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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. 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.

22 regimens on this page
23 variants on this page

Contents


Adjuvant therapy

ACT

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ACT: Adriamycin (Doxorubicin), Cyclophosphamide, Tamoxifen

Regimen

Study Evidence Comparator Efficacy
Fisher et al. 1990 (NSABP B-16) Phase III (E) 1. PFT Not reported
2. Tamoxifen Seems to have superior OS

Preceding treatment

Chemotherapy

References

  1. NSABP B-16: Fisher B, Redmond C, Legault-Poisson S, Dimitrov NV, Brown AM, Wickerham DL, Wolmark N, Margolese RG, Bowman D, Glass AG, Kardinal CG, Robidoux A, Jochimsen P, Cronin W, Deutsch M, Fisher ER, Myers DB, Hoehn JL. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990 Jun;8(6):1005-18. link to original article PubMed
    1. Pooled update: Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. link to original article PubMed

CAMFP

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

Regimen

Study Evidence Comparator
Recht et al. 1996 Phase III (*) See note

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

Preceding treatment

Chemotherapy

21-day cycle for 4 cycles

References

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

CFP & Oophorectomy

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

Regimen

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

Preceding treatment

Chemohormonotherapy

References

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

CMFL

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

Regimen

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

Preceding treatment

Chemotherapy

One cycle

References

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

CMFP

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CMFP: Cyclophosphamide, Methotrexate, Fluorouracil, Prednisone

Regimen

Study Evidence Comparator Efficacy
Goldhirsch et al. 1988 (IBCSG V) Phase III (C) CMFL x 1 Seems to have superior OS
Mansour et al. 1989 (ECOG E1180) Phase III (E) No further treatment Superior DFS
Tormey et al. 1990 (ECOG E5177) Phase III (E) 1. CMF
2. CMFPT
Seems not superior

Preceding treatment

Chemotherapy

28-day cycle for 6 to 12 cycles

References

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

CMFPT

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CMFPT: Cyclophosphamide, Methotrexate, Fluorouracil, Prednisone, Tamoxifen

Regimen

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

Preceding treatment

Chemohormonotherapy

28-day cycle for 6 to 12 cycles

References

  1. LBCS III/IV: Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. link to original article PubMed
  2. IBCSG V: Goldhirsch A; Ludwig Breast Cancer Study Group. Combination adjuvant chemotherapy for node-positive breast cancer: inadequacy of a single perioperative cycle. N Engl J Med. 1988 Sep 15;319(11):677-83. link to original article PubMed
  3. ECOG E5177: Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. link to original article PubMed

CTCb, then auto HSCT

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CTCb: Cyclophosphamide, Thiotepa, Carboplatin

Regimen

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

No longer used, but of historical interest.

Preceding treatment

Chemotherapy

References

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

Melphalan monotherapy

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P: Phenylalanine mustard (Melphalan)

Regimen

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

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

Preceding treatment

Chemotherapy

References

  1. NSABP B-05: Fisher B, Carbone P, Economou SG, Frelick R, Glass A, Lerner H, Redmond C, Zelen M, Band P, Katrych DL, Wolmark N, Fisher ER. 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer: a report of early findings. N Engl J Med. 1975 Jan 16;292(3):117-22. link to original article PubMed
    1. Update: Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. link to original article PubMed
    2. Update: Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986 Jun;4(6):929-41. link to original article PubMed
  2. NSABP B-07: Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. link to original article PubMed

MF

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MF: Methotrexate & 5-Fluorouracil

Regimen

Study Evidence Comparator Efficacy
Fisher et al. 1989 (NSABP B-13) Phase III (E) Observation Superior DFS (*)
Fisher et al. 1996 (NSABP B-19) Phase III (E) CMF Might have inferior OS

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

Preceding treatment

Chemotherapy

References

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

MV

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MV: Methotrexate & Vinblastine

Regimen

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

Preceding treatment

Chemotherapy

Supportive medications

21- to 28-day cycle for 4 cycles

References

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

Observation

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Regimen

Study Evidence Comparator Efficacy
Bonadonna et al. 1976 Phase III (C) CMF Inferior RFS
Brinker et al. 1983 (DBCG 77B) Phase III (C) 1. CMF Seems to have inferior OS (*)
2. Cyclophosphamide Seems to have inferior OS (*)
3. Levamisole Seems not superior
Goldhirsch et al. 1984 (LBCS III) Phase III (C) 1. CMFPT Inferior DFS
2. PT Inferior DFS
Goldhirsch et al. 1984 (LBCS IV) Phase III (C) PT Seems to have inferior DFS
Fisher et al. 1989 (NSABP B-13) Phase III (C) Sequential MF Inferior DFS (*)
Mansour et al. 1989 (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 systemic treatment; many of these trials incorporated RT, however (see individual papers for details). Reported efficacy for DBCG 77B is based on the 2010 update. Reported efficacy for NSABP B-13 is based on the 1996 update.

