Chemoregimen - Breast Cancer

Breast Cancer

Adjuvant therapy
Hormonal therapy
Chemotherapy
Targeted therapy

Metastatic breast cancer
Hormonal therapy
Chemotherapy
Targeted therapy

Adjuvant therapy

Hormonal therapy

Tamoxifen
Tamoxifen 20 mg po qd x 5 years

Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of randomized trials. Lancet 2005; 365:1687 (link to the article).

Tamoxifen + Goserelin
Tamoxifen 20 mg po qd
Goserelin (Zoladex) 3.6 mg sc qm
for 3-5 years

Gnant M et al. Adjuvant ovarian suppression combined with tamoxifen or anastrozole, alone or in combination with zoledronic acid, in premenopausal women with endocrine-responsive, stage I and II breast cancer: first efficiency results from ABCSG-12. 2008 ASCO annual meeting. Abstract LBA4 (link to the abstract).

LHRH-agonists in Early Breast Cancer Overview Group. Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet 2007; 369:1711 (link to the article).

Tamoxifen + Goserelin + Zoledronic acid
Tamoxifen 20 mg po qd
Goserelin (Zoladex) 3.6 mg sc qm
Zoledronic acid (Zometa) 4 mg iv q6m
for 3 years

Anastrozole
Anastrozole (Arimidex) 1 mg po qd x 5 years or x 2-3 years after 3-2 years of tamoxifen

The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trialists' Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 2008; 9:45 (link to the article).

Kaufmann M et al. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: The ARNO 95 study. J Clin Oncol 2007; 25:2664 (link to the article).

Howell A et al. Results of ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 2005; 365:60 (link to the article).

Anastrozole + Goserelin
Anastrozole (Arimidex) 1 mg po qd
Goserelin (Zoladex) 3.6 mg sc qm
for 3 years

Anastrozole + Goserelin + Zoledronic acid
Anastrozole (Arimidex) 1 mg po qd
Goserelin (Zoladex) 3.6 mg sc qm
Zoledronic acid (Zometa) 4 mg iv q6m
for 3 years

Letrozole
Letrozole (Femara) 2.5 mg po qd x 5 years upfront or following 5 years of tamoxifen

Crivellari D et al. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: The BIG 1-98 Trial. J Clin Oncol 2008; 26:1972 (link to the article).

Goss PE et al. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol 2008; 26:1948 (link to the article).

Hyman B et al. Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG Intergroup Trial MA.17. J Clin Oncol 2008; 26:1956 (link to the article).

Rasmussen BB et al. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplemental results from the BIG 1-98 randomized trial. Lancet Oncol 2008; 9:23 (link to the article).

Coates AS et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol 2007; 25:486 (link to the article).

Goss PE et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early stage breast cancer. N Eng J Med 2003; 349:1793 (link to the article).

Exemestane
Exemestane (Aromasin) 25 mg po qd x 2-3 years after 3-2 years of tamoxifen or 5 years after 5 years of tamoxifen

Mamounas EP et al. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intent-to-treat analysis of National Surgical Adjuvant Breast and Bowel Project B-33 Trial. J Clin Oncol 2008; 26:1965 (link to the article).

Coombes RC et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 2007; 369:559 (link to the article).

Coombes RC et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Eng J Med 2004; 350:1081 (link to the article).

Chemotherapy (back to top)

AC
Doxorubicin (Adriamycin) 60 mg/m2 iv d1
Cyclophosphamide ((Cytoxan) 600 mg/m2 iv d1
Q3w x 4 cycles

Muss HB et al. Standard chemotherapy (CMF or AC) versus capecitabine in early-stage breast cancer (BC) patients agec 65 or older: results of CALGB/CTSU 49907. 2008 ASCO annual meeting. Abstract 507 (link to the abstract).

Fisher, B et al. Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials. J Natl Cancer Inst 2004; 96:1823 (link to the article).

TC
Docetaxel (Taxotere) 75 mg/m2 iv over 30-60 min d1
Cyclophosphamide (Cytoxan) 600 mg/m2 iv over 30-60 min d1
Q3w x 4 cycles

Jones SE et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 2006; 24:5381 (link to the article).

