Difference between revisions of "Breast cancer"
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!style="width: 25%"|Comparator | !style="width: 25%"|Comparator | ||
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639498/ Brambilla et al. 1976] | ||
+ | | style="background-color:#1a9851" |Phase III (C) | ||
+ | |AV | ||
+ | | style="background-color:#ffffbf" |Seems not superior | ||
|- | |- | ||
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J/abstract Bull et al. 1978] | |[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J/abstract Bull et al. 1978] | ||
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===References=== | ===References=== | ||
+ | # Brambilla C, De Lena M, Rossi A, Valagussa P, Bonadonna G. Response and survival in advanced breast cancer after two non-cross-resistant combinations. Br Med J. 1976 Apr 3;1(6013):801-4. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639498/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/1260337 PubMed] | ||
# Bull JM, Tormey DC, Li SH, Carbone PP, Falkson G, Blom J, Perlin E, Simon R. A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer. 1978 May;41(5):1649-57. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/348293 PubMed] | # Bull JM, Tormey DC, Li SH, Carbone PP, Falkson G, Blom J, Perlin E, Simon R. A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer. 1978 May;41(5):1649-57. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1649::AID-CNCR2820410501%3E3.0.CO;2-J/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/348293 PubMed] | ||
# '''EORTC 10808:''' Engelsman E, Klijn JC, Rubens RD, Wildiers J, Beex LV, Nooij MA, Rotmensz N, Sylvester R. "Classical" CMF versus a 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer: an EORTC Breast Cancer Co-operative Group Phase III Trial (10808). Eur J Cancer. 1991;27(8):966-70. [https://www.ejcancer.com/article/0277-5379(91)90259-G/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1832904 PubMed] | # '''EORTC 10808:''' Engelsman E, Klijn JC, Rubens RD, Wildiers J, Beex LV, Nooij MA, Rotmensz N, Sylvester R. "Classical" CMF versus a 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer: an EORTC Breast Cancer Co-operative Group Phase III Trial (10808). Eur J Cancer. 1991;27(8):966-70. [https://www.ejcancer.com/article/0277-5379(91)90259-G/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1832904 PubMed] |
Revision as of 22:53, 3 January 2019
Section editor transclusions Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page. If you still can't find it, please let us know so we can add it!
- Note: this page contains regimens which are not biomarker-specific, although they may have been studied in patients selected by biomarker. The following links will take you to biomarker-specific subpages:
- Regimens for ER/PR positive breast cancer are here.
- Regimens for HER2 positive breast cancer are here.
- Regimens for Triple negative breast cancer (TNBC) are here.
- Regimens for BRCA-mutated breast cancer are here.
- Regimens for CNS metastases are here.
- Because docetaxel and paclitaxel are both often abbreviated as "T," we try to always make clear in the regimen name which agent is being used.
143 regimens on this page
330 variants on this page
|
Guidelines
ASCO
- 2018: Denduluri et al. Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO clinical practice guideline focused update PubMed
- 2016: Burstein et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline update on ovarian suppression PubMed
- 2016: Harris et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline
- 2015: van Poznak et al. Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology Clinical practice guideline
Older
- 2014: Partridge et al. Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2-negative (or unknown) advanced breast cancer: American Society of Clinical Oncology Clinical Practice Guideline
ASCO/CCO
- 2017: Role of bone-modifying agents in metastatic breast cancer: an American Society of Clinical Oncology–Cancer Care Ontario focused guideline update PubMed
ESMO
- 2015: Senkus et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
ESO/ESMO
- 2018: Cardoso et al. 4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)
Older
- 2017: Cardoso et al. 3rd ESO-ESMO International consensus guidelines for advanced breast cancer (ABC3) PubMed
- 2014: Cardoso et al. ESO-ESMO 2nd International consensus guidelines for advanced breast cancer (ABC2)
- 2012: Cardoso et al. 1st International consensus guidelines for advanced breast cancer (ABC 1)
NCCN
St Gallen Breast Guidelines
- 2017: Curigliano et al. St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2017
Older
- 2015: Coates et al. Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015
Neoadjuvant chemotherapy
AC
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AC: Adriamycin (Doxorubicin) & Cyclophosphamide
Variant #1, 4 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fisher et al. 1997 (NSABP B-18) | Phase III (E) | Adjuvant AC | Superior resectability |
Bear et al. 2003 (NSABP B-27) | Phase III (C) | See link | See link |
von Minckwitz et al. 2005 (GeparDuo) | Phase III (E) | See link | See link |
Lee et al. 2007 | Phase III (C) | TX | Seems to have inferior pCR rate |
Bear et al. 2012 (NSABP B-40) | Phase III (C) | See link | See link |
Robidoux et al. 2013 (NSABP B-41) | Non-randomized portion of RCT | ||
Park et al. 2016 (I-SPY 2) | Non-randomized portion of RCT |
Note: patients in NSABP B-41 and I-SPY 2 were HER2-positive.
Preceding treatment
- NSABP B-40: T (Taxotere) x 4 versus TX x 4 versus TG x 4
- I-SPY 2: Neratinib & Paclitaxel x 12 wk versus TH x 12 wk
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- NSABP B-18 & B-40: Surgery
- Lee et al. 2007: Surgery, then TX x 4
- NSABP B-27: T (Taxotere) x 4, then surgery versus surgery versus surgery, then T (Taxotere) x 4
- GeparDuo: T (Taxotere) x 4, then surgery
- NSABP B-41: TH versus THL versus TL, then surgery
- I-SPY 2: Surgery
Variant #2, 5 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ellis et al. 2011 (SWOG 0012) | Phase III (C) | Weekly doxorubicin & daily paclitaxel | 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.
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 5 cycles
Subsequent treatment
- Weekly Paclitaxel x 12, then surgery
Variant #3, 6 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Smith et al. 2004 (TOPIC) | Phase III (C) | ECisF | Seems not superior |
Evans et al. 2005 | Phase III (C) | AD | Seems not superior |
Chua et al. 2005 (TOPIC 2) | Phase III (C) | VE | Seems not superior |
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
References
- NSABP B-18: Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB Jr, Fisher ER, Wickerham DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NV. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997 Jul;15(7):2483-93. link to original article contains verified protocol PubMed
- Update: Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. link to original article PubMed
- Update: Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst. 2001;(30):96-102. PubMed
- 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
- Pooled update: Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. link to original article PubMed
- NSABP B-27: Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N; National Surgical Adjuvant Breast and Bowel Project Protocol B-27. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003 Nov 15;21(22):4165-74. Epub 2003 Oct 14. link to original article contains verified protocol PubMed
- Update: Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006 May 1;24(13):2019-27. Epub 2006 Apr 10. link to original article PubMed
- Pooled update: Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. link to original article PubMed
- TOPIC: Smith IE, A'Hern RP, Coombes GA, Howell A, Ebbs SR, Hickish TF, O'Brien ME, Mansi JL, Wilson CB, Robinson AC, Murray PA, Price CG, Perren TJ, Laing RW, Bliss JM; TOPIC Trial Group. A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neo-adjuvant treatment of early breast cancer: 5 year results of the TOPIC trial. Ann Oncol. 2004 May;15(5):751-8. link to original article contains protocol PubMed
- GeparDuo: von Minckwitz G, Raab G, Caputo A, Schütte M, Hilfrich J, Blohmer JU, Gerber B, Costa SD, Merkle E, Eidtmann H, Lampe D, Jackisch C, du Bois A, Kaufmann M. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol. 2005 Apr 20;23(12):2676-85. link to original article contains verified protocol PubMed
- Evans TR, Yellowlees A, Foster E, Earl H, Cameron DA, Hutcheon AW, Coleman RE, Perren T, Gallagher CJ, Quigley M, Crown J, Jones AL, Highley M, Leonard RC, Mansi JL. Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an Anglo-Celtic Cooperative Oncology Group study. J Clin Oncol. 2005 May 1;23(13):2988-95. link to original article PubMed
- Update: Mansi JL, Yellowlees A, Lipscombe J, Earl HM, Cameron DA, Coleman RE, Perren T, Gallagher CJ, Quigley M, Crown J, Jones AL, Highley M, Leonard RC, Evans TR. Five-year outcome for women randomised in a phase III trial comparing doxorubicin and cyclophosphamide with doxorubicin and docetaxel as primary medical therapy in early breast cancer: an Anglo-Celtic Cooperative Oncology Group study. Breast Cancer Res Treat. 2010 Aug;122(3):787-94. Epub 2010 Jun 18. link to original article PubMed
- TOPIC 2: Chua S, Smith IE, A'Hern RP, Coombes GA, Hickish TF, Robinson AC, Laing RW, O'Brien ME, Ebbs SR, Hong A, Wardley A, Mughal T, Verrill M, Dubois D, Bliss JM; TOPIC Trial Group. Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response and tolerability in a randomised phase III trial (TOPIC 2). Ann Oncol. 2005 Sep;16(9):1435-41. Epub 2005 Jun 9. link to original article contains protocol PubMed
- Lee KS, Ro J, Nam BH, Lee ES, Kwon Y, Kwon HS, Chung KW, Kang HS, Kim EA, Kim SW, Shin KH, Kim SK. A randomized phase-III trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage II/III breast cancer. Breast Cancer Res Treat. 2008 Jun;109(3):481-9. Epub 2007 Jul 26. link to original article contains protocol PubMed
- SWOG 0012: Ellis GK, Barlow WE, Gralow JR, Hortobagyi GN, Russell CA, Royce ME, Perez EA, Lew D, Livingston RB. Phase III comparison of standard doxorubicin and cyclophosphamide versus weekly doxorubicin and daily oral cyclophosphamide plus granulocyte colony-stimulating factor as neoadjuvant therapy for inflammatory and locally advanced breast cancer: SWOG 0012. J Clin Oncol. 2011 Mar 10;29(8):1014-21. Epub 2011 Jan 10. link to original article contains verified protocol link to PMC article PubMed
- NSABP B-40: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. link to original article link to PMC article PubMed
- Update: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. link to original article link to PMC article PubMed
- NSABP B-41: Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. link to original article contains protocol PubMed
- I-SPY 2: Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article contains verified protocol link to PMC article PubMed
- ETNA: Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA, Magazzù D, De Fato R, Valagussa P, Tusquets I. Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/HER2-negative breast cancer-the Evaluating Treatment with Neoadjuvant Abraxane (ETNA) trial: a randomized phase 3 clinical trial. JAMA Oncol. 2018 Mar 1;4(3):302-308. Epub 2018 Jan 11. link to original article PubMed
AC & Bevacizumab
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AC+Bev: Adriamycin (Doxorubicin), Cyclophosphamide, Bevacizumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bear et al. 2012 (NSABP B-40) | Phase III (E) | See link | See link |
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
- T+Bev x 4 versus TX+Bev x 4 versus TG+Bev x 4
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Bevacizumab (Avastin) as follows:
- Cycles 1 & 2: 15 mg/kg IV once on day 1
- Cycles 3 & 4: none
21-day cycle for 4 cycles
Subsequent treatment
- Surgery, then adjuvant bevacizumab
References
- Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. link to original article link to PMC article PubMed
- Update: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. link to original article link to PMC article PubMed
ddAC
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ddAC: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide
Regimen
Study | Evidence |
---|---|
Burstein et al. 2005 | Non-randomized |
Park et al. 2016 (I-SPY 2) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in I-SPY 2 were HER2-positive.
Preceding treatment
- I-SPY 2: Neratinib & Paclitaxel x 12 wk versus TH x 12 wk
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2, given 24 hours after chemotherapy
- Burstein et al. 2005: Darbepoetin alfa (Aranesp) 200 mcg SC once on day 1 for patients with Hb 10 to 12 g/dL; see paper for additional dose adjustments
14-day cycle for 4 cycles
Subsequent treatment
- Burstein et al. 2005: Optional dose-dense paclitaxel, then surgery or surgery, then dose-dense paclitaxel; this was not a randomization
- I-SPY 2: Surgery
References
- Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. link to original article contains verified protocol PubMed
- Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article contains verified protocol link to PMC article PubMed
DE
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DE: Docetaxel & Epirubicin
ED: Epirubicin & Docetaxel
ET: Epirubicin & Taxotere (Docetaxel)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Han et al. 2009 | Phase III (E) | ED x 4 | Seems to have superior pCR rate |
Steger et al. 2013 (ABCSG-24) | Phase III (C) | EDC | Seems to have inferior pCR rate |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
References
- Han S, Kim J, Lee J, Chang E, Gwak G, Cho H, Yang KH, Park S, Park K. Comparison of 6 cycles versus 4 cycles of neoadjuvant epirubicin plus docetaxel chemotherapy in stages II and III breast cancer. Eur J Surg Oncol. 2009 Jun;35(6):583-7. Epub 2009 Feb 5. link to original article contains protocol PubMed
- ABCSG-24: Steger GG, Greil R, Lang A, Rudas M, Fitzal F, Mlineritsch B, Hartmann BL, Bartsch R, Melbinger E, Hubalek M, Stoeger H, Dubsky P, Ressler S, Petzer AL, Singer CF, Muss C, Jakesz R, Gampenrieder SP, Zielinski CC, Fesl C, Gnant M; Austrian Breast and Colorectal Study Group (ABCSG). Epirubicin and docetaxel with or without capecitabine as neoadjuvant treatment for early breast cancer: final results of a randomized phase III study (ABCSG-24). Ann Oncol. 2014 Feb;25(2):366-71. Epub 2013 Dec 16. link to original article contains protocol PubMed
Docetaxel monotherapy
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D: Docetaxel
T: Taxotere (Docetaxel)
Variant #1, 75 mg/m2 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bear et al. 2012 (NSABP B-40) | Phase III (C) | See link | See link |
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.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Variant #2, 100 mg/m2 x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Earl et al. 2015 (ARTemis) | Phase III (C) | Docetaxel & Bevacizumab | Seems to have inferior pCR rate |
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.
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Variant #3, 100 mg/m2 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bear et al. 2003 (NSABP B-27) | Phase III (E) | See link | See link |
von Minckwitz et al. 2005 (GeparDuo) | Phase III (E) | See link | See link |
von Minckwitz et al. 2012 (GeparQuinto) | Phase III (C) | See link | See link |
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
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
References
- NSABP B-27: Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N; National Surgical Adjuvant Breast and Bowel Project Protocol B-27. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003 Nov 15;21(22):4165-74. Epub 2003 Oct 14. link to original article contains verified protocol PubMed
- Update: Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006 May 1;24(13):2019-27. Epub 2006 Apr 10. link to original article PubMed
- Pooled update: Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. link to original article PubMed
- GeparDuo: von Minckwitz G, Raab G, Caputo A, Schütte M, Hilfrich J, Blohmer JU, Gerber B, Costa SD, Merkle E, Eidtmann H, Lampe D, Jackisch C, du Bois A, Kaufmann M. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol. 2005 Apr 20;23(12):2676-85. link to original article contains verified protocol PubMed
- GeparQuinto: von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. link to original article contains verified protocol PubMed
- NSABP B-40: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. link to original article link to PMC article PubMed
- Update: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. link to original article link to PMC article PubMed
- ARTemis: Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Abraham J, Thomas J, Provenzano E, Hughes-Davies L, Gounaris I, McAdam K, Chan S, Ahmad R, Hickish T, Houston S, Rea D, Bartlett J, Caldas C, Cameron DA, Hayward L; ARTemis Investigators. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):656-66. Epub 2015 May 11. link to original article contains verified protocol PubMed
Docetaxel & Bevacizumab
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Bev+D: Bevacizumab & Docetaxel
T+Bev: Taxotere (Docetaxel) & Bevacizumab
Variant #1, docetaxel 75 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bear et al. 2012 (NSABP B-40) | Phase III (E) | See link | See link |
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.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Variant #2, docetaxel 100 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Earl et al. 2015 (ARTemis) | Phase III (E) | Docetaxel | Seems to have superior pCR rate |
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. A total of four bevacizumab doses are given, with the fourth given with the first cycle of FEC.
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
References
- NSABP B-40: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. link to original article link to PMC article PubMed
- Update: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. link to original article link to PMC article PubMed
- ARTemis: Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Abraham J, Thomas J, Provenzano E, Hughes-Davies L, Gounaris I, McAdam K, Chan S, Ahmad R, Hickish T, Houston S, Rea D, Bartlett J, Caldas C, Cameron DA, Hayward L; ARTemis Investigators. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):656-66. Epub 2015 May 11. link to original article contains verified protocol PubMed
EC
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EC: Epirubicin & Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Untch et al. 2011 (PREPARE) | Phase III (C) | See link | See link |
von Minckwitz et al. 2010 (GeparQuattro) | Non-randomized portion of RCT | ||
von Minckwitz et al. 2012 (GeparQuinto) | Phase III (C) | See link | See link |
Earl et al. 2013 (Neo-tAnGo) | Phase III (*) | See link | See link |
Untch et al. 2016 (GeparSepto) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm in this context.
Preceding treatment
- GeparSepto: nab-Paclitaxel x 4 versus weekly Paclitaxel x 12
- Neo-tAnGo (taxanes-EC arm): ddT x 4 versus ddTG x 4
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- GeparQuattro: T (Taxotere) x 4 versus T-X versus TX, then surgery
- GeparQuinto: Docetaxel, then surgery
- Neo-tAnGo (EC-taxane arms): ddT x 4 versus ddTG x 4, then surgery
- GeparSepto: Surgery
References
- PREPARE: Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C, Lück HJ, Stickeler E, Urbaczyk H, Liedtke B, Beckmann MW, Salat C, Harbeck N, Müller V, Schmidt M, Hasmüller S, Lenhard M, Nekljudova V, Lebeau A, Loibl S, Fasching PA; Arbeitsgemeinschaft Gynäkologische Onkologie PREPARE investigators. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer--outcome on prognosis. Ann Oncol. 2011 Sep;22(9):1999-2006. Epub 2011 Mar 7. link to original article contains protocol PubMed
- GeparQuattro: von Minckwitz G, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, Bauerfeind I, Hilfrich J, Eidtmann H, Gerber B, Hanusch C, Kühn T, du Bois A, Blohmer JU, Thomssen C, Dan Costa S, Jackisch C, Kaufmann M, Mehta K, Untch M. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol. 2010 Apr 20;28(12):2015-23. Epub 2010 Mar 22. link to original article contains protocol PubMed
- GeparQuinto: von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. link to original article contains verified protocol PubMed
- Neo-tAnGo: Earl HM, Vallier AL, Hiller L, Fenwick N, Young J, Iddawela M, Abraham J, Hughes-Davies L, Gounaris I, McAdam K, Houston S, Hickish T, Skene A, Chan S, Dean S, Ritchie D, Laing R, Harries M, Gallagher C, Wishart G, Dunn J, Provenzano E, Caldas C; Neo-tAnGo Investigators. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):201-12. Epub 2013 Dec 19. link to original article contains verified protocol PubMed
- GeparSepto: Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kümmel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Darb-Esfahani S, Schmitt WD, Dan Costa S, Gerber B, Engels K, Nekljudova V, Loibl S, von Minckwitz G; German Breast Group (GBG).; Arbeitsgemeinschaft Gynäkologische Onkologie—Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. Epub 2016 Feb 8. 2016 Mar;17(3):345-56. link to original article contains verified protocol PubMed
- Update: Furlanetto J, Jackisch C, Untch M, Schneeweiss A, Schmatloch S, Aktas B, Denkert C, Wiebringhaus H, Kümmel S, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Costa SD, Gerber B, Nekljudova V, Loibl S, von Minckwitz G. Efficacy and safety of nab-paclitaxel 125 mg/m(2) and nab-paclitaxel 150 mg/m(2) compared to paclitaxel in early high-risk breast cancer: results from the neoadjuvant randomized GeparSepto study (GBG 69). Breast Cancer Res Treat. 2017 Jun;163(3):495-506. Epub 2017 Mar 17. link to original article PubMed
- ETNA: Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA, Magazzù D, De Fato R, Valagussa P, Tusquets I. Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/HER2-negative breast cancer-the Evaluating Treatment with Neoadjuvant Abraxane (ETNA) trial: a randomized phase 3 clinical trial. JAMA Oncol. 2018 Mar 1;4(3):302-308. Epub 2018 Jan 11. link to original article contains verified protocol PubMed
DI EC
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DI EC: Dose-Intense Epirubicin & Cyclophosphamide
Regimen
Study | Evidence |
---|---|
Gonçalves et al. 2015 (UNICANCER PEGASE 07) | Non-randomized portion of RCT |
This regimen required hematopoeitic stem cell support; see paper for details.
Chemotherapy
- Epirubicin (Ellence) 150 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 4000 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery, then Docetaxel & 5-FU versus no further treatment
References
- UNICANCER PEGASE 07: Gonçalves A, Pierga JY, Ferrero JM, Mouret-Reynier MA, Bachelot T, Delva R, Fabbro M, Lerebours F, Lotz JP, Linassier C, Dohollou N, Eymard JC, Leduc B, Lemonnier J, Martin AL, Boher JM, Viens P, Roché H. UNICANCER-PEGASE 07 study: a randomized phase III trial evaluating postoperative docetaxel-5FU regimen after neoadjuvant dose-intense chemotherapy for treatment of inflammatory breast cancer. Ann Oncol. 2015 Aug;26(8):1692-7. Epub 2015 May 5. link to original article contains protocol PubMed
EP
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EP: Epirubicin & Paclitaxel
ET: Epirubicin & Taxol (Paclitaxel)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Frasci et al. 2006 | Phase III (C) | PET | Seems to have inferior pCR rate |
Untch et al. 2009 | Phase III (C) | ddE, then ddP | Seems to have inferior OS |
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.
