Breast cancer - historical

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

44 regimens on this page 63 variants on this page

Adjuvant therapy

CMFP

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CMFP: Cyclophosphamide, Methotrexate, Fluorouracil, Prednisone

Regimen

Study	Evidence	Comparator	Efficacy
Mansour et al. 1989 (ECOG E1180)	Phase III (E)	No further treatment	Superior DFS
Tormey et al. 1990 (ECOG E5177)	Phase III	CMF CMFPT	Seems not superior

Preceding treatment

• Modified radical mastectomy or a total mastectomy with low axillary-node dissection

Chemotherapy

• Cyclophosphamide (Cytoxan)
• Methotrexate (MTX)
• Fluorouracil (5-FU)
• Prednisone (Sterapred)

28-day cycle for 6 to 12 cycles

References

1. ECOG E1180: Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med. 1989 Feb 23;320(8):485-90. link to original article PubMed
2. ECOG E5177: Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. link to original article PubMed

CTCb, then auto HSCT

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CTCb: Cyclophosphamide, Thiotepa, Carboplatin

Regimen

Study	Evidence	Comparator	Efficacy
Rodenhuis et al. 2003	Phase III (E)	FEC x 5	Might have superior RFS

No longer used, but of historical interest.

Preceding treatment

• FEC x 4

Chemotherapy

• Cyclophosphamide (Cytoxan)
• Thiotepa (Thioplex)
• Carboplatin (Paraplatin)

References

1. Rodenhuis S, Bontenbal M, Beex LV, Wagstaff J, Richel DJ, Nooij MA, Voest EE, Hupperets P, van Tinteren H, Peterse HL, TenVergert EM, de Vries EG; Netherlands Working Party on Autologous Transplantation in Solid Tumors. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med. 2003 Jul 3;349(1):7-16. link to original article PubMed

MV

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MV: Methotrexate & Vinblastine

Regimen

Study	Evidence	Comparator	Efficacy
Assikis et al. 2003	Phase III	See link	See link

Preceding treatment

• FAC x 6

Chemotherapy

• Methotrexate (MTX) 75 mg/m² IV once on day 1
• Vinblastine (Velban) 1.7 mg/m²/day continuous infusion on days 1 to 5

Supportive medications

• Folinic acid (Leucovorin) rescue

21- to 28-day cycle for 4 cycles

References

1. Assikis V, Buzdar A, Yang Y, Smith T, Theriault R, Booser D, Valero V, Walters R, Singletary E, Ames F, Hortobagyi G. A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003 Jun 1;97(11):2716-23. link to original article contains protocol PubMed

Observation

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Regimen

Study	Evidence	Comparator	Efficacy
Bonadonna et al. 1976	Phase III (C)	CMF	Inferior RFS
Mansour et al. 1989 (ECOG E1180)	Phase III (C)	CMFP	Inferior DFS
Henderson et al. 2003 (INT 0148/CALGB 9344)	Phase III (C)	Paclitaxel q3wk	Inferior OS
Mamounas et al. 2005 (NSABP B-28)	Phase III (C)	Paclitaxel q3wk	Inferior DFS

No further treatment.

Preceding treatment

• Bonadonna et al. 1976: Mastectomy
• ECOG E1180: Modified radical mastectomy or a total mastectomy with low axillary-node dissection
• INT 0148/CALGB 9344: Surgery, then AC x 4 versus high-dose AC x 4 versus very-high-dose AC x 4
• NSABP B-28: Surgery, then AC x 4

References

1. Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, De Lena M, Tancini G, Bajetta E, Musumeci R, Veronesi U. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976 Feb 19;294(8):405-10. link to original article PubMed
   1. Update: Bonadonna G, Rossi A, Valagussa P, Banfi A, Veronesi U. The CMF program for operable breast cancer with positive axillary nodes. Updated analysis on the disease-free interval, site of relapse and drug tolerance. Cancer. 1977 Jun;39(6 Suppl):2904-15. link to original article PubMed
   2. Update: Bonadonna G, Valagussa P, Rossi A, Tancini G, Brambilla C, Zambetti M, Veronesi U. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat. 1985;5(2):95-115. PubMed
   3. Update: Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995 Apr 6;332(14):901-6. link to original article PubMed
2. ECOG E1180: Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med. 1989 Feb 23;320(8):485-90. link to original article PubMed
3. INT 0148/CALGB 9344: Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. link to original article contains verified protocol PubMed
4. NSABP B-28: Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. link to original article PubMed

Paclitaxel monotherapy, q3wk

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

Variant #1, 175 mg/m² q3wk

Study	Evidence	Comparator	Efficacy
Henderson et al. 2003 (INT 0148/CALGB 9344)	Phase III	Observation	Superior OS
Citron et al. 2003 (CALGB 9741)	Non-randomized portion of RCT
Romond et al. 2005 (NSABP B-31)	Phase III	TH	Inferior OS
Sparano et al. 2008 (ECOG E1199)	Phase III	Weekly Paclitaxel	Inferior OS
		Docetaxel q3wk	Seems to have inferior DFS
		Docetaxel weekly	Seems not superior
Del Mastro et al. 2015 (GIM2)	Phase III	See link	See link
Earl et al. 2017 (tAnGo)	Phase III	TG	Seems not superior

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in NSABP B-31 were HER2-positive.

