Breast cancer, ER-positive - 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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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 ER+ breast cancer page for current regimens.
Last updated on 2024-07-23:18 regimens on this page
24 variants on this page
 
=Adjuvant therapy=
==ACT==
ACT: Adriamycin (Doxorubicin), Cyclophosphamide, Tamoxifen
===Regimen variant #1, 40/500/20===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Shien et al. 2014 (JCOG9401)	1994-1999 	Phase 3 (E-esc) 	Tamoxifen 	Did not meet primary endpoint of OSOS60: 85% vs 76.9%(HR 0.58, 95% CI 0.24-1.39)
Shien et al. 2014 (JCOG9404)	1994-1999 	Phase 3 (E-de-esc)	TUFT 	Did not meet primary endpoint of OS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Doxorubicin (Adriamycin) as follows:
**Cycles 1 to 6: 40 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) as follows:
**Cycles 1 to 6: 500 mg/m2 IV once on day 1
====Endocrine therapy====
*Tamoxifen (Nolvadex) 20 mg PO once per day on days 1 to 28
28-day cycle for 26 cycles (2 years)
===Regimen variant #2, 60/600/20===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fisher et al. 1990 (NSABP B-16)	1985-1988 	Phase 3 (E-esc)	1. PFT 	Not reported
Fisher et al. 1990 (NSABP B-16)	1985-1988 	Phase 3 (E-esc)	2. Tamoxifen	Seems to have longer OS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Doxorubicin (Adriamycin) as follows:
**Cycles 1 to 4: 60 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) as follows:
**Cycles 1 to 4: 600 mg/m2 IV once on day 1
====Endocrine therapy====
*Tamoxifen (Nolvadex) 10 mg PO twice per day on days 1 to 21
21-day cycle for 87 cycles (5 years)
===References===
# 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 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
# JCOG9401: Shien T, Iwata H, Aogi K, Fukutomi T, Inoue K, Kinoshita T, Takahashi M, Matsui A, Shibata T, Fukuda H. Tamoxifen versus tamoxifen plus doxorubicin and cyclophosphamide as adjuvant therapy for node-positive postmenopausal breast cancer: results of a Japan Clinical Oncology Group Study (JCOG9401). Int J Clin Oncol. 2014 Dec;19(6):982-8. Epub 2014 Jan 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# JCOG9404: Shien T, Iwata H, Fukutomi T, Inoue K, Aogi K, Kinoshita T, Ando J, Takashima S, Nakamura K, Shibata T, Fukuda H. Tamoxifen plus tegafur-uracil (TUFT) versus tamoxifen plus Adriamycin (doxorubicin) and cyclophosphamide (ACT) as adjuvant therapy to treat node-positive premenopausal breast cancer (PreMBC): results of Japan Clinical Oncology Group Study 9404. Cancer Chemother Pharmacol. 2014 Sep;74(3):603-9. Epub 2014 Jul 24. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
==Bilateral oophorectomy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Ahmann et al. 1977 	Not reported 	Randomized (C)	CFP & Oophorectomy 	Seems to have shorter PFS
Taylor et al. 1998 (SWOG S8692)	1987-08-01 to 1995-07-15	Randomized (C)	Goserelin 	Inconclusive whether equivalent FFS/OS (co-primary endpoints)
Love et al. 2016 (OSU-0476) 	2004-2011 	Phase 3 (C) 	Mid-luteal phase oophorectomy	Did not meet primary endpoint of OS
====Preceding treatment====
*Surgery
====Endocrine therapy====
*Bilateral oophorectomy
====Subsequent treatment====
*OSU-0476: Adjuvant tamoxifen
===References===
# 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 EuroPMC
#SWOG S8692: Taylor CW, Green S, Dalton WS, Martino S, Rector D, Ingle JN, Robert NJ, Budd GT, Paradelo JC, Natale RB, Bearden JD, Mailliard JA, Osborne CK. Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study. J Clin Oncol. 1998 Mar;16(3):994-9. link to original article EuroPMC
# OSU-0476: Love RR, Hossain SM, Hussain MM, Mostafa MG, Laudico AV, Siguan SS, Adebamowo C, Sun JZ, Fei F, Shao ZM, Liu Y, Akram Hussain SM, Zhang B, Cheng L, Panigaro S, Walta F, Chuan JH, Mirasol-Lumague MR, Yip CH, Navarro NS Jr, Huang CS, Lu YS, Ferdousy T, Salim R, Akhter C, Nahar S, Uy G, Young GS, Hade EM, Jarjoura D. Luteal versus follicular phase surgical oophorectomy plus tamoxifen in premenopausal women with metastatic hormone receptor-positive breast cancer. Eur J Cancer. 2016 Jun;60:107-16. Epub 2016 Apr 20. link to original article link to PMC article EuroPMC NCT00293540
==CFP & Bilateral oophorectomy==