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Frasci et al. 2006: Surgery, then CMF x 4 or FEC x 4, depending on number of involved lymph nodes
- Untch et al. 2009: Surgery, then CMF x 3
References
- Frasci G, D'Aiuto G, Comella P, Thomas R, Botti G, Di Bonito M, De Rosa V, Iodice G, Rubulotta MR, Comella G; Southern Italy Cooperative Oncology Group (SICOG). Weekly cisplatin, epirubicin, and paclitaxel with granulocyte colony-stimulating factor support vs triweekly epirubicin and paclitaxel in locally advanced breast cancer: final analysis of a SICOG phase III study. Br J Cancer. 2006 Oct 23;95(8):1005-12. link to original article link to PMC article PubMed
- Untch M, Möbus V, Kuhn W, Muck BR, Thomssen C, Bauerfeind I, Harbeck N, Werner C, Lebeau A, Schneeweiss A, Kahlert S, von Koch F, Petry KU, Wallwiener D, Kreienberg R, Albert US, Lück HJ, Hinke A, Jänicke F, Konecny GE. Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol. 2009 Jun 20;27(18):2938-45. Epub 2009 Apr 13. link to original article contains verified protocol PubMed
FAC
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FAC: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide
Variant #1, 600/50/600
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baldini et al. 1997 | Phase III (C) | DES-CAF | Seems not superior |
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2/day IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Variant #2, 1000/50/500
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Buzdar et al. 1999 | Phase III (C) | q3wk Paclitaxel x 4 | Seems not superior |
Green et al. 2005 | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Green et al. 2005: Weekly paclitaxel x 12 versus q3wk paclitaxel x 4
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 4
- Doxorubicin (Adriamycin) 16.7 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 50 mg/m2)
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Variant #3, 2000/50/100
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Scholl et al. 1994 | Phase III (E) | Adjuvant FAC | Seems to have superior OS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1, 3, 5, 8
- Doxorubicin (Adriamycin) 25 mg/m2/day IV once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days 1 & 5
28-day cycle for 4 cycles
Subsequent treatment
References
- S6: Scholl SM, Fourquet A, Asselain B, Pierga JY, Vilcoq JR, Durand JC, Dorval T, Palangié T, Jouve M, Beuzeboc P, et al. Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: preliminary results of a randomised trial: S6. Eur J Cancer. 1994;30A(5):645-52. link to SD article contains verified protocol PubMed
- Baldini E, Gardin G, Giannessi P, Brema F, Camorriano A, Carnino F, Naso C, Pastorino G, Pronzato P, Rosso R, Rubagotti A, Torretta G, Conte PF; North-West Oncology Group (GONO) Study, Italy. A randomized trial of chemotherapy with or without estrogenic recruitment in locally advanced breast cancer. Tumori. 1997 Sep-Oct;83(5):829-33. link to original article contains protocol PubMed
- Buzdar AU, Singletary SE, Theriault RL, Booser DJ, Valero V, Ibrahim N, Smith TL, Asmar L, Frye D, Manuel N, Kau SW, McNeese M, Strom E, Hunt K, Ames F, Hortobagyi GN. Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer. J Clin Oncol. 1999 Nov;17(11):3412-7. link to original article contains verified protocol PubMed
- Green MC, Buzdar AU, Smith T, Ibrahim NK, Valero V, Rosales MF, Cristofanilli M, Booser DJ, Pusztai L, Rivera E, Theriault RL, Carter C, Frye D, Hunt KK, Symmans WF, Strom EA, Sahin AA, Sikov W, Hortobagyi GN. Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol. 2005 Sep 1;23(25):5983-92. Epub 2005 Aug 8. link to original article contains verified protocol PubMed
FEC
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FEC: Fluorouracil, Epirubicin, Cyclophosphamide
Variant #1, 500/75/500 ("FEC-75")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Buzdar et al. 2013 (ACOSOG Z1041) | Phase III (C) | See link | See link |
Note that patients in this trial had HER2-positive breast cancer. 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.
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- TH (Taxol) x 12 wk, then surgery
Variant #2, 500/100/500 x 3
Study | Evidence |
---|---|
Earl et al. 2015 (ARTemis) | Non-randomized portion of RCT |
Note that for the patients randomized to the bevacizumab arm, a fourth dose was given with the first cycle of FEC. 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
- Docetaxel & Bevacizumab x 3 versus Docetaxel x 3
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Variant #3, 500/100/500 x 4
Study | Evidence |
---|---|
Kelly et al. 2012 | Non-randomized portion of RCT |
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
- Weekly paclitaxel x 12 versus XT
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Variant #4, 500/100/600 x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Schneeweiss et al. 2013 (TRYPHAENA) | Randomized Phase II (C) | See link | Not reported |
Note: patients enrolled in this trial had HER2+ disease. 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.
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Variant #5, 600/60/600 x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baldini et al. 2003 | Phase III (C) | ddFEC | Seems not superior |
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- Surgery, then CEF/CMF x 3
Variant #6, 600/60/600 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
van der Hage et al. 2001 (EORTC 10902) | Phase III (E) | Adjuvant FEC | Seems not superior |
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Variant #7, 1000/75/500 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Buzdar et al. 2005 | Randomized (C) | See link | See link |
Note that patients in this trial had HER2-positive breast cancer. 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
- CI paclitaxel x 4
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 4
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Variant #8, 1000/120/1050 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Therasse et al. 2003 | Phase III (C) | ddEC | Seems not superior |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Epirubicin (Ellence) 60 mg/m2 IV once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 75 mg/m2 PO once per day on days 1 to 14
28-day cycle for 6 cycles
Subsequent treatment
References
- EORTC 10902: van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001 Nov 15;19(22):4224-37. link to original article contains verified protocol PubMed
- Update: van Nes JG, Putter H, Julien JP, Tubiana-Hulin M, van de Vijver M, Bogaerts J, de Vos M, van de Velde CJ; Cooperating Investigators of the EORTC. Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902. Breast Cancer Res Treat. 2009 May;115(1):101-13. Epub 2008 May 18. link to original article PubMed
- Baldini E, Gardin G, Giannessi PG, Evangelista G, Roncella M, Prochilo T, Collecchi P, Rosso R, Lionetto R, Bruzzi P, Mosca F, Conte PF. Accelerated versus standard cyclophosphamide, epirubicin and 5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil: a randomized phase III trial in locally advanced breast cancer. Ann Oncol. 2003 Feb;14(2):227-32. link to original article contains verified protocol PubMed
- Therasse P, Mauriac L, Welnicka-Jaskiewicz M, Bruning P, Cufer T, Bonnefoi H, Tomiak E, Pritchard KI, Hamilton A, Piccart MJ; EORTC. Final results of a randomized phase III trial comparing cyclophosphamide, epirubicin, and fluorouracil with a dose-intensified epirubicin and cyclophosphamide + filgrastim as neoadjuvant treatment in locally advanced breast cancer: an EORTC-NCIC-SAKK multicenter study. J Clin Oncol. 2003 Mar 1;21(5):843-50. link to original article contains protocol PubMed
- Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005 Jun 1;23(16):3676-85. Epub 2005 Feb 28. link to original article contains verified protocol PubMed
- Update: Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007 Jan 1;13(1):228-33. link to original article PubMed
- Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU. Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol. 2012 Mar 20;30(9):930-5. Epub 2012 Feb 13. link to original article contains verified protocol PubMed
- TRYPHAENA: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. link to original article contains verified protocol PubMed
- ACOSOG Z1041: Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig G, Royce M, McCall LM, Ewer MS, Hunt KK; American College of Surgeons Oncology Group investigators. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1317-25. Epub 2013 Nov 13. link to original article link to PMC article contains verified protocol PubMed
- ARTemis: Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Abraham J, Thomas J, Provenzano E, Hughes-Davies L, Gounaris I, McAdam K, Chan S, Ahmad R, Hickish T, Houston S, Rea D, Bartlett J, Caldas C, Cameron DA, Hayward L; ARTemis Investigators. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):656-66. Epub 2015 May 11. link to original article contains verified protocol PubMed
- ETNA: Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA, Magazzù D, De Fato R, Valagussa P, Tusquets I. Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/HER2-negative breast cancer-the Evaluating Treatment with Neoadjuvant Abraxane (ETNA) trial: a randomized phase 3 clinical trial. JAMA Oncol. 2018 Mar 1;4(3):302-308. Epub 2018 Jan 11. link to original article PubMed
Paclitaxel monotherapy, weekly
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T: Taxol (Paclitaxel)
Variant #1, 80 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Green et al. 2005 | Phase III (E) | q3wk paclitaxel | Seems to have superior pCR rate |
Ellis et al. 2011 (SWOG 0012) | Non-randomized portion of RCT | ||
Kelly et al. 2012 | Phase III (C) | XT | Seems not superior |
Untch et al. 2016 (GeparSepto) | Phase III (C) | nab-Paclitaxel | Inferior pCR rate |
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
- SWOG 0012: AC x 5 versus weekly doxorubicin & daily cyclophosphamide
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
12-week course
Subsequent treatment
- Green et al. 2005: FAC x 4, then surgery
- SWOG 0012: Surgery
- Kelly et al 2012: FEC x 4, then surgery
- GeparSepto: EC x 4, then surgery
Variant #2, 90 mg/m2, 3 out of 4 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gianni et al. 2018 (ETNA) | Phase III (C) | nab-Paclitaxel | 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.
Chemotherapy
- Paclitaxel (Taxol) 90 mg/m2 IV once per day on days 1, 8, 15
4-week cycle for 4 cycles
Subsequent treatment
References
- Green MC, Buzdar AU, Smith T, Ibrahim NK, Valero V, Rosales MF, Cristofanilli M, Booser DJ, Pusztai L, Rivera E, Theriault RL, Carter C, Frye D, Hunt KK, Symmans WF, Strom EA, Sahin AA, Sikov W, Hortobagyi GN. Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol. 2005 Sep 1;23(25):5983-92. Epub 2005 Aug 8. link to original article contains verified protocol PubMed
- SWOG 0012: Ellis GK, Barlow WE, Gralow JR, Hortobagyi GN, Russell CA, Royce ME, Perez EA, Lew D, Livingston RB. Phase III comparison of standard doxorubicin and cyclophosphamide versus weekly doxorubicin and daily oral cyclophosphamide plus granulocyte colony-stimulating factor as neoadjuvant therapy for inflammatory and locally advanced breast cancer: SWOG 0012. J Clin Oncol. 2011 Mar 10;29(8):1014-21. Epub 2011 Jan 10. link to original article contains verified protocol link to PMC article PubMed
- Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU. Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol. 2012 Mar 20;30(9):930-5. Epub 2012 Feb 13. link to original article contains verified protocol PubMed
- GeparSepto: Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kümmel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Darb-Esfahani S, Schmitt WD, Dan Costa S, Gerber B, Engels K, Nekljudova V, Loibl S, von Minckwitz G; German Breast Group (GBG).; Arbeitsgemeinschaft Gynäkologische Onkologie—Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. Epub 2016 Feb 8. 2016 Mar;17(3):345-56. link to original article contains verified protocol PubMed
- Update: Furlanetto J, Jackisch C, Untch M, Schneeweiss A, Schmatloch S, Aktas B, Denkert C, Wiebringhaus H, Kümmel S, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Costa SD, Gerber B, Nekljudova V, Loibl S, von Minckwitz G. Efficacy and safety of nab-paclitaxel 125 mg/m(2) and nab-paclitaxel 150 mg/m(2) compared to paclitaxel in early high-risk breast cancer: results from the neoadjuvant randomized GeparSepto study (GBG 69). Breast Cancer Res Treat. 2017 Jun;163(3):495-506. Epub 2017 Mar 17. link to original article PubMed
- ETNA: Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA, Magazzù D, De Fato R, Valagussa P, Tusquets I. Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/HER2-negative breast cancer-the Evaluating Treatment with Neoadjuvant Abraxane (ETNA) trial: a randomized phase 3 clinical trial. JAMA Oncol. 2018 Mar 1;4(3):302-308. Epub 2018 Jan 11. link to original article contains verified protocol PubMed
Paclitaxel monotherapy, dose-dense (q2wk)
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ddT: dose-dense Taxol (Paclitaxel)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Burstein et al. 2005 | Non-randomized | ||
Earl et al. 2013 (Neo-tAnGo) | Phase III (*) | See link | See link |
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
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Supportive medications
- Burstein et al. 2005: Pegfilgrastim (Neulasta) 6 mg SC once on day 2
- Neo-tAnGo: primary propyhylaxis not provided
14-day cycle for 4 cycles
Subsequent treatment
- Burstein et al. 2005 and Neo-tAnGo (EC-ddT arm): Surgery
- Neo-tAnGo (ddT-EC arm): EC x 4, then surgery
References
- Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. link to original article contains verified protocol PubMed
- Neo-tAnGo: Earl HM, Vallier AL, Hiller L, Fenwick N, Young J, Iddawela M, Abraham J, Hughes-Davies L, Gounaris I, McAdam K, Houston S, Hickish T, Skene A, Chan S, Dean S, Ritchie D, Laing R, Harries M, Gallagher C, Wishart G, Dunn J, Provenzano E, Caldas C; Neo-tAnGo Investigators. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):201-12. Epub 2013 Dec 19. link to original article contains verified protocol PubMed
Paclitaxel, nanoparticle albumin-bound monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Untch et al. 2016 (GeparSepto) | Phase III (E) | Weekly Paclitaxel | Superior pCR rate |
Note: this is the dose after study amendment due to increased treatment discontinuation and sensory neuropathy. 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.
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 125 mg/m2 IV once per day on days 1, 8, 15
21-day cycle for 4 cycles
Subsequent treatment
References
- GeparSepto: Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kümmel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Darb-Esfahani S, Schmitt WD, Dan Costa S, Gerber B, Engels K, Nekljudova V, Loibl S, von Minckwitz G; German Breast Group (GBG).; Arbeitsgemeinschaft Gynäkologische Onkologie—Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. Epub 2016 Feb 8. 2016 Mar;17(3):345-56. link to original article contains verified protocol PubMed
- Update: Furlanetto J, Jackisch C, Untch M, Schneeweiss A, Schmatloch S, Aktas B, Denkert C, Wiebringhaus H, Kümmel S, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Costa SD, Gerber B, Nekljudova V, Loibl S, von Minckwitz G. Efficacy and safety of nab-paclitaxel 125 mg/m(2) and nab-paclitaxel 150 mg/m(2) compared to paclitaxel in early high-risk breast cancer: results from the neoadjuvant randomized GeparSepto study (GBG 69). Breast Cancer Res Treat. 2017 Jun;163(3):495-506. Epub 2017 Mar 17. link to original article PubMed
- ETNA: Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA, Magazzù D, De Fato R, Valagussa P, Tusquets I. Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/HER2-negative breast cancer-the Evaluating Treatment with Neoadjuvant Abraxane (ETNA) trial: a randomized phase 3 clinical trial. JAMA Oncol. 2018 Mar 1;4(3):302-308. Epub 2018 Jan 11. link to original article PubMed
TAC (Taxotere)
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TAC: Taxotere (Docetaxel), Adriamycin (Doxorubicin), Cyclophosphamide
ATC: Adriamycin (Doxorubicin), Taxotere (Docetaxel), Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2008 (GeparTrio) | Phase III (E) | TAC x 2, then NX x 4 | Non-inferior sonographic response |
Vriens et al. 2013 (INTENS) | Phase III (E) | AC, then T | Seems not superior |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
References
- GeparTrio: von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C, Loibl S, Mehta K, Kaufmann M; German Breast Group. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst. 2008 Apr 16;100(8):542-51. Epub 2008 Apr 8. link to original article contains verified protocol PubMed
- INTENS: Vriens BE, Aarts MJ, de Vries B, van Gastel SM, Wals J, Smilde TJ, van Warmerdam LJ, de Boer M, van Spronsen DJ, Borm GF, Tjan-Heijnen VC; Breast Cancer Trialists' Group of the Netherlands (BOOG). Doxorubicin/cyclophosphamide with concurrent versus sequential docetaxel as neoadjuvant treatment in patients with breast cancer. Eur J Cancer. 2013 Oct;49(15):3102-10. Epub 2013 Jul 10. link to original article contains protocol PubMed
- Update: Vriens BEPJ, Vriens IJH, Aarts MJB, van Gastel SM, van den Berkmortel FWPJ, Smilde TJ, van Warmerdam LJC, van Spronsen DJ, Peer PGM, de Boer M, Tjan-Heijnen VCG; Breast Cancer Trialists’ Group of the Netherlands (BOOG). Improved survival for sequentially as opposed to concurrently delivered neoadjuvant chemotherapy in non-metastatic breast cancer. Breast Cancer Res Treat. 2017 Oct;165(3):593-600. Epub 2017 Jul 3. link to original article link to PMC article PubMed
Neoadjuvant response criteria
Clinical response rate (cRR)
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Although fairly dated, some trials such as ACOSOG Z1031 make use of the WHO criteria for response to neoadjuvant therapy. Included here primarily for historical purposes.
References
- Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207-14. link to original article PubMed
Miller-Payne scoring system
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- Grade 1: No change or some changes to individual malignant cells, but no reduction in overall cellularity
- Grade 2: Minor loss of tumor cells (up to 30%), but overall cellularity still high
- Grade 3: An estimated 30 to 90% reduction in the number of tumor cells
- Grade 4: Marked disappearance of tumor cells such that only small clusters or widely dispersed individual cells remain (loss of greater than 90% of tumor cells)
- Grade 5: No invasive cancer cells identifiable in sections from the site of the tumor (carcinoma in situ may be present)
References
- Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003 Oct;12(5):320-7. link to original article PubMed
Residual cancer burden (RCB)
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- The RCB is calculated as follows: RCB = 1.4 (finv*dprim)0.17 + [4(1 - 0.75LN)dmet]0.17
- where dprim is derived from the bidimensional diameters of the primary tumor bed in the resected specimen, finv is the proportion of the primary tumor bed that contains invasive carcinoma, LN is the number of axillary lymph nodes containing metastatic carcinoma, and dmet is the diameter of the largest metastasis in an axillary lymph node.
- The cut-off points are 1.36 and 3.28.
References
- Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007 Oct 1;25(28):4414-22. Epub 2007 Sep 4. link to original article PubMed
Residual disease in breast and nodes (RDBN)
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- Level 1: pCR in breast and nodes with or without in situ carcinoma
- Levels 2 to 4: Residual disease, calculated as 0.2 (residual breast tumor size in cm) + index of involved nodes (0 for no positive nodes, 1 for 1 to 4 positive nodes, 2 for 5 to 7 positive nodes, and 3 for 8 positive nodes) + the Scarff–Bloom–Richardson grade (1, 2, or 3). The cut-off points are 3 and 4.3.
References
- Chollet P, Abrial C, Durando X, Thivat E, Tacca O, Mouret-Reynier MA, Leheurteur M, Kwiatkowski F, Dauplat J, Penault-Llorca F. A new prognostic classification after primary chemotherapy for breast cancer: residual disease in breast and nodes (RDBN). Cancer J. 2008 Mar-Apr;14(2):128-32. link to original article PubMed
Sataloff's classification
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- Breast:
- T-A: Total or nearly total therapeutic effect
- T-B: Greater than 50% therapeutic effect
- T-C: Less than 50% therapeutic effect
- T-D: No therapeutic effect
- Lymph node:
- N-A: Therapeutic effect but no metastasis
- N-B: No metastasis, no therapeutic effect
- N-C: Therapeutic effect but metastasis
- N-D: Metastasis, no therapeutic effect
References
- Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995 Mar;180(3):297-306. PubMed
Tumor response ratio
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Calculated as follows: Residual breast disease observed upon pathologic examination divided by the size of the tumor on the pre-neoadjuvant therapy image.
- TRR = 0: pathologic complete response (pCR)
- TRR greater than 0 up to 0.4: strong partial response
- TRR greater than 0.4 up to 1.0: weak partial response (WPR)
- TRR greater than 1.0: tumor growth
References
- Miller M, Ottesen RA, Niland JC, Kruper L, Chen SL, Vito C. Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2014 Oct;21(10):3317-23. Epub 2014 Jul 25. link to original article PubMed
ypTNM staging
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This system is proprietary to the AJCC. Please visit their site or consult the AJCC Manual for further details.
Adjuvant chemotherapy
AC
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AC: Adriamycin (Doxorubicin) and Cyclophosphamide
CA: Cyclophosphamide and Adriamycin (Doxorubicin)
Variant #1, 54/1200 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Linden et al. 2007 (INT-0137) | Phase III (C) | A, then C | Seems not superior |
Preceding treatment
Chemotherapy
- Doxorubicin (Adriamycin) 54 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Variant #2, 60/600 x 4
Patients in Van Pelt et al. 2003, NSABP B-31, NCCTG N9831, and BCIRG 006 were HER2-positive.