CMF PO
Cyclophosphamide (Cytoxan) 100 mg/m2/d po d1-14
Methotrexate (MTX) 40 mg/m2 iv d1 and 8
5-FU 600 mg/m2 iv d1 and 8
Q4w x 6 cycles

Poole CJ et al. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Eng J Med 2006; 355:1851 (link to the article).

Hutchins LF et al. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of intergroup protocol INT-0102. J Clin Oncol 2005; 23:8313 (link to the article).

Bonadonna G et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Eng J Med 1976; 294:405 (link to the article).

CMF IV
Cyclophosphamide (Cytoxan) 600 mg/m2 iv d1
Methotrexate (MTX) 40 mg/m2 iv d1
5-FU 600 mg/m2 iv d1
Q3w x 6 cycles

Weiss RB et al. Adjuvant chemotherapy after conservative surgery plus irradiation versus modified radical mastectomy. Analysis of drug dosing and toxicity. Am J Med 1987; 83:455 (link to the article).

Epirubicin→CMF
Epirubicin 100 mg/m2 iv q3w x 4 cycles
Followed by CMF x 4 cycles

Poole CJ et al. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Eng J Med 2006; 355:1851 (link to the article).

CAF
Regimen 1 po
Cyclophosphamide (Cytoxan) 100 mg/m2/d po d1-14
Doxorubicin (Adriamycin) 30 mg/m2 iv d1, 8
5-FU 500 mg/m2 iv d1, 8
Q4w x 6 cycles

Regimen 2 iv
Cyclophosphamide (Cytoxan) 500 mg/m2 iv d1
Doxorubicin (Adriamycin) 50 mg/m2 iv d1
5-FU 500 mg/m2 iv d1
Q3w x 6 cycles

Martin M et al. Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen d1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen d1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group. Ann Oncol 2003; 14:833 (link to the article).

AC→Paclitaxel Q3w
Doxorubicin (Adriamycin) 60 mg/m2 iv push over 5-15 min d1
Cyclophosphamide (Cytoxan) 600 mg/m2 iv over 30-60 min d1
Q3w x 4 cycles
Followed by
Paclitaxel (Taxol) 175 mg/m2 iv over 3 hours
Q3w x 4 cycles

Sparano JA et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Eng J Med 2008; 358:1663 (link to the article).

Mamounas EP. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B28. J Clin Oncol 2005; 23:3686 (link to the article).

Henderson, IC et al. 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; 21:976 (link to the article).

AC→Paclitaxel Qw
Doxorubicin (Adriamycin) 60 mg/m2 iv push over 5-15 min d1
Cyclophosphamide (Cytoxan) 600 mg/m2 iv over 30-60 min d1
Q3w x 4 cycles
Followed by
Paclitaxel (Taxol) 80 mg/m2 iv over 1 hour
Qw x 12 cycles

Sparano JA et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Eng J Med 2008; 358:1663 (link to the article).

AC→Docetaxel Q3w
Doxorubicin (Adriamycin) 60 mg/m2 iv push over 5-15 min d1
Cyclophosphamide (Cytoxan) 600 mg/m2 iv over 30-60 min d1
Q3w x 4 cycles
Followed by
Docetaxel (Taxotere) 100 mg/m2 iv over 1 hour
Q3w x 4 cycles

Sparano JA et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Eng J Med 2008; 358:1663 (link to the article).

AT→T
Doxorubicin (Adriamycin) 50 mg/m2 iv d1
Paclitaxel (Taxol) 200 mg/m2 iv d1
Q3w x 4 cycles
Followed by
Paclitaxel (Taxol) 80 mg/m2 iv over 1 h qw x 12 weeks

Loesch DM et al. A randomized, multicenter phase III trial comparing doxorubicin + cyclophosphamide followed by paclitaxel or doxorubicin + paclitaxel followed by weekly paclitaxel as adjuvant therapy for high-risk breast cancer. 2007 ASCO annual meeting. Abstract 517 (link to the abstract).