CFP & Bilateral oophorectomy: Cyclophosphamide, Fluorouracil, Prednisone & Bilateral oophorectomy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ahmann et al. 1977	Not reported 	Randomized (E-esc)	Bilateral oophorectomy	Seems to have longer PFS
====Preceding treatment====
*Surgery, 3 weeks prior
====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) 30 mg PO once per day on days 1 to 7
*Bilateral oophorectomy
35-day cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==CMFT==
CMFT: Cyclophosphamide, Methotrexate, Fluorouracil, Tamoxifen
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Pritchard et al. 1996 (NCIC-CTG MA.4)	1984-1990 	Phase 3 (C)	Tamoxifen 	Did not meet endpoint of OS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Cyclophosphamide (Cytoxan) as follows:
**Cycles 1 to 8: 600 mg/m2 IV once on day 1
*Methotrexate (MTX) as follows:
**Cycles 1 to 8: 40 mg/m2 IV once on day 1
*Fluorouracil (5-FU) as follows:
**Cycles 1 to 8: 600 mg/m2 IV once on day 1
====Endocrine therapy====
*Tamoxifen (Nolvadex) 30 mg PO once per day on days 1 to 21
21-day cycle for 35 cycles (2 years)
===References===
# NCIC-CTG MA.4: Pritchard KI, Paterson AH, Paul NA, Zee B, Fine S, Pater J; National Cancer Institute of Canada Clinical Trials Group. Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. J Clin Oncol. 1996 Oct;14(10):2731-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Pritchard KI, Paterson AH, Fine S, Paul NA, Zee B, Shepherd LE, Abu-Zahra H, Ragaz J, Knowling M, Levine MN, Verma S, Perrault D, Walde PL, Bramwell VH, Poljicak M, Boyd N, Warr D, Norris BD, Bowman D, Armitage GR, Weizel H, Buckman RA; NCIC-CTG. Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1997 Jun;15(6):2302-11. link to original article EuroPMC
==PFT==
PFT: Phenylalanine mustard (Melphalan), 5-Fluorouracil, Tamoxifen
===Regimen variant #1, 2 years of tamoxifen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Fisher et al. 1981 (NSABP B-09)	1977-1980 	Phase 3 (E-RT-esc)	PF 	Longer RFS
====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
====Endocrine therapy====
*Tamoxifen (Nolvadex) 10 mg PO twice per day on days 1 to 42
42-day cycle for 17 cycles (2 years)
===Regimen variant #2, 5 years of tamoxifen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fisher et al. 1990 (NSABP B-16)	1985-1988 	Phase 3 (E-esc)	1. ACT 	Not reported
Fisher et al. 1990 (NSABP B-16)	1985-1988 	Phase 3 (E-esc)	2. Tamoxifen	Seems to have longer DDFS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Melphalan (Alkeran) as follows:
**Cycles 1 to 17: 4 mg/m2 PO once per day on days 1 to 5
*Fluorouracil (5-FU) as follows:
**Cycles 1 to 17: 300 mg/m2 IV once per day on days 1 to 5
====Endocrine therapy====
*Tamoxifen (Nolvadex) 10 mg PO twice per day on days 1 to 42
42-day cycle for 43 cycles (5 years)
===References===
# 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 dosing details in manuscript have been reviewed by our editors 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-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 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
==PT==
PT: Prednisone & Tamoxifen
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Goldhirsch et al. 1984 (LBCS III)	1978-1981 	Phase 3 (E-esc)	1. CMFPT 	Seems to have shorter DFS
Goldhirsch et al. 1984 (LBCS III)	1978-1981 	Phase 3 (E-esc)	2. Observation	Longer DFS
Goldhirsch et al. 1984 (LBCS IV) 	1978-1981 	Phase 3 (E-esc)	Observation 	Seems to have longer DFS
====Preceding treatment====
*Mastectomy
====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 13 cycles (12 months)
===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 dosing details in manuscript have been reviewed by our editors EuroPMC
=Metastatic disease, all lines of therapy=