Preceding treatment
- Most protocols: Surgery
- Van Pelt et al. 2003: Neoadjuvant TH, then surgery
- INT 0148/CALGB 9344: Surgery, within 84 days
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- NSABP B-23: Tamoxifen x 5 y versus placebo
- Içli et al. 2001: EP x 2 versus no further treatment
- Van Pelt et al. 2003: H x 12 mo
- INT 0148/CALGB 9344 and NSABP B-28: q3wk T (Taxol) x 4 versus no further therapy
- CALGB 9741, NCIC CTG MA.21, Loesch et al. 2010: q3wk T (Taxol) x 4
- NSABP B-31: weekly T (Taxol) x 12 versus TH (Taxol) x 12 mo
- IBCSG 13-93: CMF x 3, then Tamoxifen x 5 y versus no further treatment
- NCCTG N9831: weekly T (Taxol) x 12 versus sequential weekly T (Taxol) x 12, then H x 12 mo versus concurrent TH (Taxol) x 12 mo
- BIG 02-98: CMF x 3
- ECOG E1199: q3wk T (Taxotere) x 4 versus weekly T (Taxotere) x 12 versus q3wk T (Taxol) x 4 versus weekly T (Taxol) x 12
- NSABP B-30 & BCIRG-005: q3wk T (Taxotere) x 4
- BCIRG 006: q3wk T (Taxotere) x 4 versus TH (Taxotere) x 12 mo
- NSAS BC-02: q3wk T (Taxotere) x 4 versus T (Taxol) q3wk x 4
- ECOG E5103: weekly T (Taxol) x 12
Variant #3, with range
Study | Evidence |
---|---|
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Patients in APHINITY had HER2-positive breast cancer. Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- TH (Taxol) versus THP (Taxol) or TH (Taxotere) versus THP (Taxotere)
References
- NSABP B-22: Fisher B, Anderson S, Wickerham DL, DeCillis A, Dimitrov N, Mamounas E, Wolmark N, Pugh R, Atkins JN, Meyers FJ, Abramson N, Wolter J, Bornstein RS, Levy L, Romond EH, Caggiano V, Grimaldi M, Jochimsen P, Deckers P. Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22. J Clin Oncol. 1997 May;15(5):1858-69. link to original article contains verified protocol PubMed
- 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
- NSABP B-18: Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB Jr, Fisher ER, Wickerham DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NV. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997 Jul;15(7):2483-93. link to original article contains verified protocol PubMed
- Update: Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. link to original article PubMed
- Update: Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst. 2001;(30):96-102. PubMed
- 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
- Pooled update: Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. link to original article PubMed
- NSABP B-23: Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. link to original article PubMed
- Içli F, Akbulut H, Dinçol D, Onur H, Demirkazik A, Cam R, Cay F, Demirci S, Uner A, Erekul S. A randomized trial of four cycles of adjuvant AC (adriamycin + cyclophosphamide) +/- two cycles of EP (etoposide + cisplatin) in node positive patients with breast cancer. Ann Oncol. 2001 Jul;12(7):1011-3. link to original article contains protocol PubMed
- 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
- 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
- Van Pelt AE, Mohsin S, Elledge RM, Hilsenbeck SG, Gutierrez MC, Lucci A Jr, Kalidas M, Granchi T, Scott BG, Allred DC, Chang JC. Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results. Clin Breast Cancer. 2003 Dec;4(5):348-53. link to original article PubMed
- 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
- RAPP-01: Brain EG, Bachelot T, Serin D, Kirscher S, Graic Y, Eymard JC, Extra JM, Combe M, Fourme E, Noguès C, Rouëssé J; RAPP-01 Trial Investigators. Life-threatening sepsis associated with adjuvant doxorubicin plus docetaxel for intermediate-risk breast cancer. JAMA. 2005 May 18;293(19):2367-71. link to original article contains protocol PubMed
- NSABP B-31/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
- Update: Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011 Sep 1;29(25):3366-73. Epub 2011 Jul 18. link to original article link to PMC article PubMed
- 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
- 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
- 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
- IBCSG 13-93: Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiglione-Gertsch M, Price KN, Coates AS, Gelber RD; International Breast Cancer Study Group. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol. 2006 Mar 20;24(9):1332-41. Epub 2006 Feb 27. link to original article contains verified protocol PubMed
- US Oncology Trial 9735: Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006 Dec 1;24(34):5381-7. Erratum in: J Clin Oncol. 2007 May 1;25(13):1819. link to original article contains protocol PubMed
- Update: Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology research trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83. Epub 2009 Feb 9. link to original article PubMed
- INT-0137: Linden HM, Haskell CM, Green SJ, Osborne CK, Sledge GW Jr, Shapiro CL, Ingle JN, Lew D, Hutchins LF, Livingston RB, Martino S. Sequenced compared with simultaneous anthracycline and cyclophosphamide in high-risk stage I and II breast cancer: final analysis from INT-0137 (S9313). J Clin Oncol. 2007 Feb 20;25(6):656-61. link to original article contains protocol PubMed
- BIG 02-98: Francis P, Crown J, Di Leo A, Buyse M, Balil A, Andersson M, Nordenskjöld B, Lang I, Jakesz R, Vorobiof D, Gutiérrez J, van Hazel G, Dolci S, Jamin S, Bendahmane B, Gelber RD, Goldhirsch A, Castiglione-Gertsch M, Piccart-Gebhart M; BIG 02-98 Collaborative Group. Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial. J Natl Cancer Inst. 2008 Jan 16;100(2):121-33. Epub 2008 Jan 8. Erratum in: J Natl Cancer Inst. 2008 Nov 19;100(22):1655. link to original article contains protocol PubMed
- Update: Oakman C, Francis PA, Crown J, Quinaux E, Buyse M, De Azambuja E, Margeli Vila M, Andersson M, Nordenskjöld B, Jakesz R, Thürlimann B, Gutiérrez J, Harvey V, Punzalan L, Dell'orto P, Larsimont D, Steinberg I, Gelber RD, Piccart-Gebhart M, Viale G, Di Leo A. Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer--8-year results of the Breast International Group 02-98 phase III trial. Ann Oncol. 2013 May;24(5):1203-11. Epub 2013 Jan 4. link to original article PubMed
- Update: Sonnenblick A, Francis PA, Azim HA Jr, de Azambuja E, Nordenskjöld B, Gutiérez J, Quinaux E, Mastropasqua MG, Ameye L, Anderson M, Lluch A, Gnant M, Goldhirsch A, Di Leo A, Barnadas A, Cortes-Funes H, Piccart M, Crown J. Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer. Eur J Cancer. 2015 Aug;51(12):1481-9. Epub 2015 Jun 11. link to original article PubMed
- 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
- 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
- ECOG E2197: Goldstein LJ, O'Neill A, Sparano JA, Perez EA, Shulman LN, Martino S, Davidson NE. Concurrent doxorubicin plus docetaxel is not more effective than concurrent doxorubicin plus cyclophosphamide in operable breast cancer with 0 to 3 positive axillary nodes: North American Breast Cancer Intergroup Trial E 2197. J Clin Oncol. 2008 Sep 1;26(25):4092-9. Epub 2008 Aug 4. link to original article link to PMC article contains protocol PubMed
- Loesch D, Greco FA, Senzer NN, Burris HA, Hainsworth JD, Jones S, Vukelja SJ, Sandbach J, Holmes F, Sedlacek S, Pippen J, Lindquist D, McIntyre K, Blum JL, Modiano MR, Boehm KA, Zhan F, Asmar L, Robert N. Phase III multicenter trial of doxorubicin plus cyclophosphamide followed by paclitaxel compared with doxorubicin plus paclitaxel followed by weekly paclitaxel as adjuvant therapy for women with high-risk breast cancer. J Clin Oncol. 2010 Jun 20;28(18):2958-65. Epub 2010 May 17. link to original article contains protocol PubMed
- NSABP B-30: Swain SM, Jeong JH, Geyer CE Jr, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff J, Vogel VG, Erban JK, Rastogi P, Livingston RB, Perez EA, Mamounas EP, Land SR, Ganz PA, Wolmark N. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med. 2010 Jun 3;362(22):2053-65. link to original article link to PMC article contains verified protocol PubMed
- CALGB 49907: Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Becker HP, Kartcheske PA, Wheeler JD, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Magrinat G, Parker BA, Hart RD, Grenier D, Norton L, Hudis CA, Winer EP; CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009 May 14;360(20):2055-65. Erratum in: N Engl J Med. 2009 Oct 22;361(17):1714. Magrinat, Gutav [corrected to Magrinat, Gustav]. link to original article link to PMC article contains verified protocol PubMed
- 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
- BCIRG-005: Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martín M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press M, Sauter G, Lindsay MA, Riva A, Buyse M, Drevot P, Taupin H, Mackey JR. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011 Oct 10;29(29):3877-84. Epub 2011 Sep 12. link to original article contains verified protocol PubMed
- Update: Mackey JR, Pieńkowski T, Crown J, Sadeghi S, Martín M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press MF, Sauter G, Lindsay M, Houé V, Buyse M, Drevot P, Hitier S, Bensfia S, Eiermann W; Translational Research In Oncology (TRIO)/ Breast Cancer International Research Group (BCIRG)-005 investigators. Long-term outcomes after adjuvant treatment of sequential versus combination docetaxel with doxorubicin and cyclophosphamide in node-positive breast cancer: BCIRG-005 randomized trial. Ann Oncol. 2016 Jun;27(6):1041-7. Epub 2016 Mar 2. link to original article PubMed
- BCIRG 006: Slamon D, Eiermann W, Robert N, Pienkowski T, Martín M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. link to original article link to PMC article PubMed
- NSAS BC-02: Watanabe T, Kuranami M, Inoue K, Masuda N, Aogi K, Ohno S, Iwata H, Mukai H, Uemura Y, Ohashi Y. Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study. Cancer. 2017 Mar 1;123(5):759-768. Epub 2017 Jan 12. link to original article contains protocol PubMed
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
- ECOG E5103: Miller KD, O'Neill A, Gradishar W, Hobday TJ, Goldstein LJ, Mayer IA, Bloom S, Brufsky AM, Tevaarwerk AJ, Sparano JA, Le-Lindqwister NA, Hendricks CB, Northfelt DW, Dang CT, Sledge GW Jr. Double-blind phase III trial of adjuvant chemotherapy with and without bevacizumab in patients with lymph node-positive and high-risk lymph node-negative breast cancer (E5103). J Clin Oncol. 2018 Sep 1;36(25):2621-2629. Epub 2018 Jul 24. link to original article refers to ECOG E1199 protocol PubMed
AT (Taxol)
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AT: Adriamycin (Doxorubicin) & Taxol (Paclitaxel)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gianni et al. 2009 (ECTO) | Phase III (E) | See link | See link |
Preceding treatment
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- CMF x 4
References
- ECTO: Gianni L, Baselga J, Eiermann W, Porta VG, Semiglazov V, Lluch A, Zambetti M, Sabadell D, Raab G, Cussac AL, Bozhok A, Martinez-Agulló A, Greco M, Byakhov M, Lopez JJ, Mansutti M, Valagussa P, Bonadonna G. Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol. 2009 May 20;27(15):2474-81. Epub 2009 Mar 30. link to original article contains verified protocol PubMed
Bevacizumab monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bear et al. 2012 (NSABP B-40) | Phase III (E) | See link | See link |
Preceding treatment
- Neoadjuvant AC+Bev x 4, then surgery
Chemotherapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 10 cycles
References
- Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. link to original article link to PMC article PubMed
- Update: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. link to original article link to PMC article PubMed
Capecitabine monotherapy
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Variant #1, 4 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martín et al. 2015 (GEICAM/2003-10) | Phase III (E) | See link | See link |
Cameron et al. 2017 (TACT2) | Phase III (E) | See link | See link |
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
- GEICAM/2003-10: ET x 4
- TACT2: ddE x 4 versus Epirubicin x 4
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1 to 14
21-day cycle for 4 cycles
Variant #2, 6 to 8 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Muss et al. 2009 (CALGB 49907) | Phase III (E) | Physician's choice of: 1. AC x 4 2. CMF x 6 |
Seems to have inferior OS |
Masuda et al. 2017 (CREATE-X) | Phase III (E) | Standard therapy | Superior OS |
Note: patients in CALGB 49907 received a maximum of 6 cycles. All patients in CREATE-X had residual disease at time of surgical resection. Concomitant endocrine therapy was allowed.
Preceding treatment
- CALGB 49907: Surgery
- CREATE-X: Neoadjuvant chemotherapy containing anthracycline, taxane, or both, then surgery
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1 to 14
21-day cycle for 6 to 8 cycles
References
- CALGB 49907: Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Becker HP, Kartcheske PA, Wheeler JD, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Magrinat G, Parker BA, Hart RD, Grenier D, Norton L, Hudis CA, Winer EP; CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009 May 14;360(20):2055-65. Erratum in: N Engl J Med. 2009 Oct 22;361(17):1714. Magrinat, Gutav [corrected to Magrinat, Gustav]. link to original article link to PMC article contains verified protocol PubMed
- GEICAM/2003-10: Martín M, Ruiz Simón A, Ruiz Borrego M, Ribelles N, Rodríguez-Lescure A, Muñoz-Mateu M, González S, Margelí Vila M, Barnadas A, Ramos M, Del Barco Berron S, Jara C, Calvo L, Martínez-Jáñez N, Mendiola Fernández C, Rodríguez CA, Martínez de Dueñas E, Andrés R, Plazaola A, de la Haba-Rodríguez J, López-Vega JM, Adrover E, Ballesteros AI, Santaballa A, Sánchez-Rovira P, Baena-Cañada JM, Casas M, del Carmen Cámara M, Carrasco EM, Lluch A. Epirubicin plus cyclophosphamide followed by docetaxel versus epirubicin plus docetaxel followed by capecitabine as adjuvant therapy for node-positive early breast cancer: results from the GEICAM/2003-10 study. J Clin Oncol. 2015 Nov 10;33(32):3788-95. Epub 2015 Sep 28. link to original article contains verified protocol PubMed
- CREATE-X: Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, Kuroi K, Im SA, Park BW, Kim SB, Yanagita Y, Ohno S, Takao S, Aogi K, Iwata H, Jeong J, Kim A, Park KH, Sasano H, Ohashi Y, Toi M. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017 Jun 1;376(22):2147-2159. link to original article contains verified protocol PubMed
- TACT2: Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, Agrawal R, Banerji J, Bertelli G, Bloomfield D, Brunt AM, Earl H, Ellis P, Gaunt C, Gillman A, Hearfield N, Laing R, Murray N, Couper N, Stein RC, Verrill M, Wardley A, Barrett-Lee P, Bliss JM; TACT2 Investigators. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2017 Jul;18(7):929-945. Epub 2017 Jun 7. link to original article link to PMC article contains verified protocol PubMed
CMF
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CMF: Cyclophosphamide, Methotrexate, Fluorouracil
Variant #1, 600/40/600 x 8
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Buzzoni et al. 1991 (Milan trial) | Phase III (E) | See link | See link |
Overgaard et al. 1997 (DBCG 82b) | Phase III (E) | See link | See link |
Note: in DBCG 82b, radiotherapy was given between cycles 1 & 2
Preceding treatment
- Milan trial: Surgery, then A x 4
- DBCG 82b: Mastectomy
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Methotrexate (MTX) 40 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
28-day cycle for 8 cycles
Variant #2, 600/50/600 x 8
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Leonard et al. 2004 | Phase III (C) | Cyclophosphamide & Thiotepa with auto HSCT | 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.
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Methotrexate (MTX) 50 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
28-day cycle for 8 cycles
Variant #3, 700/30/700 x 24
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Clahsen et al. 1995 | Phase III (E) | Observation | Seems to have superior OS |
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 50 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 15 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 350 mg/m2 IV once per day on days 1 & 8
Monthly cycle for 24 cycles (2 years)
Variant #4, 750/50/600 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Poole et al. 2006 (BR9601) | Phase III (E) | See link | See link |
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
- E x 4
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Methotrexate (MTX) 50 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Variant #5, 750/50/600 x 8
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Stewart et al. 1993 | Phase III (C) | 1. CMFP 2. Oopherectomy 3. Oopherectomy & Prednisolone |
Seems not superior |
Poole et al. 2006 (BR9601) | Phase III (C) | Epirubicin, then CMF x 4 | Inferior OS |
Note: after 1984, patients in Stewart et al. 1993 only received 6 cycles.
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Methotrexate (MTX) 50 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
21-day cycle for 8 cycles (see note)
Variant #6, 1000/80/1000 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kimura et al. 2009 | Phase III (C) | FEC | Seems not superior |
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days 1 & 8
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
Variant #7, 1000/80/1200 x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Zander et al. 2004 | Phase III (C) | Cyclophosphamide, Mitoxantrone, Thiotepa with auto HSCT | Might have inferior EFS |
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
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days 1 & 8
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 3 cycles
Variant #8, 1000/80/1200 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Jonat et al. 2002 (ZEBRA) | Phase III (C) | Goserelin x 2 y | Seems not superior |
Schmid et al. 2007 (TABLE) | Phase III (C) | Leuprolide | Inferior OS |
Preceding treatment
- Surgery, within 6 weeks
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days 1 & 8
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
Variant #9, 1120/60/1000 x 12
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brinker et al. 1983 (DBCG 77B) | Phase III (E) | 1. Cyclophosphamide | Seems not superior |
2. Levamisole | Not reported | ||
3. No chemotherapy | Seems to have superior OS (*) |
Note: reported efficacy is based on the 2010 update.
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 80 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 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
1-month cycle for 12 cycles
Variant #10, 1120/64/960 x 12
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Howell et al. 1984 | Phase III (E) | Observation | Seems to have superior RFS |
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 80 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 32 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 4800 mg/m2 IV once per day on days 1 & 8
28-day cycle for 12 cycles
Variant #11, 1200/80/1200 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Poole et al. 2006 (NEAT) | Phase III (E) | See link | See link |
Gianni et al. 2009 (ECTO) | Phase III (C) | See link | See link |
Ellis et al. 2009 (TACT) | Randomized Phase II (C) | See link | See link |
Perrone et al. 2014 (ELDA) | Phase III (C) | Docetaxel | Seems not superior |
Cameron et al. 2017 (TACT2) | Phase III (C) | See link | See link |
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. In ELDA, this protocol was for ER/PR+ patients.
Preceding treatment
- NEAT, TACT, TACT2: Surgery, then E x 4
- ECTO: Surgery, then A x 4 versus AT (Taxol) x 4
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once per day on days 1 & 8
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 4 cycles
Variant #12, 1200/80/1200 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Coombes et al. 1996 | Phase III (C) | FEC | Seems not superior |
Ragaz et al. 1997 | Phase III (C) | CMF & RT | Seems to have inferior OS |
Poole et al. 2006 (NEAT) | Phase III (C) | Epirubicin, then CMF x 4 | Inferior OS |
Perrone et al. 2014 (ELDA) | Phase III (C) | Docetaxel | Seems not superior |
Note: In ELDA, this protocol was for ER/PR- patients.