Dose-dense AC→T
Doxorubicin (Adriamycin) 60 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 600 mg/m2 iv d1
Q2w x 4 cycles
Followed by
Paclitaxel (Taxol) 175 mg/m2 iv
Q2w x 4 cycles
Filgrastim (Neupogen) or pegfilgrastim (Neulasta) support

Burstein HJ et al. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol 2005; 23:8340 (link to the article).

Citron, ML et al. 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; 21:1431 (link to the article).

TAC
Docetaxel (Taxotere) 75 mg/m2 iv d1
Doxorubicin (Adriamycin) 50 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 500 mg/m2 iv d1
Q3w x 6 cycles
Filgrastim (Neupogen) support

Martin M et al. Adjuvant docetaxel for node-positive breast cancer. N Eng J Med 2005; 352:2302 (link to the article).

FEC→T
5-FU 500 mg/m2 iv d1
Epirubicin 100 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 500 mg/m2 iv d1
Q3w x 3 cycles
Followed by
Docetaxel (Taxotere) 100 mg/m2 iv
Q3w x 3 cycles

Roche H et al. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: The FNCLCC PACS 01 trial. J Clin Oncol 2006; 24:5664 (link to the article).

CEF
Cyclophosphamide (Cytoxan) 75 mg/m2 po qd d1-14
Epirubicin 60 mg/m2 iv d1 and 8
5-FU 500 mg/m2 iv d1 and 8
Q4w x 6 cycles

Levine MN et al. Randomized trial comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials Group Trial MA5. J Clin Oncol 2005; 23:5166 (link to the article).

Dose-dense EC→T
Epirubicin 120 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 830 mg/m2 iv d1
Q2w x 6 cycles
Paclitaxel (Taxol) 175 mg/m2 iv
Q3w x 4 cycles
Filgrastim (Neupogen) 5 mcg/kg sc d2-13
Epoetin alfa (Procrit) 40,000 units sc qw

Burnell M et al. A randomized trial of CEF versus dose dense EC followed by paclitaxel versus AC followed by paclitaxel in women with node positive or high risk node negative breast cancer, NCIC CTG MA.21: Results of an interim analysis. 2006 San Antonio Breast Cancer Symposium. Abstract 53 (link to the abstract).

Dose-dense Epirubicin→Paclitaxel→Cyclophosphamide
Epirubicin 150 mg/m2
Q2w x 3 cycles
Paclitaxel (Taxol) 225 mg/m2
Q2w x 3 cycles
Cyclophosphamide (Cytoxan) 2500 mg/m2
Q2w x 3 cycles
Filgrastim (Neupogen) 5 mcg/kg sc d 3-10

Moebus et al. Dose-dense sequential chemotherapy with epirubicin (E), paclitaxel (T) and cyclophosphamide (C) (ETC) in comparision to conventional dosed chemotherapy in high-risk breast cancer patients (= or > 4+LN). Mature results of an AGO-trial. 2006 San Antonio Breast Cancer Symposium. Abstract 43 (link to the abstract).

MFL
Methotrexate (MTX) 100 mg/m2 iv d1, 8
5-FU 600 mg/m2 iv d1, 8
Leucovorin 15 mg/m2 po q6h x 6 doses beginning 24 hrs after methotrexate
Q4w x 6 cycles

Fisher B et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst 1997; 89:1673 (link to the article).

Targeted therapy (back to top)

AC→TH
Doxorubicin (Adriamycin) 60 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 600 mg/m2 iv d1
Q3w x 4 cycles
Followed by
Paclitaxel (Taxol) 175 mg/m2 iv q3w x 4 cycles, or 80 mg/m2 iv qw x 12 weeks
Trastuzumab (Herceptin) 4 mg/kg loading dose beginning with paclitaxel, then 2 mg/kg iv qw x 1 year

Approved by FDA on 11/16/06 (link to FDA file).

Romond EH et al. Trastuzumab plus adjuvant chemotherapy for operable Her2-positive breast cancer. N Eng J Med 2005; 353:1673 (link to the article).