==Aminoglutethimide monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Smith et al. 1978 	1977-1978 	Non-randomized 	 	
Santen et al. 1981 	Not reported 	Randomized (E-switch-ic)	Bilateral adrenalectomy 	Did not meet primary endpoint of ORR
Stuart-Harris et al. 1984 	Not reported 	Phase 2 	 	
Canney et al. 1988 	Not reported 	Phase 3 (E-switch-ic) 	MPA 	Did not meet primary endpoint of ORR
Lundgren et al. 1989 	Not reported 	Phase 3 (E-switch-ic) 	Megestrol 	Did not meet primary endpoint of ORR
Garcia-Giralt et al. 1992 	Not reported 	Phase 3 (E-switch-ic) 	MPA 	Seems to have longer TTP
Robustelli della Cuna et al. 1993	Not reported 	Phase 3 (E-de-esc) 	Aminoglutethimide; higher-dose 	Did not meet primary endpoint of ORR
Gale et al. 1994 	1977 to not reported	Phase 3 (E-switch-ic) 	1. Tamoxifen2. Bilateral adrenalectomy	Did not meet co-primary endpoints of DOR/TTF/OS
Gershanovich et al. 1998 (AR/BC3)	Not reported 	Randomized (C) 	1. Letrozole; 0.5 mg/day 	Did not meet primary endpoint of ORR
Gershanovich et al. 1998 (AR/BC3)	Not reported 	Randomized (C) 	2. Letrozole; 2.5 mg/day 	Might have lower ORR
====Endocrine therapy====
*Aminoglutethimide (Cytadren) 250 mg PO twice per day
====Supportive therapy====
*Hydrocortisone (Cortef) 37.5 mg/day PO
Continued indefinitely
===References===
# Smith IE, Fitzharris BM, McKinna JA, Fahmy DR, Nash AG, Neville AM, Gazet JC, Ford HT, Powles TJ. Aminoglutethimide in treatment of metastatic breast carcinoma. Lancet. 1978 Sep 23;2(8091):646-9. link to original article EuroPMC
# 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 EuroPMC
# Stuart-Harris R, Dowsett M, Bozek T, McKinna JA, Gazet JC, Jeffcoate SL, Kurkure A, Carr L, Smith IE. Low-dose aminoglutethimide in treatment of advanced breast cancer. Lancet. 1984 Sep 15;2(8403):604-7. link to original article EuroPMC
# Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, Spooner D. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. J Natl Cancer Inst. 1988 Sep 21;80(14):1147-51. link to original article EuroPMC
# Lundgren S, Gundersen S, Klepp R, Lønning PE, Lund E, Kvinnsland S. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Res Treat. 1989 Nov;14(2):201-6. link to original article EuroPMC
# Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P, Fumoleau P, Gorins A, Guerin D, Guerin R, Maillart P, Mauriac L, May-Levin F, Metz R, Namer M, Olivier JP, Pommatau E, Pouillart P, Pujade-Lauraine E, Rouesse J, Serrou B, Vitse M, Zylberait D. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Res Treat. 1992;24(2):139-45. link to original article EuroPMC
# Robustelli della Cuna G, Pannuti F, Martoni A, Camaggi CM, Strocchi E, Da Prada GA, Tanneberger S; Italian Cooperative Group. Aminoglutethimide in advanced breast cancer: prospective, randomized comparison of two dose levels. Anticancer Res. 1993 Nov-Dec;13(6B):2367-71. dosing details in abstract have been reviewed by our editors EuroPMC
# Gale KE, Andersen JW, Tormey DC, Mansour EG, Davis TE, Horton J, Wolter JM, Smith TJ, Cummings FJ; ECOG. Hormonal treatment for metastatic breast cancer: an Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen. Cancer. 1994 Jan 15;73(2):354-61. link to original article EuroPMC
# AR/BC3: Gershanovich M, Chaudri HA, Campos D, Lurie H, Bonaventura A, Jeffrey M, Buzzi F, Bodrogi I, Ludwig H, Reichardt P, O'Higgins N, Romieu G, Friederich P, Lassus M; Letrozole International Trial Group. Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Ann Oncol. 1998 Jun;9(6):639-45. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Bilateral oophorectomy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Ingle et al. 1986a 	1978-1984 	Phase 3 (C) 	Tamoxifen 	Did not meet endpoints
Buchanan et al. 1986	1979-1983 	Phase 3 (C) 	Tamoxifen 	Might have shorter PFS
Crump et al. 1997 	Not reported 	Randomized (C)	Tamoxifen 	Did not meet pooled endpoint of ORR
Note: while Crump et al. 1997 is a meta-analysis, it is also the primary report for a randomized trial used to support registration of this drug.