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once per day on days 1 & 8
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
Variant #13, 1400/80/1000 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Watanabe et al. 2009 (NSAS BC-01) | Phase III (C) | UFT | Seems not superior |
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
Variant #14, 1400/80/1200 x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Castiglione-Gertsch et al. 1996 (IBCSG VI) | Phase III (E) | 1. CMF x 6 | Seems to have inferior DFS |
2. CMF x 3, with re-introduction 3. CMF x 6, with re-introduction |
Might have inferior DFS | ||
Colleoni et al. 2006 (IBCSG 13-93) | Non-randomized portion of RCT |
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 3 cycles
Subsequent treatment
- IBCSG VI: Tamoxifen x 5 y versus no further treatment
Variant #15, 1400/80/1200 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Poole et al. 2006 (NEAT) | Phase III (E) | See link | See link |
Cameron et al. 2017 (TACT2) | Phase III (C) | See link | See link |
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
- E x 4
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 4 cycles
Variant #16, 1400/80/1200 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Tancini et al. 1979 | Phase III (E) | CMF x 12 | Seems not superior |
Coombes et al. 1996 | Phase III (C) | FEC | Seems not superior |
Castiglione-Gertsch et al. 1996 (IBCSG VI) | Phase III (C) | 1. CMF x 3 | Seems to have superior DFS |
2. CMF x 3, with re-introduction 3. CMF x 6, with re-introduction |
Might have inferior DFS | ||
Levine et al. 1998 (NCIC CTG MA.5) | Phase III (C) | CEF | Inferior RFS |
Amadori et al. 2000 | Phase III (E) | Observation | Seems to have superior DFS |
Fisher et al. 2001 (NSABP B-23) | Phase III (C) | AC | Seems not superior |
Piccart et al. 2001 (Belgian trial) | Phase III (C) | 1. Full-dose EC | Seems not superior |
2. Moderate-dose EC | Seems not superior | ||
Jonat et al. 2002 (ZEBRA) | Phase III (C) | Goserelin x 2 y | Seems not superior |
Hutchins et al. 2005 (INT-0102) | Phase III (C) | CAF | Seems to have inferior OS |
Poole et al. 2006 (NEAT) | Phase III (C) | Epirubicin, then CMF x 4 | Inferior OS |
Muss et al. 2009 (CALGB 49907) | Phase III (C) | Capecitabine | Seems to have superior OS |
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
Subsequent treatment
Variant #17, 1400/80/1200 x 12
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bonadonna et al. 1976 | Phase III (E) | Observation | Superior RFS |
Tancini et al. 1979 | Phase III (C) | CMF x 6 | Seems not superior |
Misset et al. 1996 (OncoFrance) | Phase III (C) | AVCF | Inferior OS |
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 12 cycles
References
- 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 contains verified protocol PubMed
- 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
- 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
- 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
- Tancini G, Bajetta E, Marchini S, Valagussa P, Bonadonna G, Veronesi U. Preliminary 3-year results of 12 versus 6 cycles of surgical adjuvant CMF in premenopausal breast cancer. Cancer Clin Trials. 1979 Winter;2(4):285-92. PubMed
- Update: Tancini G, Bonadonna G, Valagussa P, Marchini S, Veronesi U. Adjuvant CMF in breast cancer: comparative 5-year results of 12 versus 6 cycles. J Clin Oncol. 1983 Jan;1(1):2-10. link to original article PubMed
- 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
- 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
- Howell A, Bush H, George WD, Howat JM, Crowther D, Sellwood RA, Rubens RD, Hayward JL, Bulbrook RD, Fentiman IS, Chaudary M. Controlled trial of adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil for breast cancer. Lancet. 1984 Aug 11;2(8398):307-11. link to original article PubMed
- Milan trial: Buzzoni R, Bonadonna G, Valagussa P, Zambetti M. Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil in the treatment of resectable breast cancer with more than three positive axillary nodes. J Clin Oncol. 1991 Dec;9(12):2134-40. link to original article PubMed
- Update: Bonadonna G, Zambetti M, Valagussa P. Sequential or alternating doxorubicin and CMF regimens in breast cancer with more than three positive nodes: ten-year results. JAMA. 1995 Feb 15;273(7):542-7. link to original article PubMed
- Stewart HJ, Forrest APM, Hawkins RA, Prescott RJ, Smith DC, Everington D, Richards MA, George WD; Scottish Cancer Trials Breast Group and ICRF Breast Unit Guy's Hospital London. Adjuvant ovarian ablation versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: the Scottish trial. Lancet. 1993 May 22;341(8856):1293-8. link to SD article contains verified protocol PubMed
- Clahsen PC, van de Velde CJ, Welvaart K, van Driel OJ, Sylvester RJ. Ten-year results of a randomized trial evaluating prolonged low-dose adjuvant chemotherapy in node-positive breast cancer: a joint European Organization for Research and Treatment of Cancer-Dutch Breast Cancer Working Party Study. Cooperating Investigators. J Clin Oncol. 1995 Jan;13(1):33-41. link to original article contains protocol PubMed
- Coombes RC, Bliss JM, Wils J, Morvan F, Espié M, Amadori D, Gambrosier P, Richards M, Aapro M, Villar-Grimalt A, McArdle C, Pérez-López FR, Vassilopoulos P, Ferreira EP, Chilvers CE, Coombes G, Woods EM, Marty M; The International Collaborative Cancer Group. Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. J Clin Oncol. 1996 Jan;14(1):35-45. link to original article contains verified protocol PubMed
- OncoFrance: Misset JL, di Palma M, Delgado M, Plagne R, Chollet P, Fumoleau P, Le Mevel B, Belpomme D, Guerrin J, Fargeot P, Metz R, Ithzaki M, Hill C, Mathé G. Adjuvant treatment of node-positive breast cancer with cyclophosphamide, doxorubicin, fluorouracil, and vincristine versus cyclophosphamide, methotrexate, and fluorouracil: final report after a 16-year median follow-up duration. J Clin Oncol. 1996 Apr;14(4):1136-45. link to original article contains verified protocol PubMed
- IBCSG VI: Castiglione-Gertsch M, Goldhirsch A; International Breast Cancer Study Group. Duration and reintroduction of adjuvant chemotherapy for node-positive premenopausal breast cancer patients. J Clin Oncol. 1996 Jun;14(6):1885-94. link to original article contains verified protocol PubMed
- Pooled QoL analysis: Hürny C, Bernhard J, Coates AS, Castiglione-Gertsch M, Peterson HF, Gelber RD, Forbes JF, Rudenstam CM, Simoncini E, Crivellari D, Goldhirsch A, Senn HJ; International Breast Cancer Study Group. Impact of adjuvant therapy on quality of life in women with node-positive operable breast cancer. Lancet. 1996 May 11;347(9011):1279-84. Erratum in: Lancet 1997 Jul 26;350(9073):298. link to original article PubMed
- DBCG 82b: Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy: Danish Breast Cancer Cooperative Group 82b trial. N Engl J Med. 1997 Oct 2;337(14):949-55. link to original article contains verified protocol PubMed
- Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE, Wilson KS, Knowling MA, Coppin CM, Paradis M, Coldman AJ, Olivotto IA. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. 1997 Oct 2;337(14):956-62. link to original article contains protocol PubMed
- Review: Goldhirsch A, Colleoni M, Coates AS, Castiglione-Gertsch M, Gelber RD. Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all CMFs alike? The International Breast Cancer Study Group (IBCSG). Ann Oncol. 1998 May;9(5):489-93. link to original article contains protocol PubMed
- NCIC CTG MA.5: Levine MN, Bramwell VH, Pritchard KI, Norris BD, Shepherd LE, Abu-Zahra H, Findlay B, Warr D, Bowman D, Myles J, Arnold A, Vandenberg T, MacKenzie R, Robert J, Ottaway J, Burnell M, Williams CK, Tu D; National Cancer Institute of Canada Clinical Trials Group. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. J Clin Oncol. 1998 Aug;16(8):2651-8. link to original article PubMed
- Update: Levine MN, Pritchard KI, Bramwell VH, Shepherd LE, Tu D, Paul N; National Cancer Institute of Canada Clinical Trials Group. 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 Aug 1;23(22):5166-70. link to original article PubMed
- Subgroup analysis: Pritchard KI, Shepherd LE, O'Malley FP, Andrulis IL, Tu D, Bramwell VH, Levine MN; National Cancer Institute of Canada Clinical Trials Group. HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med. 2006 May 18;354(20):2103-11. link to original article PubMed
- Amadori D, Nanni O, Marangolo M, Pacini P, Ravaioli A, Rossi A, Gambi A, Catalano G, Perroni D, Scarpi E, Giunchi DC, Tienghi A, Becciolini A, Volpi A. Disease-free survival advantage of adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with node-negative, rapidly proliferating breast cancer: a randomized multicenter study. J Clin Oncol. 2000 Sep;18(17):3125-34. link to original article contains verified protocol PubMed
- Update: Amadori D, Nanni O, Volpi A, Casadei Giunchi D, Marangolo M, Livi L, Ravaioli A, Rossi AP, Gambi A, Luzi Fedeli S, Perroni D, Scarpi E, Becciolini A, Silvestrini R. Phase III randomized multicenter study on the effects of adjuvant CMF in patients with node-negative, rapidly proliferating breast cancer: twelve-year results and retrospective subgroup analysis. Breast Cancer Res Treat. 2008 Mar;108(2):259-64. Epub 2007 May 26. link to original article PubMed
- NSABP B-23: Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. link to original article PubMed
- 'Belgian trial: Piccart MJ, Di Leo A, Beauduin M, Vindevoghel A, Michel J, Focan C, Tagnon A, Ries F, Gobert P, Finet C, Closon-Dejardin MT, Dufrane JP, Kerger J, Liebens F, Beauvois S, Bartholomeus S, Dolci S, Lobelle JP, Paesmans M, Nogaret JM. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001 Jun 15;19(12):3103-10. link to original article PubMed
- Update: de Azambuja E, Paesmans M, Beauduin M, Vindevoghel A, Cornez N, Finet C, Ries F, Closon-Dejardin MT, Kerger J, Gobert P, Focan C, Tagnon A, Dolci S, Nogaret JM, di Leo A, Piccart-Gebhart MJ. Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node-positive breast cancer: 15-year efficacy results of the Belgian multicentre study. J Clin Oncol. 2009 Feb 10;27(5):720-5. Epub 2008 Dec 22. link to original article PubMed
- ZEBRA: Jonat W, Kaufmann M, Sauerbrei W, Blamey R, Cuzick J, Namer M, Fogelman I, de Haes JC, de Matteis A, Stewart A, Eiermann W, Szakolczai I, Palmer M, Schumacher M, Geberth M, Lisboa B; Zoladex Early Breast Cancer Research Association Study. Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study. J Clin Oncol. 2002 Dec 15;20(24):4628-35. link to original article contains verified protocol PubMed
- Zander AR, Kröger N, Schmoor C, Krüger W, Möbus V, Frickhofen N, Metzner B, Schultze W, Berdel WE, Koenigsmann M, Thiel E, Wandt H, Possinger K, Trümper L, Kreienberg R, Carstensen M, Schmidt EH, Jänicke F, Schumacher M, Jonat W. High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: first results of a randomized trial. J Clin Oncol. 2004 Jun 15;22(12):2273-83. Epub 2004 Apr 26. link to original article contains protocol PubMed
- Leonard RC, Lind M, Twelves C, Coleman R, van Belle S, Wilson C, Ledermann J, Kennedy I, Barrett-Lee P, Perren T, Verrill M, Cameron D, Foster E, Yellowlees A, Crown J; Anglo-Celtic Cooperative Oncology Group. Conventional adjuvant chemotherapy versus single-cycle, autograft-supported, high-dose, late-intensification chemotherapy in high-risk breast cancer patients: a randomized trial. J Natl Cancer Inst. 2004 Jul 21;96(14):1076-83. link to original article contains protocol PubMed
- INT-0102: Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. 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 Nov 20;23(33):8313-21. link to original article PubMed
- IBCSG 13-93: Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiglione-Gertsch M, Price KN, Coates AS, Gelber RD; International Breast Cancer Study Group. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol. 2006 Mar 20;24(9):1332-41. Epub 2006 Feb 27. link to original article contains verified protocol PubMed
- NEAT/BR9601: Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. link to original article PubMed
- Update: Earl HM, Hiller L, Dunn JA, Vallier AL, Bowden SJ, Jordan SD, Blows F, Munro A, Bathers S, Grieve R, Spooner DA, Agrawal R, Fernando I, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, McAdam K, Foster L, Leonard RC, Twelves CJ, Cameron D, Bartlett JM, Pharoah P, Provenzano E, Caldas C, Poole CJ; NEAT Investigators and the SCTBG. Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials. Br J Cancer. 2012 Oct 9;107(8):1257-67. Epub 2012 Sep 11. link to original article link to PMC article PubMed
- Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Cold S, Edlund P, Ewertz M, Jensen BB, Kamby C, Nordenskjold B, Bergh J. Improved outcome from substituting methotrexate with epirubicin: results from a randomised comparison of CMF versus CEF in patients with primary breast cancer. Eur J Cancer. 2007 Mar;43(5):877-84. Epub 2007 Feb 16. link to original article PubMed
- TABLE: Schmid P, Untch M, Kossé V, Bondar G, Vassiljev L, Tarutinov V, Lehmann U, Maubach L, Meurer J, Wallwiener D, Possinger K. Leuprorelin acetate every-3-months depot versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant treatment in premenopausal patients with node-positive breast cancer: the TABLE study. J Clin Oncol. 2007 Jun 20;25(18):2509-15. link to original article contains verified protocol PubMed
- NSAS BC-01: Watanabe T, Sano M, Takashima S, Kitaya T, Tokuda Y, Yoshimoto M, Kohno N, Nakagami K, Iwata H, Shimozuma K, Sonoo H, Tsuda H, Sakamoto G, Ohashi Y. Oral uracil and tegafur compared with classic cyclophosphamide, methotrexate, fluorouracil as postoperative chemotherapy in patients with node-negative, high-risk breast cancer: National Surgical Adjuvant Study for Breast Cancer 01 trial. J Clin Oncol. 2009 Mar 20;27(9):1368-74. Epub 2009 Feb 9. link to original article contains verified protocol PubMed
- ECTO: Gianni L, Baselga J, Eiermann W, Porta VG, Semiglazov V, Lluch A, Zambetti M, Sabadell D, Raab G, Cussac AL, Bozhok A, Martinez-Agulló A, Greco M, Byakhov M, Lopez JJ, Mansutti M, Valagussa P, Bonadonna G. Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol. 2009 May 20;27(15):2474-81. Epub 2009 Mar 30. link to original article contains verified protocol PubMed
- TACT: Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. link to original article link to PMC article contains protocol PubMed
- CALGB 49907: Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Becker HP, Kartcheske PA, Wheeler JD, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Magrinat G, Parker BA, Hart RD, Grenier D, Norton L, Hudis CA, Winer EP; CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009 May 14;360(20):2055-65. Erratum in: N Engl J Med. 2009 Oct 22;361(17):1714. Magrinat, Gutav [corrected to Magrinat, Gustav]. link to original article link to PMC article contains verified protocol PubMed
- Kimura M, Tominaga T, Takatsuka Y, Toi M, Abe R, Koyama H, Takashima S, Nomura Y, Miura S, Kimijima I, Tashiro H, Ohashi Y; Adjuvant CEF Research Group for Breast Cancer. Randomized trial of cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil with node-positive breast cancer in Japan. Breast Cancer. 2010 Jul;17(3):190-8. Epub 2009 Jul 3. link to original article contains protocol PubMed
- ELDA: Perrone F, Nuzzo F, Di Rella F, Gravina A, Iodice G, Labonia V, Landi G, Pacilio C, Rossi E, De Laurentiis M, D'Aiuto M, Botti G, Forestieri V, Lauria R, De Placido S, Tinessa V, Daniele B, Gori S, Colantuoni G, Barni S, Riccardi F, De Maio E, Montanino A, Morabito A, Daniele G, Di Maio M, Piccirillo MC, Signoriello S, Gallo C, de Matteis A. Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial. Ann Oncol. 2015 Apr;26(4):675-82. Epub 2014 Dec 8. link to original article contains protocol PubMed
- TACT2: Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, Agrawal R, Banerji J, Bertelli G, Bloomfield D, Brunt AM, Earl H, Ellis P, Gaunt C, Gillman A, Hearfield N, Laing R, Murray N, Couper N, Stein RC, Verrill M, Wardley A, Barrett-Lee P, Bliss JM; TACT2 Investigators. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2017 Jul;18(7):929-945. Epub 2017 Jun 7. link to original article link to PMC article contains verified protocol PubMed
CMFT
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CMFT: Cyclophosphamide, Methotrexate, Fluorouracil, Tamoxifen
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Overgaard et al. 1999 (DBCG 82C) | Phase III (E) | 1. Tamoxifen | Superior DFS (*) |
2. Tamoxifen & RT | Not reported |
Note: efficacy for this arm versus tamoxifen monotherapy is based on the 2013 update.
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Methotrexate (MTX) 40 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Tamoxifen (Nolvadex) 30 mg PO once per day
28-day cycle for 9 cycles (tamoxifen continued for one year total)
References
- DBCG 82C: Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, Kamby C, Kjaer M, Gadeberg CC, Rasmussen BB, Blichert-Toft M, Mouridsen HT. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999 May 15;353(9165):1641-8. link to original article contains protocol PubMed
- Update: Ejlertsen B, Jensen MB, Elversang J, Rasmussen BB, Andersson M, Andersen J, Nielsen DL, Cold S, Mouridsen HT. One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer. Eur J Cancer. 2013 Sep;49(14):2986-94. Epub 2013 Jun 8. link to original article contains verified protocol PubMed
DC/TC
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DC: Docetaxel & Cyclophosphamide
TC: Taxotere (Docetaxel) & Cyclophosphamide
Variant #1, 4 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Jones et al. 2006 (US Oncology Trial 9735) | Phase III (E) | AC | Seems to have superior OS |
Blum et al. 2017 (USOR 06-090; NSABP-46-I/USOR 07132; NSABP B-49) | Phase III (C) | TAC | Seems to have inferior IDFS |
Note: Blum et al. 2017 is a pooled analysis of three RCTs, some of which had arms other than TAC and TC. Refer to the paper for further details.
Preceding treatment
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- All cycles given with Filgrastim (Neupogen) support
21-day cycle for 4 cycles
Variant #2, 6 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mavroudis et al. 2016 (HORG CT/07.17) | Phase III (E) | ddFEC, then D | Inconclusive whether non-inferior |
Ejlertsen et al. 2017 (DBCG 07-READ) | Phase III (E) | EC, then D | Seems not superior |
Patients in DBCG 07-READ were TOP2A normal as determined by FISH.
Preceding treatment
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
References
- US Oncology Trial 9735: Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006 Dec 1;24(34):5381-7. Erratum in: J Clin Oncol. 2007 May 1;25(13):1819. link to original article PubMed
- Update: Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83. Epub 2009 Feb 9. link to original article PubMed
- HORG CT/07.17: Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; Breast Cancer Investigators of the Hellenic Oncology Research Group (HORG). Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2016 Oct;27(10):1873-8. Epub 2016 Aug 8. link to original article contains verified protocol PubMed
- USOR 06-090; NSABP-46-I/USOR 07132; NSABP B-49: Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, Robert NJ, Hopkins JO, O'Shaughnessy JA, Dang CT, Gómez HL, Fehrenbacher L, Vukelja SJ, Lyss AP, Paul D, Brufsky AM, Jeong JH, Colangelo LH, Swain SM, Mamounas EP, Jones SE, Wolmark N. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-2655. Epub 2017 Apr 11. link to original article link to PMC article contains verified protocol PubMed
- DBCG 07-READ: Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Højris I, Ewertz M, Balslev E, Danø H, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol. 2017 Aug 10;35(23):2639-2646. Epub 2017 Jun 29. link to original article contains verified protocol PubMed
ddA
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ddA: dose-dense Adriamycin (Doxorubicin)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Citron et al. 2003 (CALGB 9741) | Phase III (E) | See link | See link |
Kahan et al. 2005 | Phase II |
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
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
Supportive medications
14-day cycle for 4 cycles
Subsequent treatment
References
- 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
- Kahan Z, Uhercsak G, Hajnal-Papp R, Boda K, Thurzo L. Dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy is well tolerated and safe in high-risk early breast cancer. Oncology. 2005;68(4-6):446-53. Epub 2005 Jul 13. link to original article PubMed
- Update: Kelemen G, Uhercsák G, Ormándi K, Eller J, Thurzó L, Kahán Z. Long-term efficiency and toxicity of adjuvant dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy in high-risk breast cancer. Oncology. 2010;78(3-4):271-3. Epub 2010 Jun 7. link to original article PubMed
ddAC
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ddAC: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide
Variant #1, 4 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Citron et al. 2003 (CALGB 9741) | Phase III (E) | See link | See link |
Burstein et al. 2005 | Non-randomized | ||
Dang et al. 2008 | Phase II | ||
Shulman et al. 2012 (CALGB 40101) | Phase III (E) | 1. ddAC x 6 | Seems not superior |
2. ddT x 4 | Seems not superior | ||
3. ddT x 6 | Seems not superior | ||
Swain et al. 2013 (NSABP B-38) | Phase III (C) | See link | See link |
Note: CALGB 40101 originally specified 21-day cycles but was amended to 14-day cycles after results of CALGB 9741 were available. Patients in Dang et al. 2008 had HER2-positive breast cancer.
Preceding treatment
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- (varies depending on reference):
- CALGB 9741:
- Filgrastim (Neupogen) 5 mcg/kg (rounded to either 300 or 480 mcg) SC once per day on days 3 to 10
- Note: Citron et al. 2003 says the schedule was "filgrastim days 3 to 10 of each cycle (a total of seven doses)," so it is unclear whether 7 or 8 doses was actually used).
- Filgrastim (Neupogen) 5 mcg/kg (rounded to either 300 or 480 mcg) SC once per day on days 3 to 10
- Burstein et al. 2005 and Dang et al. 2008:
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2, given 24 hours after chemotherapy
- Burstein et al. 2005:
- Darbepoetin alfa (Aranesp) 200 mcg SC once on day 1 for patients with Hb 10 to 12 g/dL; see Burstein et al. 2005 for additional dose adjustments
- CALGB 40101: one of the following:
- Filgrastim (Neupogen) 5 mcg/kg (rounded to 300 mcg or 480 mcg, whichever is closer) SC on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Sargramostim (Leukine) 250 to 500 mcg/m2 SC on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Pegfilgrastim (Neulasta) 6 mg SC, administered once 24 to 36 hours after chemotherapy
14-day cycle for 4 cycles
Subsequent treatment
- CALGB 9741 and Burstein et al. 2005: ddT (Taxol) x 4
- Dang et al. 2008: ddTH (Taxol)
- NSABP B-38: ddT (Taxol) x 4 versus ddPG x 4
Variant #2, 4 cycles, with range
Study | Evidence |
---|---|
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Patients in APHINITY had HER2-positive breast cancer. Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive medications
- G-CSF support (drug/dose/schedule not specified)
14-day cycle for 4 cycles
Subsequent treatment
- TH (Taxol) versus THP (Taxol) or TH (Taxotere) versus THP (Taxotere)
Variant #3, 6 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Budd et al. 2014 (SWOG S0221) | Phase III (C) | Continuous AC | 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.
Preceding treatment
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2
14-day cycle for 6 cycles
Subsequent treatment
References
- 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
- Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. link to original article contains verified protocol PubMed
- Dang C, Fornier M, Sugarman S, Troso-Sandoval T, Lake D, D'Andrea G, Seidman A, Sklarin N, Dickler M, Currie V, Gilewski T, Moynahan ME, Drullinsky P, Robson M, Wasserheit-Leiblich C, Mills N, Steingart R, Panageas K, Norton L, Hudis C. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer. J Clin Oncol. 2008 Mar 10;26(8):1216-22. link to original article contains verified protocol PubMed
- CALGB 40101: Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article contains verified protocol link to study protocol PDF link to PMC article PubMed
- Update: Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. link to PMC article PubMed
- NSABP B-38: Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. Epub 2013 Aug 12. link to original article link to PMC article contains verified protocol PubMed
- SWOG S0221: Budd GT, Barlow WE, Moore HC, Hobday TJ, Stewart JA, Isaacs C, Salim M, Cho JK, Rinn KJ, Albain KS, Chew HK, Burton GV, Moore TD, Srkalovic G, McGregor BA, Flaherty LE, Livingston RB, Lew DL, Gralow JR, Hortobagyi GN. SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. J Clin Oncol. 2015 Jan 1;33(1):58-64. Epub 2014 Nov 24. link to original article contains verified protocol link to PMC article PubMed
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
- ECOG E5103: Miller KD, O'Neill A, Gradishar W, Hobday TJ, Goldstein LJ, Mayer IA, Bloom S, Brufsky AM, Tevaarwerk AJ, Sparano JA, Le-Lindqwister NA, Hendricks CB, Northfelt DW, Dang CT, Sledge GW Jr. Double-blind phase III trial of adjuvant chemotherapy with and without bevacizumab in patients with lymph node-positive and high-risk lymph node-negative breast cancer (E5103). J Clin Oncol. 2018 Sep 1;36(25):2621-2629. Epub 2018 Jul 24. link to original article refers to ECOG E1199 protocol PubMed
ddC
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ddC: dose-dense Cyclophosphamide
Variant #1, 600 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Citron et al. 2003 (CALGB 9741) | Phase III (E) | See link | See link |
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
- ddT x 4
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg (rounded to either 300 or 480 mcg) SC once per day on days 3 to 10
- Note: Citron et al. 2003 says the schedule was "filgrastim days 3 to 10 of each cycle (a total of seven doses)," so it is unclear whether 7 or 8 doses was actually used).
14-day cycle for 4 cycles
Variant #2, 800 mg/m2
Study | Evidence |
---|---|
Kahan et al. 2005 | Phase II |
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
- ddT x 4
Chemotherapy
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV once on day 1
Supportive medications
14-day cycle for 4 cycles
References
- 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
- Kahan Z, Uhercsak G, Hajnal-Papp R, Boda K, Thurzo L. Dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy is well tolerated and safe in high-risk early breast cancer. Oncology. 2005;68(4-6):446-53. Epub 2005 Jul 13. link to original article PubMed
- Update: Kelemen G, Uhercsák G, Ormándi K, Eller J, Thurzó L, Kahán Z. Long-term efficiency and toxicity of adjuvant dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy in high-risk breast cancer. Oncology. 2010;78(3-4):271-3. Epub 2010 Jun 7. link to original article PubMed
ddEC
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ddEC: dose-dense Epirubicin and Cyclophosphamide
Variant #1, 90/600
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Nitz et al. 2005 (MA-01) | Phase III (C) | EC, then ECT with auto HSCT | Seems to have inferior OS |
Del Mastro et al. 2015 (GIM2) | Phase III (E) | See link | See link |
Note: a mid-protocol amendment of GIM2 suggested giving the pegilgrastim at least 72 h after chemotherapy.