Dose-dense AC→TH
Doxorubicin (Adriamycin) 60 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 600 mg/m2 iv d1
Q2w x 4 cycles
Followed by
Paclitaxel (Taxol) 175 mg/m2 iv q2w x 4 cycles, and
Trastuzumab (Herceptin) 4 mg/kg loading dose beginning with the first cycle of paclitaxel, then 2 mg/kg iv qw during paclitaxel treatment, followed by 6 mg/kg iv q3w, for a total of 1 year
Pegfilgrastim (Neulasta) 6 mg sc d2

Dang C et al. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in Her2/neu overexpressed/amplified breast cancer. J Clin Oncol 2008; 26:1216 (link to the article).

TCH
Docetaxel (Taxotere) 75 mg/m2 iv d1 q3w x 6 cycles
Carboplatin (Paraplatin) AUC 6 iv d1 q3w x 6 cycles
Trastuzumab (Herceptin) 4 mg/kg loading dose followed by 2 mg/kg iv qw during chemotherapy; then 6 mg/kg iv q3w，for a total of 1 year

Slamon D et al. BCIRG 006: 2nd interim analysis phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients. 2006 San Antonio Breast Cancer Symposium; Abstract 52 (link to the abstract).

Chemo→H
Trastuzumab (Herceptin) can be given after completion of chemotherapy as well, loading dose 8 mg/kg，followed by 6 mg/kg，iv q3w for a total of 1 year.

Smith I et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomized controlled trial. Lancet 2007; 369:29 (link to the article).

Piccart-Gebhart MJ et al. Trastuzumab after adjuvant chemotherapy in Her2-positive breast cancer. N Eng J Med 2005; 353:1659 (link to the article).

DH→FEC
Docetaxel (Taxotere) 100 mg/m2 iv over 1 h d1 q3w x 3 cycles
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min d1 and then 2 mg/kg iv over 30 min qw x 8 (total of 9 treatments)
Followed by
5-FU 600 mg/m2 iv d1
Epirubicin 60 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 600 mg/m2 iv d1
Q3w x 3 cycles

Joensuu H et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Eng J Med 2006; 354:809 (link to the article).

Metastatic breast cancer (back to top)

Hormonal therapy

Tamoxifen
Tamoxifen 20 mg po qd

Ingle, JN et al. Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N Engl J Med 1981; 304:16 (link to the article).

Anastrozole
Anastrozole (Arimidex) 1 mg po qd

Osborne, CK et al. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a north american trial. J Clin Oncol 2002; 20:3386 (link to the article).

Anastrozole + Goserelin
Goserelin (Zoladex) 3.6 mg sc d1 qm
Anastrozole (Arimidex) 1 mg po qd, beginning on d22

Carlon RW et al. Goserelin plus anatrozole in the treatment of premenopausal hormone receptor positive, recurrent or metastatic breast cancer. 2007 ASCO annual meeting. Abstract 1030 (link to the abstract).

Letrozole
Letrozole (Femara) 2.5 mg po qd

Mouridsen, H et al. Phase III Study of Letrozole Versus Tamoxifen as First-Line Therapy of Advanced Breast Cancer in Postmenopausal Women: Analysis of Survival and Update of Efficacy From the International Letrozole Breast Cancer Group. J Clin Oncol 2003; 21:2101 (link to the article).

Exemestane
Exemestane (Aromasin) 25 mg po qd

Chia S et al. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol 2008; 26:1664 (link to the article).

Kaufmann, M et al. 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. The Exemestane Study Group. J Clin Oncol 2000; 18:1399 (link to the article).

Fulvestrant
Fulvestrant (Faslodex) 250 mg im qm or 500 mg loading dose im d1 followed by 250 mg im d14, 28 and qm thereafter

Perey L et al. Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II swiss Group for Clinical Cancer Research Trial (SAKK 21/00). Ann Oncol 2007; 18:64 (link to the article).