====Endocrine therapy====
*Bilateral oophorectomy
===References===
# Ingle JN, Krook JE, Green SJ, Kubista TP, Everson LK, Ahmann DL, Chang MN, Bisel HF, Windschitl HE, Twito DI, Pfeifle DM. Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastatic breast cancer. J Clin Oncol. 1986 Feb;4(2):178-85. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Buchanan RB, Blamey RW, Durrant KR, Howell A, Paterson AG, Preece PE, Smith DC, Williams CJ, Wilson RG. A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer. J Clin Oncol. 1986 Sep;4(9):1326-30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Crump M, Sawka CA, DeBoer G, Buchanan RB, Ingle JN, Forbes J, Meakin JW, Shelley W, Pritchard KI. An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer. Breast Cancer Res Treat. 1997 Jul;44(3):201-10. link to original article EuroPMC
==CAF & MPA==
CAF & MPA: Cyclophosphamide, Adriamycin (Doxorubicin), Fluorouracil, MedroxyProgesterone Acetate
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Tominaga et al. 1994	Not reported 	Phase 3 (E-esc)	CAF 	Seems to have higher ORR
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 100 mg PO once per day on days 1 to 14
*Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 1 & 8
*Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
====Endocrine therapy====
*Medroxyprogesterone acetate (MPA) 1200 mg PO once per day on days 1 to 28
28-day cycle for 3 cycles
===References===
# Tominaga T, Abe O, Ohshima A, Hayasaka H, Uchino J, Abe R, Enomoto K, Izuo M, Watanabe H, Takatani O, Yoshida M, Sakai K, Koyama H, Hattori T, Senoo T, Monden Y, Nomura Y. Comparison of chemotherapy with or without medroxyprogesterone acetate for advanced or recurrent breast cancer. Eur J Cancer. 1994;30A(7):959-64. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==DES monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Kennedy 1965 	Not reported in abstract	Randomized (E-switch-ic)	Testosterone 	Not available
Carter et al. 1977	Not reported 	Phase 3 (E-switch-ic) 	DES; other dosings 	See paper
Kiang et al. 1981 	1975-1982 	Randomized (C) 	Cyclophosphamide, 5-FU, DES	Seems to have shorter OS1
Ingle et al. 1981 	1977-1980 	Phase 3 (C) 	Tamoxifen 	Did not meet primary endpoint of ORR
1Reported efficacy for Kiang et al. 1981 is based on the 1985 update.
Note: The full manuscript for Kennedy 1965 was not available for review.
====Endocrine therapy====
*Diethylstilbestrol (DES) 5 mg PO three times per day
Continued indefinitely
===References===
# Kennedy BJ. Diethylstilbestrol versus testosterone propionate therapy in advanced breast cancer. Surg Gynecol Obstet. 1965 Jun;120:1246-50. EuroPMC
# Carter AC, Sedransk N, Kelley RM, Ansfield FJ, Ravdin RG, Talley RW, Potter NR; Cooperative Breast Cancer Group. Diethylstilbestrol: recommended dosages for different categories of breast cancer patients: report of the Cooperative Breast Cancer Group. JAMA. 1977 May 9;237(19):2079-8. link to original article EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
==Estradiol monotherapy==
===Regimen variant #1, 6 mg/day===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ellis et al. 2009 (WU 04-0412)	2004-2008 	Randomized Phase 2 (E-de-esc)	Estradiol; 30 mg/day	Did not meet primary endpoint of CBR
====Endocrine therapy====
*Estradiol 6 mg PO once per day
Continued indefinitely
===Regimen variant #2, 30 mg/day===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ellis et al. 2009 (WU 04-0412)	2004-2008 	Randomized Phase 2 (C)	Estradiol; 6 mg/day	Did not meet primary endpoint of CBR
====Endocrine therapy====
*Estradiol 30 mg PO once per day
Continued indefinitely
===References===
# WU 04-0412: Ellis MJ, Gao F, Dehdashti F, Jeffe DB, Marcom PK, Carey LA, Dickler MN, Silverman P, Fleming GF, Kommareddy A, Jamalabadi-Majidi S, Crowder R, Siegel BA. Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study. JAMA. 2009 Aug 19;302(7):774-80. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT00324259
==Fluoxymesterone monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Kennedy 1958	Not reported 	Non-randomized
====Endocrine therapy====
*Fluoxymesterone (Halotestin) 20 or 40 mg PO once per day
Continued indefinitely
===References===
# Kennedy BJ. Fluoxymesterone therapy in advanced breast cancer. N Engl J Med. 1958 Oct 2;259(14):673-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Fluoxymesterone & Tamoxifen==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Ingle et al. 1988	1981-1985 	Phase 3 (E-esc)	Tamoxifen 	Seems to have longer TTP1
1Reported efficacy is based on the 1991 update.