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- MA-01: Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 12
- GIM2: Pegfilgrastim (Neulasta) 6 mg SC once on day 2
14-day cycle for 4 cycles
Subsequent treatment
- MA-01: ddCMF x 3
- GIM2: Dose-dense Paclitaxel
Variant #2, 120/830
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Burnell et al. 2009 (NCIC CTG MA.21) | Phase III (E) | See link | See link |
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 830 mg/m2 IV once on day 1
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 13
- Epoetin alfa (Procrit) 40,000 units SC once per week
14-day cycle for 6 cycles
Subsequent treatment
- T (Taxol) x 4
Variant #3, with range
Study | Evidence |
---|---|
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Patients in APHINITY had HER2-positive breast cancer. Note that ranges for ddEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive medications
- G-CSF support (drug/dose/schedule not specified)
14-day cycle for 4 cycles
Subsequent treatment
- TH (Taxol) versus THP (Taxol) or TH (Taxotere) versus THP (Taxotere)
References
- MA-01: Nitz UA, Mohrmann S, Fischer J, Lindemann W, Berdel WE, Jackisch C, Werner C, Ziske C, Kirchner H, Metzner B, Souchon R, Ruffert U, Schütt G, Pollmanns A, Schmoll HJ, Middecke C, Baltzer J, Schrader I, Wiebringhaus H, Ko Y, Rösel S, Schwenzer T, Wernet P, Hinke A, Bender HG, Frick M; West German Study Group. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial. Lancet. 2005 Dec 3;366(9501):1935-44. Erratum in: Lancet. 2006 Mar 4;367(9512):730. link to original article contains verified protocol PubMed
- 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
- 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
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
ddFEC
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ddFEC: dose-dense Fluorouracil, Epirubicin, Cyclophosphamide
Variant #1, 500/75/500
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mavroudis et al. 2016 (HORG CT/07.17) | Phase III (C) | See link | See link |
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
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Supportive medications
- Filgrastim or Pegfilgrastim (Neulasta) support (drug/dose/schedule not specified)
14-day cycle for 4 cycles
Subsequent treatment
Variant #2, 600/90/600
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Del Mastro et al. 2015 (GIM2) | Phase III (E) | See link | See link |
Note: a mid-protocol amendment suggested giving the pegilgrastim at least 72 h after chemotherapy. 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
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2
14-day cycle for 4 cycles
Subsequent treatment
Variant #3, 700/75/700
Study | Evidence |
---|---|
Mavroudis et al. 2015 (HORG CT/04.23) | Non-randomized portion of RCT |
Note: these patients had HER2+ breast cancer. 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
- Fluorouracil (5-FU) 700 mg/m2 IV over 5 to 15 minutes once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV over 5 to 15 minutes once on day 1
- Cyclophosphamide (Cytoxan) 700 mg/m2 IV over 30 to 60 minutes once on day 1
Supportive medications
- Filgrastim (Neupogen) 300 or 480 mcg SC once per day on days 3 to 10
14-day cycle for 4 cycles
Subsequent treatment
- ddTH (Taxotere) x 4
References
- 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
- HORG CT/04.23: Mavroudis D, Saloustros E, Malamos N, Kakolyris S, Boukovinas I, Papakotoulas P, Kentepozidis N, Ziras N, Georgoulias V; Breast Cancer Investigators of Hellenic Oncology Research Group (HORG), Athens, Greece. Six versus 12 months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2015 Jul;26(7):1333-40. Epub 2015 May 1. link to original article contains verified protocol PubMed
- HORG CT/07.17: Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; Breast Cancer Investigators of the Hellenic Oncology Research Group (HORG). Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2016 Oct;27(10):1873-8. Epub 2016 Aug 8. link to original article contains verified protocol PubMed
ddT (Taxotere)
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ddT: dose-dense Taxotere (Docetaxel)
ddD: dose-dense Docetaxel
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Saloustros et al. 2014 | Phase III (E) | ddT (Taxol) | Seems not superior |
Mavroudis et al. 2016 (HORG CT/07.17) | Phase III (C) | See link | See link |
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
- ddFEC x 4
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Supportive medications
- Filgrastim or Pegfilgrastim support (drug/dose/schedule not specified)
14-day cycle for 4 cycles
References
- Saloustros E, Malamos N, Boukovinas I, Kakolyris S, Kouroussis C, Athanasiadis A, Ziras N, Kentepozidis N, Makrantonakis P, Polyzos A, Christophyllakis C, Georgoulias V, Mavroudis D. Dose-dense paclitaxel versus docetaxel following FEC as adjuvant chemotherapy in axillary node-positive early breast cancer: a multicenter randomized study of the Hellenic Oncology Research Group (HORG). Breast Cancer Res Treat. 2014 Dec;148(3):591-7. Epub 2014 Nov 16. link to original article contains protocol PubMed
- HORG CT/07.17: Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; Breast Cancer Investigators of the Hellenic Oncology Research Group (HORG). Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2016 Oct;27(10):1873-8. Epub 2016 Aug 8. link to original article contains verified protocol PubMed
Docetaxel monotherapy
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D: Docetaxel
T: Taxotere (Docetaxel)
dT: doceTaxel
Variant #1, 35 mg/m2 weekly x 12
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sparano et al. 2008 (ECOG E1199) | Phase III (E) | 1. Paclitaxel, q3wk dosing | Seems not superior |
2. Paclitaxel, weekly dosing 3. Docetaxel, q3wk dosing |
Not reported |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- AC x 4
Chemotherapy
- Docetaxel (Taxotere) 35 mg/m2 IV over 60 minutes once per week
12-week course
Variant #2, 75 mg/m2 q3wk x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Watanabe et al. 2017 (NSAS BC-02) | Phase III (C) | See link | See link |
Mavroudis et al. 2017 | Phase III (E) | See link | See link |
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
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
21-day cycle for 4 cycles
Variant #3, 80 mg/m2 q3wk x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Joensuu et al. 2009 (FinXX) | Phase III (C) | See link | See link |
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
- Docetaxel (Taxotere) 80 mg/m2 IV over 60 minutes once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- CEF x 3
Variant #4, 100 mg/m2 q3wk x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Joensuu et al. 2006 (FinHer) | Phase III (C) | 1. TH (Taxotere) 2. VH |
Seems not superior |
3. Vinorelbine | Superior DDFS | ||
Roché et al. 2006 (FNCLCC PACS 01) | Phase III (E) | See link | See link |
Coombes et al. 2011 (DEVA) | Phase III (E) | See link | See link |
Foukakis et al. 2016 (PANTHER) | Phase III (C) | Dose-dense tailored chemotherapy | Seems not superior |
Ejlertsen et al. 2017 (DBCG 07-READ) | Phase III (C) | See link | See link |
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 FinHer without HER2/neu amplification were only randomized to this or the vinorelbine arm. Patients in DBCG 07-READ were TOP2A normal as determined by FISH.
Preceding treatment
- FinHer: Surgery with axillary lymph node dissection or sentinel lymph node biopsy, within 12 weeks
- FNCLCC PACS 01 & PANTHER: Surgery, then FEC x 3
- DEVA: Surgery, then Epirubicin x 3
- DBCG 07-READ: Surgery, then EC x 3
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- FinHer: FEC
Variant #5, 100 mg/m2 q3wk x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bear et al. 2003 (NSABP B-27) | Phase III (E) | See link | See link |
Sparano et al. 2008 (ECOG E1199) | Phase III (E) | 1. Paclitaxel, q3wk dosing | Seems to have superior DFS |
2. Paclitaxel, weekly dosing 3. Docetaxel, weekly dosing |
Not reported | ||
Polyzos et al. 2009 | Phase III (E) | See link | See link |
Ellis et al. 2009 (TACT) | Randomized Phase II (E) | See link | See link |
Swain et al. 2010 (NSABP B-30) | Phase III (E) | See link | See link |
Eiermann et al. 2011 (BCIRG-005) | Phase III (E) | See link | See link |
Slamon et al. 2011 (BCIRG 006) | Phase III (C) | See link | See link |
Martín et al. 2015 (GEICAM/2003-10) | Phase III (C) | See link | See link |
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 BCIRG 006 were HER2-positive.
Preceding treatment
- NSABP B-27: Neoadjuvant AC x 4, then surgery
- ECOG E1199, BCIRG-005, and BCIRG 006: Surgery, then AC x 4
- Polyzos et al. 2009: Surgery
- TACT: Surgery, then FEC x 4
- GEICAM/2003-10: Surgery, then EC x 4
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Polyzos et al. 2009: EC x 4
References
- NSABP B-27: Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N; National Surgical Adjuvant Breast and Bowel Project Protocol B-27. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003 Nov 15;21(22):4165-74. Epub 2003 Oct 14. link to original article contains verified protocol PubMed
- Update: Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006 May 1;24(13):2019-27. Epub 2006 Apr 10. link to original article PubMed
- Pooled update: Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. link to original article PubMed
- FinHer: Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. link to original article contains verified protocol PubMed
- Update: Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. link to original article PubMed
- FNCLCC PACS 01: Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, Symann M, Kerbrat P, Soulié P, Eichler F, Viens P, Monnier A, Vindevoghel A, Campone M, Goudier MJ, Bonneterre J, Ferrero JM, Martin AL, Genève J, Asselain B. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006 Dec 20;24(36):5664-71. Epub 2006 Nov 20. link to original article PubMed
- Update: Coudert B, Asselain B, Campone M, Spielmann M, Machiels JP, Pénault-Llorca F, Serin D, Lévy C, Romieu G, Canon JL, Orfeuvre H, Piot G, Petit T, Jerusalem G, Audhuy B, Veyret C, Beauduin M, Eymard JC, Martin AL, Roché H; UNICANCER Breast Group. Extended benefit from sequential administration of docetaxel after standard fluorouracil, epirubicin, and cyclophosphamide regimen for node-positive breast cancer: the 8-year follow-up results of the UNICANCER-PACS01 trial. Oncologist. 2012;17(7):900-9. Epub 2012 May 18. link to original article link to PMC article PubMed
- 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
- 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
- TACT: Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. link to original article link to PMC article contains verified protocol PubMed
- Polyzos A, Malamos N, Boukovinas I, Adamou A, Ziras N, Kalbakis K, Kakolyris S, Syrigos K, Papakotoulas P, Kouroussis C, Karvounis N, Vamvakas L, Christophyllakis C, Athanasiadis A, Varthalitis I, Georgoulias V, Mavroudis D. FEC versus sequential docetaxel followed by epirubicin/cyclophosphamide as adjuvant chemotherapy in women with axillary node-positive early breast cancer: a randomized study of the Hellenic Oncology Research Group (HORG). Breast Cancer Res Treat. 2010 Jan;119(1):95-104. Epub 2009 Jul 28. link to original article contains protocol PubMed
- FinXX: Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Asola R, Kokko R, Ahlgren J, Auvinen P, Hemminki A, Paija O, Helle L, Nuortio L, Villman K, Nilsson G, Lahtela SL, Lehtiö K, Pajunen M, Poikonen P, Nyandoto P, Kataja V, Bono P, Leinonen M, Lindman H; FinXX Study Investigators. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial. Lancet Oncol. 2009 Dec;10(12):1145-51. Epub 2009 Nov 10. link to original article PubMed
- Update: Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Paija O, Helle L, Villman K, Nyandoto P, Nilsson G, Pajunen M, Asola R, Poikonen P, Leinonen M, Kataja V, Bono P, Lindman H. Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial. J Clin Oncol. 2012 Jan 1;30(1):11-8. Epub 2011 Nov 21. link to original article PubMed
- NSABP B-30: Swain SM, Jeong JH, Geyer CE Jr, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff J, Vogel VG, Erban JK, Rastogi P, Livingston RB, Perez EA, Mamounas EP, Land SR, Ganz PA, Wolmark N. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med. 2010 Jun 3;362(22):2053-65. link to original article link to PMC article contains verified protocol PubMed
- DEVA: Coombes RC, Bliss JM, Espie M, Erdkamp F, Wals J, Tres A, Marty M, Coleman RE, Tubiana-Mathieu N, den Boer MO, Wardley A, Kilburn LS, Cooper D, Thomas MW, Reise JA, Wilkinson K, Hupperets P. Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with node-positive breast cancer. J Clin Oncol. 2011 Aug 20;29(24):3247-54. Epub 2011 Jul 18. link to original article contains protocol PubMed
- BCIRG-005: Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martín M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press M, Sauter G, Lindsay MA, Riva A, Buyse M, Drevot P, Taupin H, Mackey JR. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011 Oct 10;29(29):3877-84. Epub 2011 Sep 12. link to original article contains verified protocol PubMed
- Update: Mackey JR, Pieńkowski T, Crown J, Sadeghi S, Martín M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press MF, Sauter G, Lindsay M, Houé V, Buyse M, Drevot P, Hitier S, Bensfia S, Eiermann W; Translational Research In Oncology (TRIO)/ Breast Cancer International Research Group (BCIRG)-005 investigators. Long-term outcomes after adjuvant treatment of sequential versus combination docetaxel with doxorubicin and cyclophosphamide in node-positive breast cancer: BCIRG-005 randomized trial. Ann Oncol. 2016 Jun;27(6):1041-7. Epub 2016 Mar 2. link to original article PubMed
- BCIRG 006: Slamon D, Eiermann W, Robert N, Pienkowski T, Martín M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. link to original article link to PMC article PubMed
- GEICAM/2003-10: Martín M, Ruiz Simón A, Ruiz Borrego M, Ribelles N, Rodríguez-Lescure A, Muñoz-Mateu M, González S, Margelí Vila M, Barnadas A, Ramos M, Del Barco Berron S, Jara C, Calvo L, Martínez-Jáñez N, Mendiola Fernández C, Rodríguez CA, Martínez de Dueñas E, Andrés R, Plazaola A, de la Haba-Rodríguez J, López-Vega JM, Adrover E, Ballesteros AI, Santaballa A, Sánchez-Rovira P, Baena-Cañada JM, Casas M, del Carmen Cámara M, Carrasco EM, Lluch A. Epirubicin plus cyclophosphamide followed by docetaxel versus epirubicin plus docetaxel followed by capecitabine as adjuvant therapy for node-positive early breast cancer: results from the GEICAM/2003-10 study. J Clin Oncol. 2015 Nov 10;33(32):3788-95. Epub 2015 Sep 28. link to original article contains verified protocol PubMed
- PANTHER: Foukakis T, von Minckwitz G, Bengtsson NO, Brandberg Y, Wallberg B, Fornander T, Mlineritsch B, Schmatloch S, Singer CF, Steger G, Egle D, Karlsson E, Carlsson L, Loibl S, Untch M, Hellström M, Johansson H, Anderson H, Malmström P, Gnant M, Greil R, Möbus V, Bergh J; Swedish Breast Cancer Group (SweBCG), the German Breast Group (GBG), and the Austrian Breast & Colorectal Cancer Study Group (ABCSG). Effect of tailored dose-dense chemotherapy vs standard 3-weekly adjuvant chemotherapy on recurrence-free survival among women with high-risk early breast cancer: a randomized clinical trial. JAMA. 2016 Nov 8;316(18):1888-1896. link to original article contains verified protocol PubMed
- NSAS BC-02: Watanabe T, Kuranami M, Inoue K, Masuda N, Aogi K, Ohno S, Iwata H, Mukai H, Uemura Y, Ohashi Y. Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study. Cancer. 2017 Mar 1;123(5):759-768. Epub 2017 Jan 12. link to original article contains protocol PubMed
- Mavroudis D, Saloustros E, Boukovinas I, Papakotoulas P, Kakolyris S, Ziras N, Christophylakis C, Kentepozidis N, Fountzilas G, Rigas G, Varthalitis I, Kalbakis K, Agelaki S, Hatzidaki D, Georgoulias V. Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group. Br J Cancer. 2017 Jul 11;117(2):164-170. Epub 2017 Jun 22. link to original article contains verified protocol link to PMC article PubMed
- DBCG 07-READ: Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Højris I, Ewertz M, Balslev E, Danø H, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol. 2017 Aug 10;35(23):2639-2646. Epub 2017 Jun 29. link to original article contains verified protocol PubMed
Doxorubicin monotherapy
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A: Adriamycin (Doxorubicin)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Buzzoni et al. 1991 (Milan trial) | Phase III (E) | See link | See link |
Leonard et al. 2004 | Non-randomized portion of RCT | ||
Gianni et al. 2009 (ECTO) | Phase III (C) | See link | See link |
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
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
References
- Milan trial: Buzzoni R, Bonadonna G, Valagussa P, Zambetti M. Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil in the treatment of resectable breast cancer with more than three positive axillary nodes. J Clin Oncol. 1991 Dec;9(12):2134-40. link to original article PubMed
- Update: Bonadonna G, Zambetti M, Valagussa P. Sequential or alternating doxorubicin and CMF regimens in breast cancer with more than three positive nodes: ten-year results. JAMA. 1995 Feb 15;273(7):542-7. link to original article PubMed
- Leonard RC, Lind M, Twelves C, Coleman R, van Belle S, Wilson C, Ledermann J, Kennedy I, Barrett-Lee P, Perren T, Verrill M, Cameron D, Foster E, Yellowlees A, Crown J; Anglo-Celtic Cooperative Oncology Group. Conventional adjuvant chemotherapy versus single-cycle, autograft-supported, high-dose, late-intensification chemotherapy in high-risk breast cancer patients: a randomized trial. J Natl Cancer Inst. 2004 Jul 21;96(14):1076-83. link to original article contains protocol PubMed
- ECTO: Gianni L, Baselga J, Eiermann W, Porta VG, Semiglazov V, Lluch A, Zambetti M, Sabadell D, Raab G, Cussac AL, Bozhok A, Martinez-Agulló A, Greco M, Byakhov M, Lopez JJ, Mansutti M, Valagussa P, Bonadonna G. Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol. 2009 May 20;27(15):2474-81. Epub 2009 Mar 30. link to original article contains verified protocol PubMed
EC
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EC: Epirubicin and Cyclophosphamide
Variant #1, 60/500 x 8
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Piccart et al. 2001 (Belgian trial) | Phase III (E) | 1. CMF | Seems not superior |
2. High-dose EC | Seems to have inferior EFS |
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 8 cycles
Variant #2, 75/600 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pico et al. 2004 (GEICAM 9401) | Phase III (E) | ECT (Tamoxifen) | Seems not superior |
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Tamoxifen
Variant #3, 75/700 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Polyzos et al. 2009 | Phase III (E) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery, then T (Taxotere) x 4
Chemotherapy
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 700 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Variant #4, 90/600 x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ejlertsen et al. 2017 (DBCG 07-READ) | Phase III (E) | See link | See link |
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 were TOP2A normal as determined by FISH.
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Variant #5, 90/600 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Zander et al. 2004 | Non-randomized portion of RCT | ||
Colleoni et al. 2006 (IBCSG 13-93) | Non-randomized portion of RCT | ||
Kümmel et al. 2006 | Phase III (C) | See link | See link |
Martín et al. 2015 (GEICAM/2003-10) | Phase III (E) | See link | See link |
Del Mastro et al. 2015 (GIM2) | Phase III (C) | See link | See link |
Earl et al. 2017 (tAnGo) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Zander et al. 2004: CMF x 3 versus cyclophosphamide, mitoxantrone, thiotepa with auto HSCT
- IBCSG 13-93: CMF x 3, then Tamoxifen x 5 y versus no further treatment
- GEICAM/2003-10: Docetaxel
- GIM2: Paclitaxel, q3wk dosing x 4
- tAnGo: Paclitaxel, q3wk dosing x 4 versus TG x 4
Variant #6, 100/830 x 8
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Piccart et al. 2001 (Belgian trial) | Phase III (E) | 1. CMF | Seems not superior |
2. Moderate-dose EC | Seems to have superior EFS |
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 830 mg/m2 IV once on day 1
21-day cycle for 8 cycles
Variant #7, 120/600 x 4 (high-dose)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Papaldo et al. 2003 | Phase III (C) | EC & Lonidamine | Seems not superior |
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Variant #8, with range
Study | Evidence |
---|---|
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in had HER2-positive breast cancer.