Howell, A et al. Fulvestrant, Formerly ICI 182,780, Is as Effective as Anastrozole in Postmenopausal Women With Advanced Breast Cancer Progressing After Prior Endocrine Treatment. J Clin Oncol 2002; 20:3396 (link to the article).

Chemotherapy (back to top)

Docetaxel
Docetaxel (Taxotere)
Regimen 1 (q3w) (preferred)
60-100 mg/m2 iv q3w

Harvey V et al. Phase III trial of comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol 2006; 24:4963 (link to the article).

Alexandre, J et al. Factors predicting for efficacy and safety of docetaxel in a compassionate-use cohort of 825 heavily pretreated advanced breast cancer patients. J Clin Oncol 2000; 18:562 (link to the article).

Regimen 2 (qw)
35-40 mg/m2 iv qw x 6 wks every 8 wks

Burstein, HJ et al. Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol 2000; 18:1212 (link to the article).

Paclitaxel
Paclitaxel (Taxol)
Regimen 1 (q3w)
175 mg/m2 iv over 3 hours q3w until progression or limiting toxicity

Bishop, JF et al. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol 1999; 17:2355 (link to the article).

Regimen 2 (qw) (preferred)
80-90 mg/m2 iv over 1 hour qw until progression or limiting toxicity

Seidman AD et al. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all Her-2 overexpressors and random assignment to trastuzumab or not in Her-2 nonoverexpressors: Final results of Cancer and Leukemia Group B Protocol 9840. J Clin Oncol 2008; 26:1642 (link to the article).

Verrill MW et al. Anglo-Celtic IV: first results of a UK National Cancer Research Network randomized phase 3 pharmacogenetic trial of weekly versus 3 weekly paclitaxel in patients with locally advanced or metastatic breast cancer (ABC). 2007 ASCO annual meeting. Abstract LBA1005 (link to the abstract).

Perez, EA et al. Multicenter Phase II Trial of Weekly Paclitaxel in Women With Metastatic Breast Cancer. J Clin Oncol 2001; 19:4216 (link to the article).

Abraxane
Abraxane
Regimen 1 (qw)
100 mg/m2 or 150 mg/m2 iv qw x 3 weeks every 4 weeks

Gradishar WJ et al. A randomized phase 2 trial of qw or q3w ABI-007 (ABX) vs. q3w solvent-based docetaxel (TXT) as first-line therapy for metastatic breast cancer (MBC). 2006 San Antonio Breast Cancer Symposium; Abstract 46 (link to the abstract).

Regimen 2 (q3w)
260 mg/m2 iv q3w

Gradishar WJ et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 2005; 23:7794 (link to the article).

Gemcitabine
Gemcitabine (Gemzar) 725 mg/m2 iv qw x 3 wks evey 4wks

Carmichael, J et al. Advanced breast cancer: a phase II trial with gemcitabine. J Clin Oncol 1995; 13:2731 (link to the article).

Vinorelbine
Vinorelbine (Navelbine) 20 mg/m2 iv over 1 hour qw, increase to 25 mg/m2 qw if the first 4 courses are well tolerated

Gasparini, G et al. Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: a phase II study. J Clin Oncol 1994; 12:2094 (link to the article).

Capecitabine
Capecitabine (Xeloda) 1250 mg/m2 po bid x 14 days q3w

Fumoleau, P et al. Multicentre, phase II study evaluating capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer. Eur J Cancer 2004; 40:536 (link to the article).

AC
Doxorubicin (Adriamycin) 60 mg/m2 iv
Cyclophosphamide (Cytoxan) 600 mg/m2 iv
Q3w

EC
Epirubicin 75 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 600 mg/m2 iv d1
Q3w

Langley RE et al. Phase III trial of epirubicin plus paclitaxel compared with epirubicin plus cyclophosphamide as first-line chemotherapy for metastatic breast cancer: United Kingdom National Cancer Research Institute Trial AB01. J Clin Oncol 2005; 23:8322 (link to the article).