====Endocrine therapy====
*Fluoxymesterone (Halotestin) 10 mg PO twice per day
*Tamoxifen (Nolvadex) 10 mg PO twice per day
Continued indefinitely
===References===
# Ingle JN, Twito DI, Schaid DJ, Cullinan SA, Krook JE, Mailliard JA, Marschke RF, Long HJ, Gerstner JG, Windschitl HE, Everson LK, Pfeifle DM. Randomized clinical trial of tamoxifen alone or combined with fluoxymesterone in postmenopausal women with metastatic breast cancer. J Clin Oncol. 1988 May;6(5):825-31. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
## Update: Ingle JN, Twito DI, Schaid DJ, Cullinan SA, Krook JE, Mailliard JA, Tschetter LK, Long HJ, Gerstner JG, Windschitl HE, Levitt R, Pfeifle DM. Combination hormonal therapy with tamoxifen plus fluoxymesterone versus tamoxifen alone in postmenopausal women with metastatic breast cancer: an updated analysis. Cancer. 1991 Feb 15;67(4):886-91. link to original article EuroPMC
==Formestane monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Coombes et al. 1984 	Not reported 	Pilot 	 	
Thürlimann et al. 1997 (SAKK 20/90)	1991-1995 	Phase 3 (E-switch-ic)	Megestrol 	Did not meet primary endpoint of TTF
====Endocrine therapy====
*Formestane (Lentaron) 250 mg IM once on day 1
14-day cycles
===References===
# Coombes RC, Goss P, Dowsett M, Gazet JC, Brodie A. 4-Hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. Lancet. 1984 Dec 1;2(8414):1237-9. link to original article EuroPMC
# SAKK 20/90: Thürlimann B, Castiglione M, Hsu-Schmitz SF, Cavalli F, Bonnefoi H, Fey MF, Morant R, Löhnert T, Goldhirsch A; Swiss Group for Clinical Cancer Research. Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Eur J Cancer. 1997 Jun;33(7):1017-24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Medroxyprogesterone acetate monotherapy==
===Regimen variant #1, 500 mg/day===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cuna et al. 1978 	Not reported 	Phase 3 (E-de-esc)	MPA; 1000 mg/day 	Did not meet primary endpoint of ORR
Pannuti et al. 1979 (UICC 75-09)	Not reported 	Randomized (C) 	MPA; 1500 mg/day 	Did not meet primary endpoint of ORR
Canney et al. 1988 	Not reported 	Phase 3 (C) 	Aminoglutethimide	Did not meet primary endpoint of ORR
Byrne et al. 1997 (ANZ8613) 	1987-1993 	Phase 3 (C) 	MPA & Tamoxifen 	Did not meet primary endpoint of TTP
Note: Canney et al. 1988 does not have dosing information in the abstract.