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- TH (Taxol) versus THP (Taxol) or TH (Taxotere) versus THP (Taxotere)
References
- 'Belgian trial: Piccart MJ, Di Leo A, Beauduin M, Vindevoghel A, Michel J, Focan C, Tagnon A, Ries F, Gobert P, Finet C, Closon-Dejardin MT, Dufrane JP, Kerger J, Liebens F, Beauvois S, Bartholomeus S, Dolci S, Lobelle JP, Paesmans M, Nogaret JM. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001 Jun 15;19(12):3103-10. link to original article PubMed
- Update: de Azambuja E, Paesmans M, Beauduin M, Vindevoghel A, Cornez N, Finet C, Ries F, Closon-Dejardin MT, Kerger J, Gobert P, Focan C, Tagnon A, Dolci S, Nogaret JM, di Leo A, Piccart-Gebhart MJ. Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node-positive breast cancer: 15-year efficacy results of the Belgian multicentre study. J Clin Oncol. 2009 Feb 10;27(5):720-5. Epub 2008 Dec 22. link to original article PubMed
- Papaldo P, Lopez M, Cortesi E, Cammilluzzi E, Antimi M, Terzoli E, Lepidini G, Vici P, Barone C, Ferretti G, Di Cosimo S, Nistico C, Carlini P, Conti F, Di Lauro L, Botti C, Vitucci C, Fabi A, Giannarelli D, Marolla P. Addition of either lonidamine or granulocyte colony-stimulating factor does not improve survival in early breast cancer patients treated with high-dose epirubicin and cyclophosphamide. J Clin Oncol. 2003 Sep 15;21(18):3462-8. link to original article contains protocol PubMed
- GEICAM 9401: Pico C, Martin M, Jara C, Barnadas A, Pelegri A, Balil A, Camps C, Frau A, Rodriguez-Lescure A, Lopez-Vega JM, De La Haba J, Tres A, Alvarez I, Alba E, Arcusa A, Oltra A, Batista N, Checa T, Perez-Carrion R, Curto J; GEICAM Group. Epirubicin-cyclophosphamide adjuvant chemotherapy plus tamoxifen administered concurrently versus sequentially: randomized phase III trial in postmenopausal node-positive breast cancer patients: a GEICAM 9401 study. Ann Oncol. 2004 Jan;15(1):79-87. link to original article contains protocol PubMed
- Zander AR, Kröger N, Schmoor C, Krüger W, Möbus V, Frickhofen N, Metzner B, Schultze W, Berdel WE, Koenigsmann M, Thiel E, Wandt H, Possinger K, Trümper L, Kreienberg R, Carstensen M, Schmidt EH, Jänicke F, Schumacher M, Jonat W. High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: first results of a randomized trial. J Clin Oncol. 2004 Jun 15;22(12):2273-83. Epub 2004 Apr 26. link to original article contains protocol PubMed
- IBCSG 13-93: Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiglione-Gertsch M, Price KN, Coates AS, Gelber RD; International Breast Cancer Study Group. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol. 2006 Mar 20;24(9):1332-41. Epub 2006 Feb 27. link to original article contains verified protocol PubMed
- Kümmel S, Krocker J, Kohls A, Breitbach GP, Morack G, Budner M, Blohmer JU, Elling D. Randomised trial: survival benefit and safety of adjuvant dose-dense chemotherapy for node-positive breast cancer. Br J Cancer. 2006 May 8;94(9):1237-44. link to original article link to PMC article contains protocol PubMed
- Polyzos A, Malamos N, Boukovinas I, Adamou A, Ziras N, Kalbakis K, Kakolyris S, Syrigos K, Papakotoulas P, Kouroussis C, Karvounis N, Vamvakas L, Christophyllakis C, Athanasiadis A, Varthalitis I, Georgoulias V, Mavroudis D. FEC versus sequential docetaxel followed by epirubicin/cyclophosphamide as adjuvant chemotherapy in women with axillary node-positive early breast cancer: a randomized study of the Hellenic Oncology Research Group (HORG). Breast Cancer Res Treat. 2010 Jan;119(1):95-104. Epub 2009 Jul 28. link to original article contains protocol PubMed
- GOIM 9902: Vici P, Brandi M, Giotta F, Foggi P, Schittulli F, Di Lauro L, Gebbia N, Massidda B, Filippelli G, Giannarelli D, Di Benedetto A, Mottolese M, Colucci G, Lopez M. A multicenter phase III prospective randomized trial of high-dose epirubicin in combination with cyclophosphamide (EC) versus docetaxel followed by EC in node-positive breast cancer. GOIM (Gruppo Oncologico Italia Meridionale) 9902 study. Ann Oncol. 2012 May;23(5):1121-9. Epub 2011 Sep 28. link to original article link to PMC article contains protocol PubMed
- 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
- GEICAM/2003-10: Martín M, Ruiz Simón A, Ruiz Borrego M, Ribelles N, Rodríguez-Lescure A, Muñoz-Mateu M, González S, Margelí Vila M, Barnadas A, Ramos M, Del Barco Berron S, Jara C, Calvo L, Martínez-Jáñez N, Mendiola Fernández C, Rodríguez CA, Martínez de Dueñas E, Andrés R, Plazaola A, de la Haba-Rodríguez J, López-Vega JM, Adrover E, Ballesteros AI, Santaballa A, Sánchez-Rovira P, Baena-Cañada JM, Casas M, del Carmen Cámara M, Carrasco EM, Lluch A. Epirubicin plus cyclophosphamide followed by docetaxel versus epirubicin plus docetaxel followed by capecitabine as adjuvant therapy for node-positive early breast cancer: results from the GEICAM/2003-10 study. J Clin Oncol. 2015 Nov 10;33(32):3788-95. Epub 2015 Sep 28. link to original article contains verified protocol PubMed
- 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
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
- DBCG 07-READ: Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Højris I, Ewertz M, Balslev E, Danø H, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol. 2017 Aug 10;35(23):2639-2646. Epub 2017 Jun 29. link to original article contains verified protocol PubMed
EP
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EP: Epirubicin & Paclitaxel
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fountzilas et al. 2007 (HE 10/00) | Phase III (C) | ddE, then ddP | Seems not superior |
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 83 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 187 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- ddCMF x 3
References
- HE 10/00: Fountzilas G, Dafni U, Gogas H, Linardou H, Kalofonos HP, Briasoulis E, Pectasides D, Samantas E, Bafaloukos D, Stathopoulos GP, Karina M, Papadimitriou C, Skarlos D, Pisanidis N, Papakostas P, Markopoulos C, Tzorakoeleftherakis E, Dimitrakakis K, Makrantonakis P, Xiros N, Polichronis A, Varthalitis I, Karanikiotis C, Dimopoulos AM; Hellenic Cooperative Oncology Group. Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00. Ann Oncol. 2008 May;19(5):853-60. Epub 2007 Nov 27. link to original article contains verified protocol PubMed
- Update: Gogas H, Dafni U, Karina M, Papadimitriou C, Batistatou A, Bobos M, Kalofonos HP, Eleftheraki AG, Timotheadou E, Bafaloukos D, Christodoulou C, Markopoulos C, Briasoulis E, Papakostas P, Samantas E, Kosmidis P, Stathopoulos GP, Karanikiotis C, Pectasides D, Dimopoulos MA, Fountzilas G. Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial. Breast Cancer Res Treat. 2012 Apr;132(2):609-19. Epub 2011 Dec 21. link to original article PubMed
iddEPC
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iddEPC: intense dose-dense Epirubicin, Paclitaxel, Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Möbus et al. 2010 | Phase III (E) | EC, then Paclitaxel | Seems to have superior OS |
Möbus et al. 2017 (GAIN) | Phase III (C) | ddEC, then PwX | Seems not superior |
Note: this dosing of cyclophosphamide was after a mid-protocol amendment.
Preceding treatment
Chemotherapy, part 1
- Epirubicin (Ellence) 150 mg/m2 IV once on day 1
Supportive medications
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2 or 4
14-day cycle for 3 cycles, then:
Chemotherapy, part 2
- Paclitaxel (Taxol) 225 mg/m2 IV once on day 1
Supportive medications
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2 or 4
14-day cycle for 3 cycles, then:
Chemotherapy, part 3
- Cyclophosphamide (Cytoxan) 2000 mg/m2 IV once on day 1
Supportive medications
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2 or 4
14-day cycle for 3 cycles
References
- Moebus V, Jackisch C, Lueck HJ, du Bois A, Thomssen C, Kurbacher C, Kuhn W, Nitz U, Schneeweiss A, Huober J, Harbeck N, von Minckwitz G, Runnebaum IB, Hinke A, Kreienberg R, Konecny GE, Untch M. Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer: mature results of an AGO phase III study. J Clin Oncol. 2010 Jun 10;28(17):2874-80. Epub 2010 May 10. link to original article PubMed
- GAIN: Möbus V, von Minckwitz G, Jackisch C, Lück HJ, Schneeweiss A, Tesch H, Elling D, Harbeck N, Conrad B, Fehm T, Huober J, Müller V, Bauerfeind I, du Bois A, Loibl S, Nekljudova V, Untch M, Thomssen C; German Breast Group (GBG), the AGO Breast Study Group (AGO-B) and NOGGO Study Groups. German Adjuvant Intergroup Node-positive Study (GAIN): a phase III trial comparing two dose-dense regimens (iddEPC versus ddEC-PwX) in high-risk early breast cancer patients. Ann Oncol. 2017 Aug 1;28(8):1803-1810. link to original article contains verified protocol PubMed
Epirubicin monotherapy
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E: Epirubicin
Variant #1, 50 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Coombes et al. 2011 (DEVA) | Phase III (E) | See link | See link |
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
- Epirubicin (Ellence) 50 mg/m2 IV once per day on days 1 & 8
28-day cycle for 3 cycles
Subsequent treatment
- Docetaxel x 3
Variant #2, 75 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Boccardo et al. 1990 (GROCTA-1) | Phase III (E) | See link | See link |
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
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Tamoxifen x 5 y versus no further treatment
Variant #3, 90 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mavroudis et al. 2017 | Phase III (E) | See link | See link |
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
- Epirubicin (Ellence) 90 mg/m2 IV over 5 to 15 minutes once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Variant #4, 100 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Poole et al. 2006 (NEAT/BR9601) | Phase III (E) | See link | See link |
Ellis et al. 2009 (TACT) | Randomized Phase II (C) | See link | See link |
Boccardo et al. 2010 | Phase III (C) | T-EV | Seems not superior |
Amadori et al. 2010 | Phase III (E) | See note | See note |
Cameron et al. 2017 (TACT2) | Phase III (C) | See link | See link |
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. Amadori et al. 2010 was a sequencing trial comparing E -> CMF with CMF -> E; there were no statistically significant differences in outcome.
Preceding treatment
Chemotherapy
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- NEAT, TACT, BR9601, Boccardo et al. 2010: CMF
- TACT2: capecitabine versus CMF
References
- GROCTA-1: Boccardo F, Rubagotti A, Bruzzi P, Cappellini M, Isola G, Nenci I, Piffanelli A, Scanni A, Sismondi P, Santi L, Genta F, Saccani F, Sassi M, Malacarne P, Donati D, Farris A, Castagnetta L, Di Carlo A, Traina A, Galletto L, Smerieri F, Buzzi F; Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group. Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. J Clin Oncol. 1990 Aug;8(8):1310-20. link to original article contains verified protocol PubMed
- Update: Boccardo F, Guglielmini P, Parodi A, Rubagotti A. Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen receptor-positive breast cancer patients: very late results of the 'gruppo di ricerca per la chemio-ormonoterapia adiuvante (GROCTA)' 01-Trial in early breast cancer. Breast Cancer Res Treat. 2011 Apr;126(3):653-61. Epub 2011 Feb 24. link to original article PubMed
- Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. link to original article contains verified protocol PubMed
- Update: Earl HM, Hiller L, Dunn JA, Vallier AL, Bowden SJ, Jordan SD, Blows F, Munro A, Bathers S, Grieve R, Spooner DA, Agrawal R, Fernando I, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, McAdam K, Foster L, Leonard RC, Twelves CJ, Cameron D, Bartlett JM, Pharoah P, Provenzano E, Caldas C, Poole CJ; NEAT Investigators and the SCTBG. Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials. Br J Cancer. 2012 Oct 9;107(8):1257-67. Epub 2012 Sep 11. link to original article link to PMC article PubMed
- TACT: Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. link to original article link to PMC article contains verified protocol PubMed
- Boccardo F, Amadori D, Guglielmini P, Sismondi P, Farris A, Agostara B, Gambi A, Catalano G, Faedi M, Rubagotti A. Epirubicin followed by cyclophosphamide, methotrexate and 5-fluorouracil versus paclitaxel followed by epirubicin and vinorelbine in patients with high-risk operable breast cancer. Oncology. 2010;78(3-4):274-81. Epub 2010 Jun 8. link to original article contains protocol PubMed
- Amadori D, Silvestrini R, De Lena M, Boccardo F, Rocca A, Scarpi E, Schittulli F, Brandi M, Maltoni R, Serra P, Ponzone R, Biglia N, Gianni L, Tienghi A, Valerio MR, Bonginelli P, Amaducci L, Faedi M, Baldini E, Paradiso A. Randomized phase III trial of adjuvant epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) versus CMF followed by epirubicin in patients with node-negative or 1-3 node-positive rapidly proliferating breast cancer. Breast Cancer Res Treat. 2011 Feb;125(3):775-84. Epub 2010 Dec 4. link to original article contains verified protocol PubMed
- Coombes RC, Bliss JM, Espie M, Erdkamp F, Wals J, Tres A, Marty M, Coleman RE, Tubiana-Mathieu N, den Boer MO, Wardley A, Kilburn LS, Cooper D, Thomas MW, Reise JA, Wilkinson K, Hupperets P. Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with node-positive breast cancer. J Clin Oncol. 2011 Aug 20;29(24):3247-54. Epub 2011 Jul 18. link to original article contains protocol PubMed
- Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, Agrawal R, Banerji J, Bertelli G, Bloomfield D, Brunt AM, Earl H, Ellis P, Gaunt C, Gillman A, Hearfield N, Laing R, Murray N, Couper N, Stein RC, Verrill M, Wardley A, Barrett-Lee P, Bliss JM; TACT2 Investigators. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2017 Jul;18(7):929-945. Epub 2017 Jun 7. link to original article link to PMC article contains verified protocol PubMed
- Mavroudis D, Saloustros E, Boukovinas I, Papakotoulas P, Kakolyris S, Ziras N, Christophylakis C, Kentepozidis N, Fountzilas G, Rigas G, Varthalitis I, Kalbakis K, Agelaki S, Hatzidaki D, Georgoulias V. Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group. Br J Cancer. 2017 Jul 11;117(2):164-170. Epub 2017 Jun 22. link to original article contains verified protocol link to PMC article PubMed
FAC
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FAC: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide
CAF: Cyclophosphamide, Adriamycin (Doxorubicin), Fluorouracil
Variant #1, 500/50/500 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martín et al. 2013 (GEICAM/2003-02) | Phase III (E) | See link | See link |
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
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- wP x 8
Variant #2, 500/50/500 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martin et al. 2003 | Phase III (E) | CMF | Seems to have superior OS |
Martin et al. 2005 (BCIRG 001) | Phase III (C) | TAC | Inferior OS |
Martín et al. 2010 (GEICAM 9805) | Phase III (C) | TAC | Inferior DFS |
Martín et al. 2013 (GEICAM/2003-02) | Phase III (C) | FAC-wP | Seems to have inferior DFS |
Preceding treatment
Chemotherapy
Infusion times per Martin et al. 2005 (BCIRG 001).
- Fluorouracil (5-FU) 500 mg/m2 IV over 15 minutes once on day 1, given second
- Doxorubicin (Adriamycin) 50 mg/m2 IV over 15 minutes once on day 1, given first
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV over 1 to 5 minutes once on day 1, given third
- A HemOnc.org user reached out to us and said their institutional practice is to infuse cyclophosphamide over 20 to 30 minutes to decrease the likelihood of head and sinus pain.
Supportive medications
- If patients had febrile neutropenia or infection: Ciprofloxacin (Cipro) 500 mg PO BID on days 5 to 14 of every cycle
- G-CSF not originally routinely administered unless patients had febrile neutropenia:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 4 to 11
- OR Lenograstim (Granocyte) 150 mcg/m2 SC once per day on days 4 to 11
21-day cycle for 6 cycles
Variant #3, 800/40/400 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Wood et al. 1994 (CALGB 8541) | Phase III (C) | 1. FAC 600/30/300 x 4 | Superior OS |
2. FAC 1200/60/600 x 4 | Seems not superior |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 400 mg/m2 IV once on day 1
28-day cycle for 6 cycles
Variant #4, 800/40/400 until max doxorubicin
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Buzdar et al. 1984 | Phase III (C) | FAC + BCG | Seems not superior |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 400 mg/m2 IV once on day 1
21-day cycles until cumulative doxorubicin dose of 300 mg/m2 reached.
Subsequent treatment
- After reaching cumulative maximum doxorubicin, patients would go on to receive maintenance CMF. This is now obsolete.
Variant #5, 1000/50/500 x 8
Study | Evidence |
---|---|
Hortobagyi et al. 2000 | Non-randomized portion of RCT |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 4
- Doxorubicin (Adriamycin) 16.7 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 50 mg/m2)
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 8 cycles
Subsequent treatment
- CEP with auto HSCT versus no further treatment
Variant #6, 1000/60/1400 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Tallman et al. 2003 | Non-randomized portion of RCT | ||
Davidson et al. 2005 (ECOG E5188) | Non-randomized portion of RCT | ||
Hutchins et al. 2005 (INT-0102) | Phase III (E) | CMF | Seems to have superior OS |
Albain et al. 2009 (SWOG-8814) | Phase III (*) | See link | See link |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
28-day cycle for 6 cycles
Subsequent treatment
- Tallman et al. 2003: Cyclophosphamide & thiotepa with auto HSCT versus no further chemotherapy
- ECOG E5188: Goserelin x 5 y versus Goserelin & Tamoxifen x 5 y versus no further treatment
- SWOG-8814: Tamoxifen x 5 y
Variant #7, 1200/60/600 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Wood et al. 1994 (CALGB 8541) | Phase III (C) | 1. FAC 600/30/300 x 4 | Superior OS |
2. FAC 800/40/400 x 6 | Seems not superior |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
28-day cycle for 4 cycles
Variant #8, with range x 3
Study | Evidence |
---|---|
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients had HER2-positive breast cancer. Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- TH (Taxol) versus THP (Taxol) or TH (Taxotere) versus THP (Taxotere)
References
- Buzdar AU, Blumenschein GR, Smith TL, Powell KC, Hortobagyi GN, Yap HY, Schell FC, Barnes BC, Ames FC, Martin RG, Hersh EM. Adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide, with or without Bacillus Calmette-Guérin and with or without irradiation in operable breast cancer: a prospective randomized trial. Cancer. 1984 Feb 1;53(3):384-9. link to original article contains verified protocol PubMed
- Update: Buzdar AU, Kau SW, Smith TL, Hortobagyi GN. Ten-year results of FAC adjuvant chemotherapy trial in breast cancer. Am J Clin Oncol. 1989 Apr;12(2):123-8. PubMed
- CALGB 8541: Wood WC, Budman DR, Korzun AH, Cooper MR, Younger J, Hart RD, Moore A, Ellerton JA, Norton L, Ferree CR, Ballow AC, Frei E, Henderson IC. Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med. 1994 May 5;330(18):1253-9. Erratum in: N Engl J Med 1994 Jul 14;331(2):139. link to original article contains verified protocol PubMed
- Subgroup analysis: Muss HB, Thor AD, Berry DA, Kute T, Liu ET, Koerner F, Cirrincione CT, Budman DR, Wood WC, Barcos M, Henderson IC. c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med. 1994 May 5;330(18):1260-6. Erratum in: N Engl J Med 1994 Jul 21;331(3):211. link to original article PubMed
- Hortobagyi GN, Buzdar AU, Theriault RL, Valero V, Frye D, Booser DJ, Holmes FA, Giralt S, Khouri I, Andersson B, Gajewski JL, Rondon G, Smith TL, Singletary SE, Ames FC, Sneige N, Strom EA, McNeese MD, Deisseroth AB, Champlin RE. Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma. J Natl Cancer Inst. 2000 Feb 2;92(3):225-33. link to original article contains verified protocol PubMed
- Martin M, Villar A, Sole-Calvo A, Gonzalez R, Massuti B, Lizon J, Camps C, Carrato A, Casado A, Candel MT, Albanell J, Aranda J, Munarriz B, Campbell J, Diaz-Rubio E; GEICAM Group (Spanish Breast Cancer Research Group), Spain. Doxorubicin in combination with fluorouracil and cyclophosphamide (iv FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (iv CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group. Ann Oncol. 2003 Jun;14(6):833-42. link to original article contains protocol PubMed
- 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
- Tallman MS, Gray R, Robert NJ, LeMaistre CF, Osborne CK, Vaughan WP, Gradishar WJ, Pisansky TM, Fetting J, Paietta E, Lazarus HM. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. N Engl J Med. 2003 Jul 3;349(1):17-26. link to original article PubMed
- BCIRG 001: Martín M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, Guevin R, Howell A, Fornander T, Hainsworth J, Coleman R, Vinholes J, Modiano M, Pinter T, Tang SC, Colwell B, Prady C, Provencher L, Walde D, Rodriguez-Lescure A, Hugh J, Loret C, Rupin M, Blitz S, Jacobs P, Murawsky M, Riva A, Vogel C; Breast Cancer International Research Group 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13. link to original article contains protocol PubMed
- Update: Mackey JR, Martín M, Pienkowski T, Rolski J, Guastalla JP, Sami A, Glaspy J, Juhos E, Wardley A, Fornander T, Hainsworth J, Coleman R, Modiano MR, Vinholes J, Pinter T, Rodríguez-Lescure A, Colwell B, Whitlock P, Provencher L, Laing K, Walde D, Price C, Hugh JC, Childs BH, Bassi K, Lindsay MA, Wilson V, Rupin M, Houé V, Vogel C; TRIO/BCIRG 001 investigators. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol. 2013 Jan;14(1):72-80. Epub 2012 Dec 12. link to original article PubMed
- ECOG E5188: Davidson NE, O'Neill AM, Vukov AM, Osborne CK, Martino S, White DR, Abeloff MD. Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188). J Clin Oncol. 2005 Sep 1;23(25):5973-82. Epub 2005 Aug 8. link to original article contains verified protocol PubMed
- INT-0102: Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. 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 Nov 20;23(33):8313-21. link to original article PubMed
- SWOG-8814: Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, Cobau CD, Levine EG, Ingle JN, Pritchard KI, Lichter AS, Schneider DJ, Abeloff MD, Henderson IC, Muss HB, Green SJ, Lew D, Livingston RB, Martino S, Osborne CK; Breast Cancer Intergroup of North America. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Dec 19;374(9707):2055-2063. Epub 2009 Dec 10. link to original article link to PMC article contains verified protocol PubMed
- GEICAM 9805: Martín M, Seguí MA, Antón A, Ruiz A, Ramos M, Adrover E, Aranda I, Rodríguez-Lescure A, Grosse R, Calvo L, Barnadas A, Isla D, Martinez del Prado P, Ruiz Borrego M, Zaluski J, Arcusa A, Muñoz M, López Vega JM, Mel JR, Munarriz B, Llorca C, Jara C, Alba E, Florián J, Li J, López García-Asenjo JA, Sáez A, Rios MJ, Almenar S, Peiró G, Lluch A; GEICAM 9805 Investigators. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med. 2010 Dec 2;363(23):2200-10. link to original article PubMed
- GEICAM/2003-02: Martín M, Ruiz A, Ruiz Borrego M, Barnadas A, González S, Calvo L, Margelí Vila M, Antón A, Rodríguez-Lescure A, Seguí-Palmer MA, Muñoz-Mateu M, Dorca Ribugent J, López-Vega JM, Jara C, Espinosa E, Mendiola Fernández C, Andrés R, Ribelles N, Plazaola A, Sánchez-Rovira P, Salvador Bofill J, Crespo C, Carabantes FJ, Servitja S, Chacón JI, Rodríguez CA, Hernando B, Álvarez I, Carrasco E, Lluch A. Fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus FAC followed by weekly paclitaxel as adjuvant therapy for high-risk, node-negative breast cancer: results from the GEICAM/2003-02 study. J Clin Oncol. 2013 Jul 10;31(20):2593-9. Epub 2013 Jun 3. link to original article contains verified protocol PubMed
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
FEC
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FEC: Fluorouracil, Epirubicin, Cyclophosphamide
CEF: Cyclophosphamide, Epirubicin, Fluorouracil
Variant #1, 500/50/500 x 6 ("FEC50")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hurteloup 1988 (FESG) | Phase III (E) | FAC | Seems not superior |
Bonneterre 2001 (FASG 05) | Phase III (C) | FEC100 x 6 | Inferior OS |
Fumoleau et al. 2003 (FASG 01) | Phase III (E) | 1. FEC 50 x 3 | Might have superior OS |
2. FEC 75 x 3 | Seems not superior | ||
Arriagada et al. 2005 | Phase III (E) | Observation | Superior DFS |
Héry et al. 2006 (FASG 03) | Phase III (E) | Observation | Seems not superior |
Roché et al. 2006 (FASG 06) | Phase III (C) | Goserelin & Tamoxifen x 3y | Seems not superior |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Variant #2, 500/60/500 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Rouëssé et al. 2006 | Phase III (C) | FNC & RT | Seems not superior |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Variant #3, 500/100/500 x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Roché et al. 2006 (FNCLCC PACS 01) | Phase III (E) | See link | See link |
Baselga et al. 2012 (NeoALTTO) | Non-randomized portion of RCT | ||
Foukakis et al. 2016 (PANTHER) | Phase III (C) | Dose-dense tailored chemotherapy | 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 NeoALTTO all had HER2-positive disease.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- FNCLCC PACS 01 & PANTHER: Docetaxel x 3
- NeoALTTO: Lapatinib or Lapatinib & Trastuzumab or Trastuzumab, according to initial randomization
Variant #4, 500/100/500 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kelly et al. 2012 | Non-randomized portion of RCT | ||
Kerbrat et al. 2017 (UCBG-0106) | Phase III (E) | FEC100 x 6 | Seems not superior |
Note: this is an experimental arm that did not meet its primary endpoint; included here because it represents a de-escalation strategy.