Preceding treatment

References

  1. Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, De Lena M, Tancini G, Bajetta E, Musumeci R, Veronesi U. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976 Feb 19;294(8):405-10. link to original article PubMed
    1. Update: Bonadonna G, Rossi A, Valagussa P, Banfi A, Veronesi U. The CMF program for operable breast cancer with positive axillary nodes: updated analysis on the disease-free interval, site of relapse and drug tolerance. Cancer. 1977 Jun;39(6 Suppl):2904-15. link to original article PubMed
    2. Update: Bonadonna G, Valagussa P, Rossi A, Tancini G, Brambilla C, Zambetti M, Veronesi U. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat. 1985;5(2):95-115. PubMed
    3. Update: Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995 Apr 6;332(14):901-6. link to original article PubMed
  2. DBCG 77B: Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. link to original article contains verified protocol PubMed
    1. Update: Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Andersson M, Kamby C, Knoop AS; Danish Breast Cancer Cooperative Group. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer. Cancer. 2010 May 1;116(9):2081-9. link to original article PubMed
  3. LBCS III/IV: Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. link to original article PubMed
  4. NSABP B-13: Fisher B, Redmond C, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, Glass A, Foster R, Caplan R. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med. 1989 Feb 23;320(8):473-8. link to original article PubMed
    1. Update: Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. link to original article PubMed
    2. Pooled update: Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. link to original article PubMed
  5. 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
  6. LCBS V: Goldhirsch A, Gelber RD; Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med. 1989 Feb 23;320(8):491-6. link to original article PubMed
  7. 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
  8. NSABP B-28: Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. link to original article PubMed

Oophorectomy

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Regimen

Study Evidence Comparator Efficacy
Ahmann et al. 1977 Phase III (C) #CFP_.26_Oophorectomy Seems to have inferior PFS

Preceding treatment

Hormonotherapy

References

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

Paclitaxel monotherapy, q3wk

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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 (E) Observation Superior OS
Citron et al. 2003 (CALGB 9741) Non-randomized portion of RCT
Romond et al. 2005 (NSABP B-31) Phase III (C) TH Inferior OS
Sparano et al. 2008 (ECOG E1199) Phase III (C) 1. Weekly Paclitaxel Inferior OS
2. Docetaxel q3wk Seems to have inferior DFS
3. Docetaxel weekly Seems not superior
Burnell et al. 2009 (NCIC CTG MA.21) Phase III (C) See link See link
Del Mastro et al. 2015 (GIM2) Phase III (C) See link See link
Earl et al. 2017 (tAnGo) Phase III (C) TG Seems not superior

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

Preceding treatment

  • INT 0148/CALGB 9344: Surgery, then AC x 4 versus high-dose AC x 4 versus very-high-dose AC x 4
  • CALGB 9741, NSABP B-31, and ECOG E1199: Surgery, then AC x 4
  • NCIC CTG MA.21: Surgery, then AC x 4 versus ddEC x 6
  • GIM2: Surgery, then EC x 4 versus FEC x 4
  • tAnGo: Surgery, then EC x 4

Chemotherapy

21-day cycle for 4 cycles

Variant #2, 225 mg/m2 q3wk

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

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

Preceding treatment

Chemotherapy

21-day cycle for 4 cycles

References

  1. INT 0148/CALGB 9344: Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. link to original article contains verified protocol PubMed
  2. 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. NCIC CTG MA.21: Burnell M, Levine MN, Chapman JA, Bramwell V, Gelmon K, Walley B, Vandenberg T, Chalchal H, Albain KS, Perez EA, Rugo H, Pritchard K, O'Brien P, Shepherd LE. Cyclophosphamide, epirubicin, and fluorouracil versus dose-dense epirubicin and cyclophosphamide followed by paclitaxel versus doxorubicin and cyclophosphamide followed by paclitaxel in node-positive or high-risk node-negative breast cancer. J Clin Oncol. 2010 Jan 1;28(1):77-82. Epub 2009 Nov 9. link to original article link to PMC article contains verified protocol PubMed
  7. 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
  8. tAnGo: Earl HM, Hiller L, Howard HC, Dunn JA, Young J, Bowden SJ, McDermaid M, Waterhouse AK, Wilson G, Agrawal R, O'Reilly S, Bowman A, Ritchie DM, Goodman A, Hickish T, McAdam K, Cameron D, Dodwell D, Rea DW, Caldas C, Provenzano E, Abraham JE, Canney P, Crown JP, Kennedy MJ, Coleman R, Leonard RC, Carmichael JA, Wardley AM, Poole CJ; tAnGo trial collaborators. Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):755-769. Epub 2017 May 4. link to original article contains protocol PubMed

PAF

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

Regimen

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

Preceding treatment

Chemotherapy

References

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

PF

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PF: Phenylalanine mustard (Melphalan) & Fluorouracil