AP
Doxorubicin (Adriamycin) 50 mg/m2 iv d1
Paclitaxel (Taxol) 200 mg/m2 iv over 3 hours d2
Q3w x 6-8 cycles

Gennari A et al. Lack of benefit of maintenance paclitaxel in first-line chemotherapy in metastatic breast cancer. J Clin Oncol 2006; 24:3912 (link to the article).

EP
Epirubicin 75 mg/m2 iv d1
Paclitaxel (Taxol) 200 mg/m2 iv over 3 hours d1
Q3w

Docetaxel + Capecitabine
Docetaxel (Taxotere) 75 mg/m2 iv d1
Capecitabine (Xeloda) 1000 mg/m2 po bid x 14 days
Q3w

O'Shaughnessy, J et al. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 2002; 20:2812 (link to the article).

Paclitaxel + Gemcitabine
Paclitaxel (Taxol) 175 mg/m2 iv d1
Gemcitabine (Gemzar) 1000 mg/m2 iv d1 and 8
Q3w

Albain, KS et al. Global phase III study of gemcitabine plus paclitaxel versus paclitaxel as frontline therapy for metastatic breast cancer: first report of overall survival (abstract). 2004 ASCO annual meeting; Abstract 510. (link to the abstract).

Ixabepilone (Ixempra)
Ixabepilone (Ixempra)
Premedication
Diphenhydramine (Benadrol) 50 mg po 1 hour before ixabepilone
Ranitidine (Zantac) 150 mg po 1 hour before ixabepilone
If allergic reaction, add dexamethasone 20 mg po 1 hour before ixabepilone or 20 mg iv 30 min before ixabepilone

Regimen 1
40 mg/m2 iv over 3 hours q3w

Approved by FDA on 10/16/07 (link to FDA file)

Perez EA et al. Efficacy and safety of ixabepione (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol 2007; 25:3407 (link to the article).

Thomas E et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patient with taxane-resistant metastatic breast cancer. J Clin Oncol 2007; 25:3399 (link to the article).

Roche H et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, as first-line therapy in patients with metastatic breast cancer previously treated with anthracycline chemotherapy. J Clin Oncol 2007; 25:3415 (link to the article).

Regimen 2
6 mg/m2/d iv d1-5 q3w

Denduluri N et al. Phase II trial of ixabepilone, an epothilone B analog, in patients with metastatic breast cancer previously untreated with taxanes. J Clin Oncol 2007; 25:3421 (link to the article).

Low JA et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in metastatic and locally advanced breast cancer. J Clin Oncol 2005; 23:2726 (link to the article).

Ixabepilone + Capecitabine
Ixabepilone (Ixempra) 40 mg/m2 iv over 3 hours d1
Capecitabine (Xeloda) 1000 mg/m2 po bid d1-14
Q3w until progression

Approved by FDA on 10/16/07 (link to FDA file)

Thomas ES et al. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthrocycline and taxane treatment. J Clin Oncol 2007; 25:5210 (link to the article).

Targeted therapy (back to top)

Paclitaxel + Bevacizumab
Paclitaxel (Taxol) 90 mg/m2 iv d1, 8 and 15
Bevacizumab (Avastin) 10 mg/kg iv d1 and 15
Q4w

Approved by FDA on 2/22/08.

Miller KD et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Eng J Med 2007; 357:2666 (link to the article).

Docetaxel + Bevacizumab
Docetaxel (Taxotere) 100 mg/m2 iv q3w x 9 cycles
Bevacizumab (Avastin) 7.5 mg/kg or 15 mg/kg iv q3w until progression or unacceptable toxicity

Miles D et al. Randomized, double-blind, placebo-controlled, phase III study of bevacizumab (BV) with docetaxel (D) or docetaxel with placebo (PL) as first-line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. 2008 ASCO annual meeting. LBA1011 (link to the abstract).

Capecitabine + Bevacizumab
Capecitabine (Xeloda) 1000-1250 mg/m2 po bid d1-14
Bevacizumab (Avastin) 15 mg/kg iv d1
Q3w until disease progression

Sledge G et al. Safety and efficacy of capecitabine (C) plus bevacizumab (B) as first-line metastatic breast cancer. 2007 ASCO annual meeting. Abstract 1013 (link to the abstract).