Preceding treatment
- Kelly et al. 2012: Surgery, then weekly paclitaxel x 12 versus XT
- UCBG-0106: Surgery
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Variant #5, 500/100/500 x 6 ("FEC100")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bonneterre 2001 (FASG 05) | Phase III (E) | FEC50 x 6 | Superior OS |
Roché et al. 2006 (FNCLCC PACS 01) | Phase III (C) | FEC-D | Inferior OS (*) |
Kerbrat et al. 2007 (FASG 09) | Phase III (C) | Epirubicin & Vinorelbine | Seems not superior |
Sakr et al. 2013 | Phase III (C) | FEC100 x 3, then D x 3 | Seems to have inferior OS |
Delbaldo et al. 2013 (Trial B2000) | Phase III (C) | FEC100 x 4, then Taxol x 4 | Seems not superior |
Nitz et al. 2014 (WSG-AGO EC-Doc) | Phase III (C) | EC-Doc | Seems to have inferior OS |
Kerbrat et al. 2017 (UCBG-0106) | Phase III (C) | FEC100 x 4 | Seems not superior |
Note: efficacy for FNCLCC PACS 01 is based on the 2012 update.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Variant #6, 600/50/600 x 8
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Coombes et al. 1996 | Phase III (E) | CMF | Seems not superior |
Coombes et al. 2016 (HMFEC) | Phase III (C) | FEC75 | Seems not superior |
Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 8 cycles
Variant #7, 600/60/600 x 3
Study | Evidence |
---|---|
Joensuu et al. 2006 (FinHer) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- HER2-negative: Docetaxel x 3 versus Vinorelbine x 3
- HER2-positive: Docetaxel x 3 versus TH x 3 versus Vinorelbine x 3 versus VH x 3
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Variant #8, 600/60/600 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
van der Hage et al. 2001 (EORTC 10902) | Phase III (C) | Neoadjuvant FEC | Seems not superior |
Ellis et al. 2009 (TACT) | Randomized Phase II (E) | See link | See link |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- TACT: D x 4
Variant #9, 600/60/600 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Venturini et al. 2005 | Phase III (C) | ddFEC | Seems not superior |
Sirohi et al. 2010 (TRAFIC) | Phase III (C) | ECisF | Seems not superior |
del Mastro et al. 2016 (GONO-MIG5) | Phase III (C) | EP x 4 | Seems not superior |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Variant #10, 600/60/600 x 8
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ellis et al. 2009 (TACT) | Randomized Phase II (C) | See link | See link |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 8 cycles
Variant #11, 600/60/600 x 9
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ejlertsen et al. 2007 | Phase III (E) | CMF | Superior OS |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 9 cycles
Variant #12, 600/75/600 x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Joensuu et al. 2009 (FinXX) | Phase III (C) | See link | See link |
Joensuu et al. 2018 (SOLD) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in SOLD had HER2+ breast cancer.
Preceding treatment
- FinXX: Surgery, then T (Taxotere) x 3
- SOLD: Surgery, then TH (Taxotere) x 3
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- SOLD: Trastuzumab maintenance for a total of 1 year versus no further treatment
Variant #13, 600/90/600 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martín et al. 2008 (GEICAM 9906) | Phase III (E) | See link | See link |
Del Mastro et al. 2015 (GIM2) | Phase III (E) | See link | See link |
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
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- GEICAM 9906: Weekly Paclitaxel
- GIM2: Paclitaxel, q3wk dosing
Variant #14, 600/90/600 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martín et al. 2008 (GEICAM 9906) | Phase III (C) | FEC x 4, then wP | Inferior DFS |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Variant #15, 700/75/700 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Polyzos et al. 2009 | Phase III (C) | D, then EC | Seems to have inferior DFS |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 700 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 700 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Variant #16, 1000/50/500 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Paradiso et al. 2001 | Phase III (E) | Observation | Seems to have superior DFS |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Variant #17, 1000/50/500 until max anthracycline
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Ambrosini et al. 1988 | Phase III (E) | FAC | Seems not superior | Less toxic |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for up to 14 cycles (maximum of 700 mg/m2 epirubicin)
Variant #18, 1000/120/1050 x 6 ("FEC120")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Levine et al. 1998 (NCIC CTG MA.5) | Phase III (E) | CMF | Superior RFS |
Coombes et al. 2005 (ICCG HDT trial) | Phase III (C) | FEC x 3, then HDT | Seems not superior |
Burnell et al. 2009 (NCIC CTG MA.21) | Phase III (C) | 1. AC x 4, then T (Taxol) x 4 | Superior RFS |
2. ddEC x 6, then T (Taxol) x 4 | Seems not superior | ||
Janni et al. 2016 (ADEBAR) | Phase III (C) | EC x 3, then Docetaxel | Seems not superior |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Epirubicin (Ellence) 60 mg/m2 IV once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 75 mg/m2 PO once per day on days 1 to 14
28-day cycle for 6 cycles
Variant #19, 1200/50/1200 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Coombes et al. 1996 | Phase III (E) | CMF | Seems not superior |
Note: this is an experimental arm that did not meet its primary endpoint; however, based on a subgroup analysis, it became a preferred regimen.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
Variant #20, with range x 3
Study | Evidence |
---|---|
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients had HER2-positive breast cancer. Note that ranges for FEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- TH (Taxol) versus THP (Taxol) or TH (Taxotere) versus THP (Taxotere)
References
- FESG: Hurteloup P; French Epirubicin Study Group. A prospective randomized phase III trial comparing combination chemotherapy with cyclophosphamide, fluorouracil, and either doxorubicin or epirubicin. J Clin Oncol. 1988 Apr;6(4):679-88. link to original article contains protocol PubMed
- Ambrosini G, Balli M, Garusi G, Demicheli R, Jirillo A, Bonciarelli G, Bruscagnin G, Fila G, Bumma C, Lacroix F, Buzzi F, Di Costanzo F, Padalino D, Brugia M, Calabresi F, Natali M, Cartei G, Chiesa G, Blasina B, Ciambellotti E, Moro G, D'Aquino S, Altavilla G, Adamo V, De Maria D, Falchi AM, Bertoncelli P, Farris A, Fiorentino M, Fornasiero A, Fosser V, Daniele O, Foggi CM, Speranza GB, Sartori S, Camilluzzi E, Gallo L, Poggio R, Secondo V, Gambi A, Grignani F, Capodicasa E, Lopez M, Papaldo P, Di Lauro L, Vici P, Marenco G, Folco U, Bonanni F, Marsilio P, Palazzotto G, Di Carlo A, Cusimano MP, Pastorino G, Puccetti C, Giusto M, Rausa L, Gebbia N, Palmeri S, D'Alessandro N, Saccani F, Becchi G, Schieppati G, Spinelli I, Tagliagambe A, Tonato M, Minotti V, Ardia A, Viaro D, De Micheli P, Zingali G, Sacchetti G, Intini C; Italian Multicentre Breast Study with Epirubicin. Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial. J Clin Oncol. 1988 Jun;6(6):976-82. link to original article contains protocol PubMed
- Coombes RC, Bliss JM, Wils J, Morvan F, Espié M, Amadori D, Gambrosier P, Richards M, Aapro M, Villar-Grimalt A, McArdle C, Pérez-López FR, Vassilopoulos P, Ferreira EP, Chilvers CE, Coombes G, Woods EM, Marty M; The International Collaborative Cancer Group. Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. J Clin Oncol. 1996 Jan;14(1):35-45. link to original article contains verified protocol PubMed
- NCIC CTG MA.5: Levine MN, Bramwell VH, Pritchard KI, Norris BD, Shepherd LE, Abu-Zahra H, Findlay B, Warr D, Bowman D, Myles J, Arnold A, Vandenberg T, MacKenzie R, Robert J, Ottaway J, Burnell M, Williams CK, Tu D; National Cancer Institute of Canada Clinical Trials Group. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. J Clin Oncol. 1998 Aug;16(8):2651-8. link to original article PubMed
- Update: Levine MN, Pritchard KI, Bramwell VH, Shepherd LE, Tu D, Paul N; National Cancer Institute of Canada Clinical Trials Group. 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 Aug 1;23(22):5166-70. link to original article PubMed
- Subgroup analysis: Pritchard KI, Shepherd LE, O'Malley FP, Andrulis IL, Tu D, Bramwell VH, Levine MN; National Cancer Institute of Canada Clinical Trials Group. HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med. 2006 May 18;354(20):2103-11. link to original article PubMed
- FASG 05: Bonneterre J; French Adjuvant Study Group. Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French Adjuvant Study Group 05 randomized trial. J Clin Oncol. 2001 Feb 1;19(3):602-11. link to original article contains protocol PubMed
- Update: Bonneterre J, Roché H, Kerbrat P, Brémond A, Fumoleau P, Namer M, Goudier MJ, Schraub S, Fargeot P, Chapelle-Marcillac I. Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French Adjuvant Study Group 05 randomized trial. J Clin Oncol. 2005 Apr 20;23(12):2686-93. link to original article PubMed
- Paradiso A, Schittulli F, Cellamare G, Mangia A, Marzullo F, Lorusso V, De Lena M. Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer. J Clin Oncol. 2001 Oct 1;19(19):3929-37. link to original article contains verified protocol PubMed
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- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article contains verified protocol PubMed
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU. Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol. 2012 Mar 20;30(9):930-5. Epub 2012 Feb 13. link to original article contains verified protocol PubMed
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- Trial B2000: Delbaldo C, Serin D, Mousseau M, Greget S, Audhuy B, Priou F, Berdah JF, Teissier E, Laplaige P, Zelek L, Quinaux E, Buyse M, Piedbois P; Association Européenne de Recherche en Oncologie (AERO). A phase III adjuvant randomised trial of 6 cycles of 5-fluorouracil-epirubicine-cyclophosphamide (FEC100) versus 4 FEC 100 followed by 4 Taxol (FEC-T) in node positive breast cancer patients (Trial B2000). Eur J Cancer. 2014 Jan;50(1):23-30. Epub 2013 Oct 29. link to original article PubMed
- WSG-AGO EC-Doc: Nitz U, Gluz O, Huober J, Kreipe HH, Kates RE, Hartmann A, Erber R, Moustafa Z, Scholz M, Lisboa B, Mohrmann S, Möbus V, Augustin D, Hoffmann G, Weiss E, Böhmer S, Kreienberg R, Du Bois A, Sattler D, Thomssen C, Kiechle M, Jänicke F, Wallwiener D, Harbeck N, Kuhn W. Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression. Ann Oncol. 2014 Aug;25(8):1551-7. Epub 2014 May 14. Erratum in: Ann Oncol. 2017 Nov 1;28(11):2899. link to original article contains protocol PubMed
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- GONO-MIG5: Del Mastro L, Levaggi A, Michelotti A, Cavazzini G, Adami F, Scotto T, Piras M, Danese S, Garrone O, Durando A, Accortanzo V, Bighin C, Miglietta L, Pastorino S, Pronzato P, Castiglione F, Landucci E, Conte P, Bruzzi P. 5-Fluorouracil, epirubicin and cyclophosphamide versus epirubicin and paclitaxel in node-positive early breast cancer: a phase-III randomized GONO-MIG5 trial. Breast Cancer Res Treat. 2016 Jan;155(1):117-26. link to original article contains verified protocol PubMed
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Paclitaxel monotherapy, weekly
back to top |
T: Taxol (Paclitaxel)
P: Paclitaxel
pT: pacliTaxel
wP: weekly Paclitaxel
wT: weekly Taxol (Paclitaxel)
Variant #1, 80 mg/m2 x 12
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Romond et al. 2005 (NSABP B-31) | Phase III (C) | TH | Inferior OS | Might have inferior DASI score |
Romond et al. 2005 (NCCTG N9831) | Phase III (C) | See link | See link | |
Sparano et al. 2008 (ECOG E1199) | Phase III (E) | 1. Paclitaxel q3wk | Superior OS | |
2. Docetaxel q3wk 3. Docetaxel weekly |
Not reported | |||
Kelly et al. 2012 | Phase III (C) | XT | Seems not superior | |
Shulman et al. 2012 (CALGB 40101) | Phase III (E) | 1. AC x 4 | Seems not superior | |
2. AC x 6 | Seems not superior | |||
3. Weekly paclitaxel x 18 | Seems not superior | |||
Budd et al. 2014 (SWOG S0221) | Phase III (C) | ddT x 6 | Seems not superior | |
Miller et al. 2018 (ECOG E5103) | Phase III (C) | See link | See link |
Note: Patients in NSABP B-31 and NCCTG N9831 were HER2-positive. This paclitaxel dosing schedule was an option after 2003 in NSABP B-31, and was used for all patients in NCCTG N9831. In CALGB 40101, this is the dosing before a mid-protocol amendment in 2003. 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
- NSABP B-31, NCCTG N9831, ECOG E1199: Surgery, then AC x 4
- Kelly et al. 2012: Surgery
- SWOG S0221: Surgery, then ddAC x 6 versus continuous AC
- ECOG E5103: Surgery, then AC x 4 or ddAC x 4
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per week
12-week course
Subsequent treatment
Variant #2, 100 mg/m2 x 8
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martín et al. 2008 (GEICAM 9906) | Phase III (E) | See link | See link |
Martín et al. 2013 (GEICAM/2003-02) | Phase III (E) | See link | See link |
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
- Paclitaxel (Taxol) 100 mg/m2 IV once per week
8 week course
References
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- Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU. Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol. 2012 Mar 20;30(9):930-5. Epub 2012 Feb 13. link to original article contains verified protocol PubMed
- CALGB 40101: Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article contains verified protocol link to study protocol PDF link to PMC article PubMed
- Update: Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. link to PMC article PubMed
- GEICAM/2003-02: Martín M, Ruiz A, Ruiz Borrego M, Barnadas A, González S, Calvo L, Margelí Vila M, Antón A, Rodríguez-Lescure A, Seguí-Palmer MA, Muñoz-Mateu M, Dorca Ribugent J, López-Vega JM, Jara C, Espinosa E, Mendiola Fernández C, Andrés R, Ribelles N, Plazaola A, Sánchez-Rovira P, Salvador Bofill J, Crespo C, Carabantes FJ, Servitja S, Chacón JI, Rodríguez CA, Hernando B, Álvarez I, Carrasco E, Lluch A. Fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus FAC followed by weekly paclitaxel as adjuvant therapy for high-risk, node-negative breast cancer: results from the GEICAM/2003-02 study. J Clin Oncol. 2013 Jul 10;31(20):2593-9. Epub 2013 Jun 3. link to original article contains verified protocol PubMed
- SWOG S0221: Budd GT, Barlow WE, Moore HC, Hobday TJ, Stewart JA, Isaacs C, Salim M, Cho JK, Rinn KJ, Albain KS, Chew HK, Burton GV, Moore TD, Srkalovic G, McGregor BA, Flaherty LE, Livingston RB, Lew DL, Gralow JR, Hortobagyi GN. SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. J Clin Oncol. 2015 Jan 1;33(1):58-64. Epub 2014 Nov 24. link to original article contains verified protocol link to PMC article PubMed
- ECOG E5103: Miller KD, O'Neill A, Gradishar W, Hobday TJ, Goldstein LJ, Mayer IA, Bloom S, Brufsky AM, Tevaarwerk AJ, Sparano JA, Le-Lindqwister NA, Hendricks CB, Northfelt DW, Dang CT, Sledge GW Jr. Double-blind phase III trial of adjuvant chemotherapy with and without bevacizumab in patients with lymph node-positive and high-risk lymph node-negative breast cancer (E5103). J Clin Oncol. 2018 Sep 1;36(25):2621-2629. Epub 2018 Jul 24. link to original article refers to ECOG E1199 protocol PubMed
Paclitaxel monotherapy, dose-dense (q2wk)
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ddT: dose-dense Taxol (Paclitaxel)
ddP: dose-dense Paclitaxel
Variant #1, 175 mg/m2 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Citron et al. 2003 (CALGB 9741) | Phase III (E) | See link | See link |
Burstein et al. 2005 | Non-randomized | ||
Shulman et al. 2012 (CALGB 40101) | Phase III (E) | 1. ddAC x 4 | Seems not superior |
2. ddAC x 6 | Seems not superior | ||
3. ddT x 6 | Seems not superior | ||
Swain et al. 2013 (NSABP B-38) | Phase III (C) | See link | See link |
Del Mastro et al. 2015 (GIM2) | Phase III (E) | See link | See link |
Note: in CALGB 40101, this is the dosing after a mid-protocol amendment in 2003.
Preceding treatment
- CALGB 9741: ddA x 4 or ddAC x 4
- Burstein et al. 2005: Neoadjuvant ddAC, then surgery or surgery, then adjuvant ddAC
- CALGB 40101: Surgery, within 90 days
- NSABP B-38: ddAC x 4
- GIM2: ddEC x 4 versus ddFEC x 4
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive medications
- Diphenhydramine (Benadryl) 12.5 to 50 mg IV 30 to 60 minutes prior to paclitaxel
- One of the following H2 blockers:
- Ranitidine (Zantac) 50 mg IV 30 to 60 minutes prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV 30 to 60 minutes prior to paclitaxel
- Famotidine (Pepcid) 20 mg IV 30 to 60 minutes prior to paclitaxel
- One of the following dexamethasone choices:
- Dexamethasone (Decadron) 10 mg IV less than 60 minutes prior to paclitaxel
- Dexamethasone (Decadron) 10 mg PO greater than 60 minutes prior to paclitaxel
- Dexamethasone (Decadron) 20 mg PO 6 hours and 12 hour prior to paclitaxel
- Recommended growth factor support with one of the following:
- Filgrastim (Neupogen) 5 mcg/kg (rounded to 300 mcg or 480 mcg, whichever is closer) SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Sargramostim (Leukine) 250 to 500 mcg/m2 SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Pegfilgrastim (Neulasta) 6 mg SC, administered once 24 to 36 hours after chemotherapy
- GIM2: a mid-protocol amendment suggested giving the pegilgrastim at least 72 h after chemotherapy
14-day cycle for 4 cycles
Subsequent treatment
- CALGB 9741: ddC x 4 (if preceded by ddA)
Variant #2, 175 mg/m2 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Budd et al. 2014 (SWOG S0221) | Phase III (E) | Weekly paclitaxel | 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.
Preceding treatment
- ddAC x 6 versus continuous AC
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive medications
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2
14-day cycle for 6 cycles
Variant #3, 200 mg/m2 x 4
Study | Evidence |
---|---|
Kahan et al. 2005 | Phase II |
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
- ddA x 4
Chemotherapy
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours day 1
Supportive medications
14-day cycle for 4 cycles
Subsequent treatment
References
- 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
- Kahan Z, Uhercsak G, Hajnal-Papp R, Boda K, Thurzo L. Dose-dense sequential adriamycin-paclitaxel-cyclophosphamide chemotherapy is well tolerated and safe in high-risk early breast cancer. Oncology. 2005;68(4-6):446-53. Epub 2005 Jul 13. link to original article PubMed
- Update: Kelemen G, Uhercsák G, Ormándi K, Eller J, Thurzó L, Kahán Z. Long-term efficiency and toxicity of adjuvant dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy in high-risk breast cancer. Oncology. 2010;78(3-4):271-3. Epub 2010 Jun 7. link to original article PubMed
- Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. link to original article contains verified protocol PubMed
- CALGB 40101: Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article contains verified protocol link to study protocol PDF link to PMC article PubMed
- Update: Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. link to PMC article PubMed
- NSABP B-38: Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. Epub 2013 Aug 12. link to original article link to PMC article contains verified protocol PubMed
- SWOG S0221: Budd GT, Barlow WE, Moore HC, Hobday TJ, Stewart JA, Isaacs C, Salim M, Cho JK, Rinn KJ, Albain KS, Chew HK, Burton GV, Moore TD, Srkalovic G, McGregor BA, Flaherty LE, Livingston RB, Lew DL, Gralow JR, Hortobagyi GN. SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. J Clin Oncol. 2015 Jan 1;33(1):58-64. Epub 2014 Nov 24. link to original article contains verified protocol link to PMC article PubMed
- 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
TAC (Taxotere)
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TAC: Taxotere (Docetaxel), Adriamycin (Doxorubicin), Cyclophosphamide
ACT: Adriamycin (Doxorubicin), Cyclophosphamide, Taxotere (Docetaxel)
Variant #1, 4 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Swain et al. 2010 (NSABP B-30) | Phase III (C) | See link | See link |
Note: this was a mid-protocol dosing amendment.