====Endocrine therapy====
*Medroxyprogesterone acetate (MPA) 500 mg PO once per day
Continued indefinitely
===Regimen variant #2, 900 mg/day===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
van Veelen et al. 1986	1980-1984 	Phase 3 (E-switch-ic)	Tamoxifen 	Did not meet primary endpoint of ORR
====Endocrine therapy====
*Medroxyprogesterone acetate (MPA) 300 mg PO three times per day
Continued indefinitely
===Regimen variant #3, 1000 mg/day (high-dose)===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cavalli et al. 1984 	1979-1982 	Phase 3 (E-esc) 	MPA; low-dose 	Higher ORR
Garcia-Giralt et al. 1992 	Not reported 	Phase 3 (C) 	Aminoglutethimide	Seems to have shorter TTP
Castiglione-Gertsch et al. 1993	1982-1985 	Phase 3 (E-switch-ic)	Tamoxifen 	Might have longer TTP
Muss et al. 1994 	1985-1990 	Phase 3 (E-switch-ic)	Tamoxifen 	Might have longer OS
====Endocrine therapy====
*Medroxyprogesterone acetate (MPA) 1000 mg PO or IM once per day or 500 mg PO twice per day
Continued indefinitely
===Regimen variant #4, 1200 mg/day (high-dose)===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Izuo et al. 1985	1981-1983 	Phase 3 (E-switch-ic)	Mepitiostane	Did not meet primary endpoint of ORR
====Endocrine therapy====
*Medroxyprogesterone acetate (MPA) 400 mg PO three times per day
Continued indefinitely
===References===
# Cuna GR, Calciati A, Strada MR, Bumma C, Campio L. High dose medroxyprogesterone acetate (MPA) treatment in metastatic carcinoma of the breast: a dose-response evaluation. Tumori. 1978 Apr 30;64(2):143-9. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# UICC 75-09: Pannuti F, Martoni A, Di Marco AR, Piana E, Saccani F, Becchi G, Mattioli G, Barbanti F, Marra GA, Persiani W, Cacciari L, Spagnolo F, Palenzona D, Rocchetta G. Prospective, randomized clinical trial of two different high dosages of medroxyprogesterone acetate (MAP) in the treatment of metastatic breast cancer. Eur J Cancer. 1979 Apr;15(4):593-601. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Cavalli F, Goldhirsch A, Jungi F, Martz G, Mermillod B, Alberto P. Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer. J Clin Oncol. 1984 May;2(5):414-9. link to original article EuroPMC
# Izuo M, Yoshida M, Tominaga T, Abe O, Enomoto K, Nomura Y, Kubo K, Takatani O. A phase III trial of oral high-dose medroxyprogesterone acetate (MPA) versus mepitiostane in advanced postmenopausal breast cancer. Cancer. 1985 Dec 1;56(11):2576-9. link to original article EuroPMC
# van Veelen H, Willemse PH, Tjabbes T, Schweitzer MJ, Sleijfer DT. Oral high-dose medroxyprogesterone acetate versus tamoxifen: a randomized crossover trial in postmenopausal patients with advanced breast cancer. Cancer. 1986 Jul 1;58(1):7-13. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, Spooner D. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. J Natl Cancer Inst. 1988 Sep 21;80(14):1147-51. link to original article EuroPMC
# Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P, Fumoleau P, Gorins A, Guerin D, Guerin R, Maillart P, Mauriac L, May-Levin F, Metz R, Namer M, Olivier JP, Pommatau E, Pouillart P, Pujade-Lauraine E, Rouesse J, Serrou B, Vitse M, Zylberait D. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Res Treat. 1992;24(2):139-45. link to original article EuroPMC
# Castiglione-Gertsch M, Pampallona S, Varini M, Cavalli F, Brunner K, Senn HJ, Goldhirsch A, Metzger U. Primary endocrine therapy for advanced breast cancer: to start with tamoxifen or with medroxyprogesterone acetate?. Ann Oncol. 1993 Nov;4(9):735-40. link to original article EuroPMC
# Muss HB, Case LD, Atkins JN, Bearden JD 3rd, Cooper MR, Cruz JM, Jackson DV Jr, O'Rourke MA, Pavy MD, Powell BL, Richards F, Spurr CL, Eagle K, White DR; Piedmont Oncology Association. Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study. J Clin Oncol. 1994 Aug;12(8):1630-8. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# ANZ8613: Byrne MJ, Gebski V, Forbes J, Tattersall MH, Simes RJ, Coates AS, Dewar J, Lunn M, Flower C, Gill PG, Stewart J; Australian-New Zealand Breast Cancer Trials Group. Medroxyprogesterone acetate addition or substitution for tamoxifen in advanced tamoxifen-resistant breast cancer: a phase III randomized trial. J Clin Oncol. 1997 Sep;15(9):3141-8. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Megestrol monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Muss et al. 1988 	1981-1984 	Phase 3 (E-switch-ic)	Tamoxifen 	Did not meet primary endpoint of ORR
Lundgren et al. 1989 	Not reported 	Phase 3 (C) 	Aminoglutethimide 	Did not meet primary endpoint of ORR