Miller K et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005; 23:792 (link to the article).

Trastuzumab
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min first wk followed by 2 mg/kg iv over 30 min qw

Cobleigh, MA et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999; 17:2639 (link to the article).

Trastuzumab + Anastrozole (for postmenopausal women with Her2 and ER/PR + cancer)
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min first wk followed by 2 mg/kg iv over 30 min qw
Anastrozole (Arimidex) 1 mg po qd

Mackey JR et al. Trastuzumab prolongs progression-free survival in hormonal-dependent and HER2-positive metastatic breast cancer. 2006 San Antonio Breast Cancer Symposium; Abstract 2 (link to the abstract).

Kaufman B et al. Trastuzumab plus anastrozole prolongs progression-free survival in postmenopausal women with HER2-positive, hormone-dependent metastatic breast cancer (MBC). 31st Congress of the European Society for Medical Oncology (ESMO) 2006; Late breaking abstract 2 (link to the abstract).

Trastuzumab + Paclitaxel q3w
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min first wk followed by 2 mg/kg iv over 30 min qw
Paclitaxel (Taxol) 175 mg/m2 iv q3w

Robert N et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 2006; 24:2786 (link to the article).

Slamon, DJ et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344:783 (link to the article).

Trastuzumab + Paclitaxel qw
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min first wk followed by 2 mg/kg iv over 30 min qw
Paclitaxel (Taxol) 90 mg/m2 iv qw

Seidman, AD et al. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol 2001; 19:2587 (link to the article).

TPC
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min d1 first wk followed by 2 mg/kg iv over 30 min d1 qw
Paclitaxel (Taxol) 175 mg/m2 iv d2 q3w
Carboplatin (Paraplatin) AUC 6 iv d2 q3w

Trastuzumab + Docetaxel (TH) q3w
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min first wk followed by 2 mg/kg iv over 30 min qw (may change to 6 mg/kg q3w after chemotherapy) until disease progression
Docetaxel (Taxotere) 100 mg/m2 iv q3w x 6-8 cycles

Pegram M et al. BCIRG 007: first overall survival analysis of randomized phase III trial of trastuzumab plus docetaxel with or without carboplatin as first line therapy in HER2 amplified metastatic breast cancer (MBC). 2007 ASCO annual meeting. Abstract LBA1008 (link to the abstract).

Marty M et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment : the M77001 study group. J Clin Oncol 2005; 23:4265 (link to the article).

Trastuzumab + Docetaxel qw
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min first wk followed by 2 mg/kg iv over 30 min qw
Docetaxel (Taxotere) 35 mg/m2 iv qw

Tedesco, KL et al. Docetaxel combined with trastuzumab is an active regimen in HER-2 3+ overexpressing and fluorescent in situ hybridization-positive metastatic breast cancer: a multi-institutional phase II trial. J Clin Oncol 2004; 22:1071 (link to the article).

Trastuzumab → Docetaxel
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min first wk followed by 2 mg/kg iv over 30 min qw
Start docetaxel upon disease progression on trastuzumab
Docetaxel (Taxotere) 100 mg/m2 iv q3w

Bontenbal M et al. Randomized study comparing efficacy/toxicity of monotherapy trastuzumab followed by monotherapy docetaxel at progression, and combination trastuzumab/docetaxel as first-line chemotherapy in HER2/neu positive, metastatic breast cancer (MBC) (HERTAX study). 2008 ASCO annual meeting. Abstract 1014 (link to the abstract).

TCH
Docetaxel (Taxotere) 75 mg/m2 iv over 1 h d1 q3w x 6-8 cycles
Carboplatin (Paraplatin) AUC 6 iv over 1 h d1 q3w x 6-8 cycles
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min first week followed by 2 mg/kg iv over 30 min qw (may change to 6 mg/kg q3w after chemotherapy) until disease progression

Pegram M et al. Results of two open-label, multicenter phase II studies of docetaxel, platinum salts, and trastuzumab in HER2-positive advanced breast cancer. J Natl Cancer Inst 2004. 96:759 (link to the article).