Preceding treatment

• INT 0148/CALGB 9344: AC x 4 versus high-dose AC x 4 versus very-high-dose AC x 4
• CALGB 9741, NSABP B-31, and ECOG E1199: AC x 4
• GIM2: EC x 4 versus FEC x 4
• tAnGo: EC x 4

Chemotherapy

• Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

21-day cycle for 4 cycles

Variant #2, 225 mg/m² q3wk

Study	Evidence	Comparator	Efficacy
Mamounas et al. 2005 (NSABP B-28)	Phase III	Observation	Superior PFS

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Preceding treatment

• AC x 4

Chemotherapy

• Paclitaxel (Taxol) 225 mg/m² IV over 3 hours once on day 1

21-day cycle for 4 cycles

References

1. INT 0148/CALGB 9344: Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. link to original article contains verified protocol PubMed
2. CALGB 9741: Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. link to original article contains verified protocol PubMed
3. NSABP B-28: Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. link to original article PubMed
4. NCCTG N9831: Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. link to original article PubMed
   1. Update: Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4491-7. Epub 2011 Oct 31. link to original article link to PMC article PubMed
   2. Update: Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. link to original article link to PMC article PubMed
   3. Update and HRQoL analysis: Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE Jr, Swain SM, Jeong JH, Fehrenbacher L, Gross HM, Brufsky AM, Flynn PJ, Wahl TA, Seay TE, Wade JL 3rd, Biggs DD, Atkins JN, Polikoff J, Zapas JL, Mamounas EP, Wolmark N. Long-term follow-up of cardiac function and quality of life for patients in NSABP protocol B-31/NRG Oncology: a randomized trial comparing the safety and efficacy of doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel and trastuzumab in patients with node-positive breast cancer with tumors overexpressing human epidermal growth factor receptor 2. J Clin Oncol. 2017 Dec 10;35(35):3942-3948. Epub 2017 Oct 26. link to original article link to PMC article PubMed
5. ECOG E1199: Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. link to original article link to PMC article PubMed
   1. Update: Sparano JA, Zhao F, Martino S, Ligibel JA, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer. J Clin Oncol. 2015 Jul 20;33(21):2353-60. Epub 2015 Jun 15. link to original article link to PMC article PubMed
6. GIM2: Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella (GIM) investigators. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. Epub 2015 Mar 2. link to original article contains verified protocol PubMed
7. tAnGo: Earl HM, Hiller L, Howard HC, Dunn JA, Young J, Bowden SJ, McDermaid M, Waterhouse AK, Wilson G, Agrawal R, O'Reilly S, Bowman A, Ritchie DM, Goodman A, Hickish T, McAdam K, Cameron D, Dodwell D, Rea DW, Caldas C, Provenzano E, Abraham JE, Canney P, Crown JP, Kennedy MJ, Coleman R, Leonard RC, Carmichael JA, Wardley AM, Poole CJ; tAnGo trial collaborators. Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):755-769. Epub 2017 May 4. link to original article contains protocol PubMed

Placebo

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Regimen

Study	Evidence	Comparator	Efficacy
Fisher et al. 1975	Phase III	Melphalan	Seems to have inferior DFS

No active antineoplastic treatment after mastectomy. Used as a comparator arm, historically; here for reference purposes only.

References

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

Metastatic disease, combination chemotherapy

CTCb

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CTCb: Cyclophosphamide, Thiotepa, Carboplatin

Regimen

Study	Evidence	Comparator	Efficacy
Stadtmauer et al. 2000 (Philadelphia Bone Marrow Transplant Group)	Phase III (E)	CMF	Seems not superior

No longer used, but of historical interest.

Chemotherapy

• Cyclophosphamide (Cytoxan)
• Thiotepa (Thioplex)
• Carboplatin (Paraplatin)

References

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

VAC (Adriamycin)

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VAC: Vincristine, Adriamycin (Doxorubicin), Cyclophosphamide

Regimen

Study	Evidence	Comparator	Efficacy
Gundersen et al. 1986	Phase III	Doxorubicin	Seems not superior

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

Chemotherapy

• Vincristine (Oncovin)
• Doxorubicin (Adriamycin)
• Cyclophosphamide (Cytoxan)

References

1. Gundersen S, Kvinnsland S, Klepp O, Kvaløy S, Lund E, Høst H. Weekly adriamycin versus VAC in advanced breast cancer: a randomized trial. Eur J Cancer Clin Oncol. 1986 Dec;22(12):1431-4. link to SD article PubMed