurr CL, Stuart JJ, White DR, Pope E, Case D, Wells HB; Piedmont Oncology Association. High-dose cyclophosphamide and 5-fluorouracil versus vincristine, doxorubicin, and cyclophosphamide in advanced carcinoma of the breast: a phase III study of the Piedmont Oncology Association (POA). Cancer. 1984 Dec 1;54(11):2338-43. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==Mitoxantrone & Vinorelbine (MV)==
MV: Mitoxantrone & Vinorelbine
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Namer et al. 2001	1993-04 to 1995-12 	Phase 3 (E-de-esc)	1a. FAC1b. FEC	Equivalent ORR
====Chemotherapy====
*Mitoxantrone (Novantrone) 12 mg/m2 IV once on day 1
*Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
21-day cycles
===References===
#Namer M, Soler-Michel P, Turpin F, Chinet-Charrot P, de Gislain C, Pouillart P, Delozier T, Luporsi E, Etienne PL, Schraub S, Eymard JC, Serin D, Ganem G, Calais G, Maillart P, Colin P, Trillet-Lenoir V, Prevost G, Tigaud D, Clavère P, Marti P, Romieu G, Wendling JL. Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer. Eur J Cancer. 2001 Jun;37(9):1132-40. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==STAMP-I==
===Regimen===
Study 	Dates of enrollment	Evidence
Peters et al. 1988	Not reported 	Non-randomized
====Chemotherapy====
*Carmustine (BCNU) 600 mg/m2 IV once on day -3
*Cisplatin (Platinol) 55 mg/m2/day IV continuous infusion over 72 hours, started on day -6 (total dose: 165 mg/m2)
*Cyclophosphamide (Cytoxan) 1875 mg/m2 IV once per day on days -6 to -4
====Supportive therapy====
*Autologous stem cells re-infused on days -1, 0, +1
One course
===References===
# Peters WP, Shpall EJ, Jones RB, Olsen GA, Bast RC, Gockerman JP, Moore JO. High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer. J Clin Oncol. 1988 Sep;6(9):1368-76. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==VAP==
VAP: Vincristine, Adriamycin (Doxorubicin), Prednisolone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Leonard et al. 1987	Not reported 	Phase 3 (C)	VMP 	Higher ORR
====Chemotherapy====
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
====Endocrine therapy====
*Prednisolone (Millipred) 40 mg PO once per day on days 1 to 5
21-day cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
=Metastatic disease, consolidation after first-line therapy=
==CHUT, then auto HSCT==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Biron et al. 2007 (Pegase 03)	1995-2001 	Phase 3 (E-esc)	No further treatment	Longer DFS (co-primary endpoint)
====Preceding treatment====
*Induction FEC x 4
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00002870
==CTCb, then auto HSCT==
CTCb: Cyclophosphamide, Thiotepa, Carboplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Stadtmauer et al. 2000	1990-1997 	Phase 3 (E-esc)	CMF 	Did not meet primary endpoint of OS
No longer used, but of historical interest.
====Preceding treatment====
*Stadtmauer et al. 2000, patients who had previously received less than 400 mg/m2 cumulative lifetime doxorubicin dose: Induction FAC x 4 to 6 cycles
*Stadtmauer et al. 2000, patients who had previously received 400 mg/m2 to 500 mg/m2 cumulative lifetime doxorubicin dose: Induction CMF x 4 to 6 cycles or CMFP x 4 to 6 cycles
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1500 mg/m2/day IV continuous infusion over 96 hours, start on day -6 (total dose: 6000 mg/m2)
*Thiotepa (Thioplex) 125 mg/m2/day IV continuous infusion over 96 hours, start on day -6 (total dose: 500 mg/m2)
*Carboplatin (Paraplatin) 200 mg/m2/day IV continuous infusion over 96 hours, start on day -6 (total dose: 800 mg/m2)
====Supportive therapy====
*Autologous stem cells re-infused on day 0
One course
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==STAMP-I==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Vredenburgh et al. 2006	1992-1997 	Phase 3 (E-esc)	Observation	Longer EFS
====Preceding treatment====
*Induction Duke AFM x 2 to 4
====Chemotherapy====
*Carmustine (BCNU) 600 mg/m2 IV once on day -3
*Cisplatin (Platinol) 55 mg/m2/day IV continuous infusion over 72 hours, started on day -6 (total dose: 165 mg/m2)
*Cyclophosphamide (Cytoxan) 1875 mg/m2 IV once per day on days -6 to -4
====Supportive therapy====
*Autologous stem cells re-infused on days -1, 0, +1
One course
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
=Metastatic disease, subsequent lines of therapy=
==Mitomycin & Vinblastine (MV)==
MV: Mitomycin & Vinblastine
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Nabholtz et al. 1999 (TAX 304)	Not reported 	Phase 3 (C)	Docetaxel 	Shorter TTP (primary endpoint)Median TTP: 11 vs 19 weeks(aHR 1.49, 95% CI 1.20-1.89)Shorter OS (secondary endpoint)Median OS: 8.7 vs 11.4 mo(aHR 1.41, 95% CI 1.10-1.79)
====Chemotherapy====
*Mitomycin (Mutamycin) 12 mg/m2 IV over 2 to 5 minutes once on day 1
*Vinblastine (Velban) 6 mg/m2 IV bolus once on day 1
21-day cycle for up to 10 cycles
===Regimen variant #2===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Keller et al. 2004	Not reported 	Phase 3 (C)	PLD 	Might have shorter PFS (primary endpoint)Median PFS: 2.5 vs 2.9 mo(HR 1.27, 95% CI 0.98-1.61)
Note: The timing here has been modified to keep dosing on a consistent day of the week.
====Chemotherapy====
*Mitomycin (Mutamycin) as follows:
**Cycles 1 & 2: 10 mg/m2 IV once per day on days 1 & 29
**Cycle 3 onwards: 10 mg/m2 IV once on day 1
*Vinblastine (Velban) as follows:
**Cycles 1 & 2: 5 mg/m2 IV once per day on days 1, 15, 29, 43
**Cycle 3 onwards: 5 mg/m2 IV once per day on days 1 & 22
8-week cycle for 2 cycles, then 6- to 8-week cycles
===References===
# TAX 304: Nabholtz JM, Senn HJ, Bezwoda WR, Melnychuk D, Deschênes L, Douma J, Vandenberg TA, Rapoport B, Rosso R, Trillet-Lenoir V, Drbal J, Molino A, Nortier JW, Richel DJ, Nagykalnai T, Siedlecki P, Wilking N, Genot JY, Hupperets PS, Pannuti F, Skarlos D, Tomiak EM, Murawsky M, Alakl M, Aapro M; 304 Study Group. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. J Clin Oncol. 1999 May;17(5):1413-24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Keller AM, Mennel RG, Georgoulias VA, Nabholtz JM, Erazo A, Lluch A, Vogel CL, Kaufmann M, von Minckwitz G, Henderson IC, Mellars L, Alland L, Tendler C. Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. J Clin Oncol. 2004 Oct 1;22(19):3893-901. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
Category:Breast cancer regimens
Category:Historical regimens
Category:Disease-specific pages
Category:Malignant breast neoplasm