Regimen

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

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

Preceding treatment

Chemotherapy

References

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

PFT

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

Regimen

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

Preceding treatment

Chemohormonotherapy

References

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

Placebo

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Regimen

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

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

Preceding treatment

References

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

PT

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PT: Prednisone & Tamoxifen

Regimen

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

Preceding treatment

Hormonotherapy

References

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

Metastatic disease, all lines of therapy

Aminoglutethimide & Hydrocortisone

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Regimen

Study Evidence Comparator Efficacy
Santen et al. 1981 Phase III (C) Adrenalectomy Seems not superior

Chemotherapy

Supportive medications

References

  1. Santen RJ, Worgul TJ, Samojlik E, Interrante A, Boucher AE, Lipton A, Harvey HA, White DS, Smart E, Cox C, Wells SA. A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer. N Engl J Med. 1981 Sep 3;305(10):545-51. link to original article PubMed

CFP

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CFP: Cyclophosphamide, Fluorouracil, Prednisone

Regimen

Study Evidence Comparator Efficacy
Creagan et al. 1984 Phase III (C) CAP, then CFP Seems not superior
Marschke et al. 1989 Phase III (C) CMFP Might have inferior ORR

Chemotherapy

References

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

CMFP

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CMFP: Cyclophosphamide, Methotrexate, Fluorouracil, Prednisone

Regimen

Study Evidence Comparator Efficacy
Tormey et al. 1982 Phase III (E) 1. AV
2. CMF
Seems to have superior OS
Marschke et al. 1989 Phase III (E) CFP Might have superior ORR

Chemotherapy

References

  1. Tormey DC, Gelman R, Band PR, Sears M, Rosenthal SN, DeWys W, Perlia C, Rice MA. Comparison of induction chemotherapies for metastatic breast cancer: an Eastern Cooperative Oncology Group Trial. Cancer. 1982 Oct 1;50(7):1235-44. link to original article PubMed
  2. Marschke RF Jr, Ingle JN, Schaid DJ, Krook JE, Mailliard JA, Cullinan SA, Pfeifle DM, Votava HJ, Ebbert LP, Windschitl HE. Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer. Cancer. 1989 May 15;63(10):1931-7. link to original article PubMed

DES monotherapy

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Regimen

Study Evidence Comparator Efficacy
Ingle et al. 1981 Phase III (C) Tamoxifen Seems not superior
Kiang et al. 1981 Phase III (C) Cyclophosphamide, 5-FU, DES Seems to have inferior OS (*)

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

Chemotherapy

References

  1. Ingle JN, Ahmann DL, Green SJ, Edmonson JH, Bisel HF, Kvols LK, Nichols WC, Creagan ET, Hahn RG, Rubin J, Frytak S. Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N Engl J Med. 1981 Jan 1;304(1):16-21. link to original article PubMed
  2. Kiang DT, Frenning DH, Gay J, Goldman AI, Kennedy BJ. Combination therapy of hormone and cytotoxic agents in advanced breast cancer. Cancer. 1981 Feb 1;47(3):452-6. link to original article PubMed
    1. Update: Kiang DT, Gay J, Goldman A, Kennedy BJ. A randomized trial of chemotherapy and hormonal therapy in advanced breast cancer. N Engl J Med. 1985 Nov 14;313(20):1241-6. link to original article PubMed

CTCb, then auto HSCT

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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

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

Fluoxymesterone monotherapy

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Regimen

Study Evidence
Kennedy 1958 Non-randomized

Hormonotherapy

References

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

Megestrol acetate monotherapy

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Regimen

Study Evidence Comparator Efficacy
Abrams et al. 1999 (CALGB 8741) Phase III (C) Higher-dose Megace Seems not superior

Hormonotherapy

Continued indefinitely

References

  1. CALGB 8741: Abrams J, Aisner J, Cirrincione C, Berry DA, Muss HB, Cooper MR, Henderson IC, Panasci L, Kirshner J, Ellerton J, Norton L. Dose-response trial of megestrol acetate in advanced breast cancer: Cancer and Leukemia Group B phase III study 8741. J Clin Oncol. 1999 Jan;17(1):64-73. link to original article contains protocol PubMed

Mitoxantrone monotherapy

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Regimen

Study Evidence
Harris et al. 1990 Non-randomized portion of RCT

Chemotherapy

References

  1. Harris AL, Cantwell BM, Carmichael J, Wilson R, Farndon J, Dawes P, Ghani S, Evans RG. Comparison of short-term and continuous chemotherapy (mitozantrone) for advanced breast cancer. Lancet. 1990 Jan 27;335(8683):186-90. link to original article PubMed

Thiotepa monotherapy

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Regimen

Study Evidence
Bateman 1955 Non-randomized

Chemotherapy

References

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

VAC (Adriamycin)

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VAC: Vincristine, Adriamycin (Doxorubicin), Cyclophosphamide

Regimen

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

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

Chemotherapy

References

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