Gill et al. 1993 	1984-1989 	Phase 3 (E-switch-ic)	1. Tamoxifen2. Megestrol & Tamoxifen 	Did not meet endpoint of ORR
Buzdar et al. 1996 	Not reported 	Phase 3 (C) 	Anastrozole 	Seems to have shorter OS1
Russell et al. 1997 (SWOG S8312) 	1984-1990 	Phase 3 (C) 	Aminoglutethimide, Hydrocortisone, Megestrol 	Did not meet primary endpoint of OS
Muss et al. 1990 	1985-1988 	Phase 3 (C) 	Megestrol; higher-dose 	Seems to have shorter OS
Stuart et al. 1996 	1985-1988 	Phase 3 (E-switch-ic)	Tamoxifen 	Did not meet endpoint of OS
Abrams et al. 1999 (CALGB 8741) 	1987-1991 	Phase 3 (C) 	Megestrol; higher-dose 	Did not meet primary endpoint of ORR
Buzdar et al. 1996 (Protocol 03) 	1989-1991 	Phase 3 (C) 	Fadrozole 	Did not meet primary endpoint of ORR
Buzdar et al. 1996 (Protocol 06) 	1989-1991 	Phase 3 (C) 	Fadrozole 	Did not meet primary endpoint of ORR
Thürlimann et al. 1997 (SAKK 20/90)	1991-1995 	Phase 3 (C) 	Formestane 	Did not meet primary endpoint of TTF
Goss et al. 1999 	1991-1995 	Phase 3 (C) 	Vorozole 	Did not meet primary endpoint of ORR
Jonat et al. 1996 	1993-03 to 1994-09 	Phase 3 (C) 	1. Anastrozole; 1 mg/day 	Seems to have shorter OS1
Jonat et al. 1996 	1993-03 to 1994-09 	Phase 3 (C) 	2. Anastrozole; 10 mg/day 	Did not meet endpoint of OS
Dombernowsky et al. 1998 (AR/BC2) 	1993-03 to 1994-09 	Randomized (C) 	1. Letrozole; 0.5 mg/day 	Not reported
Dombernowsky et al. 1998 (AR/BC2) 	1993-03 to 1994-09 	Randomized (C) 	2. Letrozole; 2.5 mg/day 	Seems to have shorter OS
Kaufmann et al. 2000 	1995-1998 	Phase 3 (C) 	Exemestane 	Inconclusive whether equivalent ORR (primary endpoint)Seems to have shorter OS
Buzdar et al. 2001 	Not reported 	Phase 3 (C) 	1. Letrozole; 0.5 mg/day2. Letrozole; 2.5 mg/day	Did not meet primary endpoint of ORR
1Reported efficacy for Jonat et al. 1996 & Buzdar et al. 1996 is based on the 1998 pooled update.
====Endocrine therapy====
*Megestrol (Megace) 160 mg PO once per day or 40 mg PO four times per day
Continued indefinitely
===References===
# Muss HB, Wells HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, Powell BL, Richards F, White DR, Zekan PJ, Spurr CL, Pope E, Case D, Morgan TM; Piedmont Oncology Association. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1988 Jul;6(7):1098-106. link to original article EuroPMC
# Lundgren S, Gundersen S, Klepp R, Lønning PE, Lund E, Kvinnsland S. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Res Treat. 1989 Nov;14(2):201-6. link to original article EuroPMC
# Muss HB, Case LD, Capizzi RL, Cooper MR, Cruz J, Jackson D, Richards F 2nd, Powell BL, Spurr CL, White D, Zekan P, Read S, Cates-Wilkie S, Bearden J, McCullough J, Callahan R, Karb K, Atkins J, Paschal B, Ramseur B, Lusk J, Stanley V; Piedmont Oncology Association. High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1990 Nov;8(11):1797-805. link to original article EuroPMC
# Gill PG, Gebski V, Snyder R, Burns I, Levi J, Byrne M, Coates A. Randomized comparison of the effects of tamoxifen, megestrol acetate, or tamoxifen plus megestrol acetate on treatment response and survival in patients with metastatic breast cancer. Ann Oncol. 1993 Nov;4(9):741-4. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Jonat W, Howell A, Blomqvist C, Eiermann W, Winblad G, Tyrrell C, Mauriac L, Roche H, Lundgren S, Hellmund R, Azab M. A randomised trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer. Eur J Cancer. 1996 Mar;32A(3):404-12. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
## Pooled update: Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. link to original article EuroPMC
## Pooled update: Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. link to original article EuroPMC
#Protocol 03: Buzdar AU, Smith R, Vogel C, Bonomi P, Keller AM, Favis G, Mulagha M, Cooper J. Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: results of two randomized double blind controlled multiinstitutional trials. Cancer. 1996 Jun 15;77(12):2503-13. link to original article EuroPMC
#Protocol 06: Buzdar AU, Smith R, Vogel C, Bonomi P, Keller AM, Favis G, Mulagha M, Cooper J. Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: results of two randomized double blind controlled multiinstitutional trials. Cancer. 1996 Jun 15;77(12):2503-13. link to original article EuroPMC
# Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. link to original article EuroPMC
## Update: Buzdar AU, Jones SE, Vogel CL, Wolter J, Plourde P, Webster A; Arimidex Study Group. A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Cancer. 1997 Feb 15;79(4):730-9. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
## Pooled update: Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. link to original article EuroPMC
# Stuart NS, Warwick J, Blackledge GR, Spooner D, Keen C, Taylor AR, Tyrell C, Webster DJ, Earl H. A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer. Eur J Cancer. 1996 Oct;32A(11):1888-92. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# SAKK 20/90: Thürlimann B, Castiglione M, Hsu-Schmitz SF, Cavalli F, Bonnefoi H, Fey MF, Morant R, Löhnert T, Goldhirsch A; Swiss Group for Clinical Cancer Research. Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Eur J Cancer. 1997 Jun;33(7):1017-24. link to original article EuroPMC
# SWOG S8312: Russell CA, Green SJ, O'Sullivan J, Hynes HE, Budd GT, Congdon JE, Martino S, Osborne CK. Megestrol acetate and aminoglutethimide/hydrocortisone in sequence or in combination as second-line endocrine therapy of estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group phase III trial. J Clin Oncol. 1997 Jul;15(7):2494-501. link to original article EuroPMC
# AR/BC2: Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J, Bezwoda W, Gardin G, Gudgeon A, Morgan M, Fornasiero A, Hoffmann W, Michel J, Hatschek T, Tjabbes T, Chaudri HA, Hornberger U, Trunet PF. Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol. 1998 Feb;16(2):453-61. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Goss PE, Winer EP, Tannock IF, Schwartz LH; North American Vorozole Study Group. Randomized phase III trial comparing the new potent and selective third-generation aromatase inhibitor vorozole with megestrol acetate in postmenopausal advanced breast cancer patients. J Clin Oncol. 1999 Jan;17(1):52-63. link to original article EuroPMC
# 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 dosing details in abstract have been reviewed by our editors EuroPMC
# Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Zilembo N, Dugardyn JL, Nasurdi C, Mennel RG, Cervek J, Fowst C, Polli A, di Salle E, Arkhipov A, Piscitelli G, Miller LL, Massimini G; Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. J Clin Oncol. 2000 Apr;18(7):1399-411. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Buzdar A, Douma J, Davidson N, Elledge R, Morgan M, Smith R, Porter L, Nabholtz J, Xiang X, Brady C. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol. 2001 Jul 15;19(14):3357-66. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==TAD (Tamoxifen)==
TAD: Tamoxifen, Aminoglutethimide, Danazol
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Powles et al. 1984	1979-1983 	Phase 3 (E-esc)	Tamoxifen 	Seems to have higher ORR
Note: this patient population was not selected by hormone receptor status.
====Endocrine therapy====
*Tamoxifen (Nolvadex) 10 mg PO twice per day
*Aminoglutethimide (Cytadren) 250 mg PO three times per day
*Danazol (Danocrine) 100 mg PO three times per day
====Supportive therapy====
*Hydrocortisone (Cortef) 20 mg PO twice per day
Continued indefinitely
===References===
# Powles TJ, Ashley S, Ford HT, Gazet JC, Nash AG, Neville AM, Coombes RC. Treatment of disseminated breast cancer with tamoxifen, aminoglutethimide, hydrocortisone, and danazol, used in combination or sequentially. Lancet. 1984 Jun 23;1(8391):1369-73. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Metastatic disease, subsequent lines of therapy=
==Fluoxymesterone & Tamoxifen==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Tormey et al. 1983	Not reported 	Randomized (E-esc)	Tamoxifen 	Longer TTTF
====Endocrine therapy====
*Fluoxymesterone (Halotestin) 7 mg/m2 PO twice per day
*Tamoxifen (Nolvadex) across a range of doses PO
Continued indefinitely
===References===
# Tormey DC, Lippman ME, Edwards BK, Cassidy JG. Evaluation of tamoxifen doses with and without fluoxymesterone in advanced breast cancer. Ann Intern Med. 1983 Feb;98(2):139-44. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
Category:Breast cancer regimens
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Category:Malignant breast neoplasm