Trastuzumab + Capecitabine
Regimen 1
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min first week followed by 2 mg/kg iv over 30 min qw
Capecitabine (Xeloda) 1250 mg/m2 po bid d1-14 q3w

Schaller G et al. Phase II study of Capecitabine plus trastuzumab in human epidermal growth factor receptor 2-overexpressing metastatic breast cancer pretreated with anthracyclines or taxanes. J Clin Oncol 2007; 25:3246 (link to the article).

Regimen 2
Trastuzumab (Herceptin) 8 mg/kg iv loading dose followed by 6 mg/kg iv q3w
Capecitabine (Xeloda) 1250 mg/m2 po bid d1-14 q3w

Von Minchwitz G et al. Capecitabine versus capecitabine + trastuzumab in patients with HER2-positive metastatic breast cancer progressing during trastuzumab treatment: the TBP phase III study (GBG 26/BIG 3-05). 2008 ASCO annual meeting. Abstract 1025 (link to the abstract).

Bartsch R et al. Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. J Clin Oncol 2007; 25:3853 (link to the article).

Trastuzumab + Docetaxel + Capecitabine
Trastuzumab (Herceptin) 8 mg/kg iv loading followed by 6 mg/kg iv d1 q3w
Docetaxel (Taxotere) 75 mg/m2 iv d1 q3w
Capecitabine (Xeloda) 940 mg/m2 po bid d1-14 q3w

Wardley A et al. Trastuzumab plus docetaxel with or without capecitabine in patients with HER2-positive advanced/metastatic breast cancer: primary efficacy results from a randomized phase II study (CHAT). 31st Congress of the European Society for Medical Oncology (ESMO) 2006; Late breaking abstract 6 (link to the abstract).

Lapatinib + Trastuzumab
Lapatinib (Tykerb) 1000 mg po qd
Trastuzumab (Herceptin) 4 mg/kg iv over 90 min first week followed by 2 mg/kg iv over 30 min qw

O'Shaughnessy J et al. A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+ metastatic breast cancer progression on trastuzumab therapy. 2008 ASCO annual meeting. Abstract 1015 (link to the abstract).

Lapatinib + Capecitabine
Lapatinib (Tykerb) 1250 mg po qd
Capecitabine (Xeloda) 1000 mg/m2 po bid d1-14 q3w

Approved by FDA on 3/13/07 (link to FDA file)

Geyer CE et al. Lapatinib plus capecitabine for Her2-positive advanced breast cancer. N Eng J Med 2006; 355:2733 (link to the article).

Lapatinib + Paclitaxel
Lapatinib (Tykerb) 1500 mg po qd
Paclitaxel (Taxol) 175 mg/m2 iv q3w

Di Leo A et al. Lapatinib (L) with paclitaxel compared with paclitaxel as first-line treatment for patients with metastatic breast cancer: a phase III randomized, double-blinded study of 580 patients. 2007 ASCO annual meeting. Abstract 1011 (link to the abstract).

Lapatinib (for inflammatory breast cancer)
Lapatinib (Tykerb) 1500 mg po qd

Johnston S et al. Phase II study of predictive biomarker profiles for response targeting human epidermal growth factor receptor 2 (HER-2) in advanced inflammatory breast cancer with lapatinib monotherapy. J Clin Oncol 2008; 26:1066 (link to the article).

Lapatinib (for brain metastases)
Lapatinib (Tykerb) 750 mg po bid

Lin NU et al. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor 2-positive breast cancer. J Clin Oncol 2008; 26:1993 (link to the article).

Lapatinib + Capecitabine (for brain metastases)
Lapatinib (Tykerb) 1250 mg po qd
Capecitabine (Xeloda) 1000 mg/m2 po bid x 14 days q3w

Lin NU et al. Lapatinib and capecitabine for the treatment of brain metastases in patients with HER2+ breast cancer-an updated analysis from EGF-105084. 2007 San Antonio Breast Cancer Symposium. Abstract 6076 (link to the abstract).