Preceding treatment
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV over 15 minutes once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV over 1 to 5 minutes once on day 1
21-day cycle for 4 cycles
Variant #2, 6 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martin et al. 2005 (BCIRG 001) | Phase III (E) | FAC | Superior OS |
Martín et al. 2010 (GEICAM 9805) | Phase III (E) | FAC | Superior DFS |
Eiermann et al. 2011 (BCIRG-005) | Phase III (C) | AC, then T | Seems not superior |
Swain et al. 2013 (NSABP B-38) | Phase III (C) | 1. ddAC, then ddP | Seems not superior |
2. ddAC, then ddPG | Seems not superior | ||
Blum et al. 2017 (USOR 06-090; NSABP-46-I/USOR 07132; NSABP B-49) | Phase III (C) | TC | Seems to have superior IDFS |
Note: Blum et al. 2017 is a pooled analysis of three RCTs, some of which had arms other than TAC and TC. Refer to the paper for further details.
Preceding treatment
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1, given third, one hour after cyclophosphamide
- Doxorubicin (Adriamycin) 50 mg/m2 IV over 15 minutes once on day 1, given first
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV over 1 to 5 minutes once on day 1, given second
Supportive medications
- Dexamethasone (Decadron) 8 mg PO every 12 hours x 6 total doses, starting the day before treatment
- Ciprofloxacin (Cipro) 500 mg PO BID on days 5 to 14 of every cycle (prophylaxis)
- G-CSF not originally routinely administered unless patients had febrile neutropenia, but some guidelines recommend one of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 4 to 11
- Lenograstim (Granocyte) 150 mcg/m2 SC once per day on days 4 to 11
21-day cycle for 6 cycles
References
- BCIRG 001: Martín M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, Guevin R, Howell A, Fornander T, Hainsworth J, Coleman R, Vinholes J, Modiano M, Pinter T, Tang SC, Colwell B, Prady C, Provencher L, Walde D, Rodriguez-Lescure A, Hugh J, Loret C, Rupin M, Blitz S, Jacobs P, Murawsky M, Riva A, Vogel C; Breast Cancer International Research Group 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13. link to original article contains protocol PubMed
- Update: Mackey JR, Martín M, Pienkowski T, Rolski J, Guastalla JP, Sami A, Glaspy J, Juhos E, Wardley A, Fornander T, Hainsworth J, Coleman R, Modiano MR, Vinholes J, Pinter T, Rodríguez-Lescure A, Colwell B, Whitlock P, Provencher L, Laing K, Walde D, Price C, Hugh JC, Childs BH, Bassi K, Lindsay MA, Wilson V, Rupin M, Houé V, Vogel C; TRIO/BCIRG 001 investigators. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol. 2013 Jan;14(1):72-80. Epub 2012 Dec 12. link to original article PubMed
- NSABP B-30: Swain SM, Jeong JH, Geyer CE Jr, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff J, Vogel VG, Erban JK, Rastogi P, Livingston RB, Perez EA, Mamounas EP, Land SR, Ganz PA, Wolmark N. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med. 2010 Jun 3;362(22):2053-65. link to original article link to PMC article contains verified protocol PubMed
- GEICAM 9805: Martín M, Seguí MA, Antón A, Ruiz A, Ramos M, Adrover E, Aranda I, Rodríguez-Lescure A, Grosse R, Calvo L, Barnadas A, Isla D, Martinez del Prado P, Ruiz Borrego M, Zaluski J, Arcusa A, Muñoz M, López Vega JM, Mel JR, Munarriz B, Llorca C, Jara C, Alba E, Florián J, Li J, López García-Asenjo JA, Sáez A, Rios MJ, Almenar S, Peiró G, Lluch A; GEICAM 9805 Investigators. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med. 2010 Dec 2;363(23):2200-10. link to original article PubMed
- BCIRG-005: Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martín M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press M, Sauter G, Lindsay MA, Riva A, Buyse M, Drevot P, Taupin H, Mackey JR. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011 Oct 10;29(29):3877-84. Epub 2011 Sep 12. link to original article contains verified protocol PubMed
- Update: Mackey JR, Pieńkowski T, Crown J, Sadeghi S, Martín M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press MF, Sauter G, Lindsay M, Houé V, Buyse M, Drevot P, Hitier S, Bensfia S, Eiermann W; Translational Research In Oncology (TRIO)/ Breast Cancer International Research Group (BCIRG)-005 investigators. Long-term outcomes after adjuvant treatment of sequential versus combination docetaxel with doxorubicin and cyclophosphamide in node-positive breast cancer: BCIRG-005 randomized trial. Ann Oncol. 2016 Jun;27(6):1041-7. Epub 2016 Mar 2. link to original article PubMed
- NSABP B-38: Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. Epub 2013 Aug 12. link to original article link to PMC article contains verified protocol PubMed
- USOR 06-090; NSABP-46-I/USOR 07132; NSABP B-49: Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, Robert NJ, Hopkins JO, O'Shaughnessy JA, Dang CT, Gómez HL, Fehrenbacher L, Vukelja SJ, Lyss AP, Paul D, Brufsky AM, Jeong JH, Colangelo LH, Swain SM, Mamounas EP, Jones SE, Wolmark N. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-2655. Epub 2017 Apr 11. link to original article link to PMC article contains verified protocol PubMed
Vinorelbine monotherapy
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V: Vinorelbine
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Joensuu et al. 2006 (FinHer) | Phase III (E) | 1. Docetaxel | Inferior DDFS |
2. TH (Taxotere) 3. VH |
Seems not superior |
Patients without HER2/neu amplification were only randomized to this arm verus the docetaxel arm.
Preceding treatment
Chemotherapy
- Vinorelbine (Navelbine) as follows:
- Cycles 1 & 2: 25 mg/m2 IV over 5 to 10 minutes once per day on days 1, 8, 15
- Cycle 3: 25 mg/m2 IV over 5 to 10 minutes once per day on days 1 & 8
21-day cycle for 3 cycles
Subsequent treatment
References
- FinHer: Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. link to original article contains verified protocol PubMed
- Update: Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. link to original article PubMed
Metastatic disease, first-line chemotherapy
Note: in many of these regimens, patients were allowed to have received (neo)adjuvant chemotherapy and hormonal therapy (when applicable). These are first-line regimens in the metastatic setting, with a few being specifically for the locally advanced but unresectable setting.
AC
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AC: Adriamycin (Doxorubicin) & Cyclophosphamide
Variant #1, 40/500
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Katsumata et al. 2009 (JCOG9802) | Phase III (C) | 1. AC-D | Seems not superior |
2. Docetaxel | Might have inferior OS |
Chemotherapy
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Variant #2, 40/800 (PO)
Study | Evidence |
---|---|
Jones et al. 1975 | Non-randomized |
Chemotherapy
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 200 mg/m2/day PO in divided doses on days 3 to 6
21- to 28-day cycles
Variant #3, 60/600
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Slamon et al. 2001 | Phase III (C) | ACH | Seems to have inferior OS |
Biganzoli et al. 2002 (EORTC 10961) | Phase III (C) | AT (Taxol) | Seems not superior |
Nabholtz et al. 2003 (TAX 306) | Phase III (C) | AT (Taxotere) | Seems to have inferior TTP |
Note: patients in Slamon et al. 2001 had not previously received adjuvant (postoperative) therapy with an anthracycline.
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycles (see note)
Variant #4, with range
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III (C) | AC & Bevacizumab | Inferior PFS |
Chemotherapy
- Doxorubicin (Adriamycin) 50 to 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for up to 8 cycles
References
- Jones SE, Durie BG, Salmon SE. Combination chemotherapy with adriamycin and cyclophosphamide for advanced breast cancer. Cancer. 1975 Jul;36(1):90-7. link to original article contains protocol PubMed
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. link to original article PubMed
- EORTC 10961: Biganzoli L, Cufer T, Bruning P, Coleman R, Duchateau L, Calvert AH, Gamucci T, Twelves C, Fargeot P, Epelbaum R, Lohrisch C, Piccart MJ. Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: The European Organization for Research and Treatment of Cancer 10961 multicenter phase III trial. J Clin Oncol. 2002 Jul 15;20(14):3114-21. link to original article contains protocol PubMed
- TAX 306: Nabholtz JM, Falkson C, Campos D, Szanto J, Martín M, Chan S, Pienkowski T, Zaluski J, Pinter T, Krzakowski M, Vorobiof D, Leonard R, Kennedy I, Azli N, Murawsky M, Riva A, Pouillart P; TAX 306 Study Group. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol. 2003 Mar 15;21(6):968-75. link to original article PubMed
- JCOG9802: Katsumata N, Watanabe T, Minami H, Aogi K, Tabei T, Sano M, Masuda N, Andoh J, Ikeda T, Shibata T, Takashima S. Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel, and alternating AC and docetaxel as front-line chemotherapy for metastatic breast cancer: Japan Clinical Oncology Group trial (JCOG9802). Ann Oncol. 2009 Jul;20(7):1210-5. Epub 2009 Mar 2. link to original article contains protocol PubMed
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
AC & Bevacizumab
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AC & Bevacizumab: Adriamycin (Doxorubicin), Cyclophosphamide, Bevacizumab
Variant #1, with range
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III (E) | AC | Superior PFS |
Chemotherapy
- Doxorubicin (Adriamycin) 50 to 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 8 cycles
Subsequent treatment
- Bevacizumab maintenance, if no PD
References
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
AT (Taxol)
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AT: Adriamycin (Doxorubicin) & Taxol (Paclitaxel)
Variant #1, 50/150
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sledge et al. 2003 (ECOG E1193) | Phase III (E) | 1. Doxorubicin 2. Paclitaxel |
Superior TTF |
Chemotherapy
- Doxorubicin (Adriamycin) as follows, given first:
- Cycles 1 to 8: 50 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 150 mg/m2 IV continuous infusion over 24 hours, started on day 1, given second, 3 hours after doxorubicin
21-day cycles
Variant #2, 50/220
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Jassem et al. 2001 | Phase III (E) | FAC | Seems to have superior OS |
Chemotherapy
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 220 mg/m2 IV over 3 hours once on day 2
21-day cycle for up to 8 cycles
Variant #3, 60/200
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Schmid et al. 2005 | Phase III (C) | Tandem auto HSCT | Seems not superior |
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV over 15 minutes once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1
21-day cycle for up to 6 cycles
Variant #4, with range
Study | Evidence |
---|---|
Gianni et al. 1995 | Non-randomized |
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 125 to 200 mg/m2 IV once on day 1
21-day cycles
References
- Gianni L, Munzone E, Capri G, Fulfaro F, Tarenzi E, Villani F, Spreafico C, Laffranchi A, Caraceni A, Martini C, Stefanelli M, Valagussa P, Bonadonna G. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol. 1995 Nov;13(11):2688-99. link to original article PubMed
- Jassem J, Pieńkowski T, Płuzańska A, Jelic S, Gorbunova V, Mrsic-Krmpotic Z, Berzins J, Nagykalnai T, Wigler N, Renard J, Munier S, Weil C; Central & Eastern Europe and Israel Pacitaxel Breast Cancer Study Group. Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial. J Clin Oncol. 2001 Mar 15;19(6):1707-15. link to original article contains protocol PubMed
- ECOG E1193: Sledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK, Wood WC. Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol. 2003 Feb 15;21(4):588-92. link to original article PubMed
- Schmid P, Schippinger W, Nitsch T, Huebner G, Heilmann V, Schultze W, Hausmaninger H, Wischnewsky M, Possinger K. Up-front tandem high-dose chemotherapy compared with standard chemotherapy with doxorubicin and paclitaxel in metastatic breast cancer: results of a randomized trial. J Clin Oncol. 2005 Jan 20;23(3):432-40. link to original article contains verified protocol PubMed
AT (Taxotere)
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AT: Adriamycin (Doxorubicin), Taxotere (Docetaxel)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Nabholtz et al. 2003 (TAX 306) | Phase III (E) | AC | Seems to have superior TTP |
Alba et al. 2004 (GEICAM-9903) | Phase III (C) | A, then T (Taxotere) | Seems not superior |
Bontenbal et al. 2005 | Phase III (E) | FAC | Seems to have superior OS |
Stemmler et al. 2010 (D4) | Phase III (C) | AT (Taxotere), weekly docetaxel | Seems not superior |
Chemotherapy
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for 6 cycles (GEICAM-9903 & Bontenbal et al. 2005) or 8 cycles (TAX 306 & D4)
References
- TAX 306: Nabholtz JM, Falkson C, Campos D, Szanto J, Martín M, Chan S, Pienkowski T, Zaluski J, Pinter T, Krzakowski M, Vorobiof D, Leonard R, Kennedy I, Azli N, Murawsky M, Riva A, Pouillart P; TAX 306 Study Group. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol. 2003 Mar 15;21(6):968-75. link to original article PubMed
- GEICAM-9903: Alba E, Martín M, Ramos M, Adrover E, Balil A, Jara C, Barnadas A, Fernández-Aramburo A, Sánchez-Rovira P, Amenedo M, Casado A; Spanish Breast Cancer Research Group. Multicenter randomized trial comparing sequential with concomitant administration of doxorubicin and docetaxel as first-line treatment of metastatic breast cancer: a Spanish Breast Cancer Research Group (GEICAM-9903) phase III study. J Clin Oncol. 2004 Jul 1;22(13):2587-93. link to original article contains protocol PubMed
- Bontenbal M, Creemers GJ, Braun HJ, de Boer AC, Janssen JT, Leys RB, Ruit JB, Goey SH, van der Velden PC, Kerkhofs LG, Schothorst KL, Schmitz PI, Bokma HJ, Verweij J, Seynaeve C; Dutch Community Setting Trial for the Clinical Trial Group. Phase II to III study comparing doxorubicin and docetaxel with fluorouracil, doxorubicin, and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: results of a Dutch Community Setting Trial for the Clinical Trial Group of the Comprehensive Cancer Centre. J Clin Oncol. 2005 Oct 1;23(28):7081-8. link to original article contains protocol PubMed
- D4: Stemmler HJ, Harbeck N, Gröll de Rivera I, Vehling Kaiser U, Rauthe G, Abenhardt W, Artmann A, Sommer H, Meerpohl HG, Kiechle M, Heinemann V. Prospective multicenter randomized phase III study of weekly versus standard docetaxel plus doxorubicin (D4) for first-line treatment of metastatic breast cancer. Oncology. 2010;79(3-4):204-10. Epub 2011 Mar 1. link to original article contains protocol PubMed
Capecitabine monotherapy
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Variant #1, 650 mg/m2 PO BID, continuous
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Stockler et al. 2011 (ANZ 0001) | Phase III (E) | 1. CMF | Seems to have superior OS |
2. Intermittent Capecitabine | Seems not superior |
Chemotherapy
- Capecitabine (Xeloda) 650 mg/m2 PO BID
21-day cycles
Variant #2, 1000 mg/m2 PO BID
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bajetta et al. 2005 | Phase II | ||
Robert et al. 2011 (RIBBON-1) | Phase III (C) | Capecitabine & Bevacizumab | Inferior PFS |
Stockler et al. 2011 (ANZ 0001) | Phase III (E) | 1. CMF | Seems to have superior OS |
2. Continuous Capecitabine | Seems not superior | ||
Smorenburg et al. 2014 (OMEGA) | Phase III (E) | PLD | Seems not superior |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
21-day cycle for 8 cycles (OMEGA) or indefinitely
Variant #3, 1250 mg/m2 PO BID
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bajetta et al. 2005 | Phase II | ||
Harbeck et al. 2016 (PELICAN) | Phase III (E) | Pegylated liposomal doxorubicin | Inconclusive whether non-inferior |
Robson et al. 2017 (OlympiAD) | Phase III (C) | Olaparib | Inferior PFS |
Patients in GBG 26/BIG 3-05 had HER2-positive disease. Patients in OlympiAD had confirmed deleterious or suspected deleterious germline BRCA mutation.
Preceding treatment
- JO21095: Docetaxel, with PD
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1 to 14
21-day cycles
References
- Bajetta E, Procopio G, Celio L, Gattinoni L, Della Torre S, Mariani L, Catena L, Ricotta R, Longarini R, Zilembo N, Buzzoni R. Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol. 2005 Apr 1;23(10):2155-61. Epub 2005 Feb 14. link to original article contains verified protocol PubMed
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
- ANZ 0001: Stockler MR, Harvey VJ, Francis PA, Byrne MJ, Ackland SP, Fitzharris B, Van Hazel G, Wilcken NR, Grimison PS, Nowak AK, Gainford MC, Fong A, Paksec L, Sourjina T, Zannino D, Gebski V, Simes RJ, Forbes JF, Coates AS. Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4498-504. Epub 2011 Oct 24. link to original article contains verified protocol PubMed
- OMEGA: Smorenburg CH, de Groot SM, van Leeuwen-Stok AE, Hamaker ME, Wymenga AN, de Graaf H, de Jongh FE, Braun JJ, Los M, Maartense E, van Tinteren H, Nortier JW, Seynaeve C. A randomized phase III study comparing pegylated liposomal doxorubicin with capecitabine as first-line chemotherapy in elderly patients with metastatic breast cancer: results of the OMEGA study of the Dutch Breast Cancer Research Group BOOG. Ann Oncol. 2014 Mar;25(3):599-605. Epub 2014 Feb 6. link to original article link to PMC article contains protocol PubMed
- PELICAN: Harbeck N, Saupe S, Jäger E, Schmidt M, Kreienberg R, Müller L, Otremba BJ, Waldenmaier D, Dorn J, Warm M, Scholz M, Untch M, de Wit M, Barinoff J, Lück HJ, Harter P, Augustin D, Harnett P, Beckmann MW, Al-Batran SE; PELICAN Investigators. A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. Breast Cancer Res Treat. 2017 Jan;161(1):63-72. Epub 2016 Oct 31. link to original article link to PMC article contains verified protocol PubMed
- OlympiAD: Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. link to original article contains verified protocol PubMed
Capecitabine & Bevacizumab
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III (E) | Capecitabine | Superior PFS |
Lang et al. 2013 (TURANDOT) | Phase III (E) | Paclitaxel & Bevacizumab | Non-inferior OS (*) |
Welt et al. 2016 (CARIN) | Phase III (C) | Capecitabine, Vinorelbine, Bevacizumab | Might have inferior PFS |
Note: efficacy for TURANDOT is based on the 2016 update.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
- TURANDOT: Lang I, Brodowicz T, Ryvo L, Kahan Z, Greil R, Beslija S, Stemmer SM, Kaufman B, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Messinger D, Zielinski C; Central European Cooperative Oncology Group. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial. Lancet Oncol. 2013 Feb;14(2):125-33. Epub 2013 Jan 10. link to original article PubMed
- Update: Zielinski C, Láng I, Inbar M, Kahán Z, Greil R, Beslija S, Stemmer SM, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Petruzelka L, Eniu A, Nisenbaum B, Dank M, Anghel R, Messinger D, Brodowicz T; TURANDOT investigators. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. Lancet Oncol. 2016 Sep;17(9):1230-9. Epub 2016 Aug 5. link to original article contains protocol PubMed
- CARIN: Welt A, Marschner N, Lerchenmueller C, Decker T, Steffens CC, Koehler A, Depenbusch R, Busies S, Hegewisch-Becker S. Capecitabine and bevacizumab with or without vinorelbine in first-line treatment of HER2/neu-negative metastatic or locally advanced breast cancer: final efficacy and safety data of the randomised, open-label superiority phase 3 CARIN trial. Breast Cancer Res Treat. 2016 Feb;156(1):97-107. link to PMC article PubMed
Capecitabine & Docetaxel
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CD: Capecitabine & Docetaxel
TX: Taxotere (Docetaxel) & Xeloda (Capecitabine)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Seidman et al. 2010 | Phase III (C) | GD | Seems not superior |
Wang et al. 2015 | Phase III (C) | NX | Inconclusive whether non-inferior |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for up to 8 cycles (Wang et al. 2015) or indefinitely
Subsequent treatment
- Seidman et al. 2010, upon progression: Gemcitabine
- Wang et al. 2015: Capecitabine maintenance
References
- Seidman AD, Brufsky A, Ansari RH, Hart LL, Stein RS, Schwartzberg LS, Stewart JF, Russell CA, Chen SC, Fein LE, De La Cruz Vargas JA, Kim SB, Cavalheiro J, Zhao L, Gill JF, Obasaju CK, Orlando M, Tai DF. Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel with planned crossover to the alternate single agent in metastatic breast cancer. Ann Oncol. 2011 May;22(5):1094-101. Epub 2010 Nov 17. link to original article contains protocol PubMed
- Wang J, Xu B, Yuan P, Ma F, Li Q, Zhang P, Cai R, Fan Y, Luo Y, Li Q. Capecitabine combined with docetaxel versus vinorelbine followed by capecitabine maintenance medication for first-line treatment of patients with advanced breast cancer: phase 3 randomized trial. Cancer. 2015 Oct 1;121(19):3412-21. Epub 2015 Jun 19. link to original article contains verified protocol PubMed
Capecitabine & Paclitaxel
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TX: Taxol (Paclitaxel), Xeloda (Capecitabine)
Regimen
Study | Evidence |
---|---|
Blum et al. 2006 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 (rounded to nearest 500 mg) PO BID on days 1 to 14
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Blum JL, Dees EC, Chacko A, Doane L, Ethirajan S, Hopkins J, McMahon R, Merten S, Negron A, Neubauer M, Ilegbodu D, Boehm KA, Asmar L, O'Shaughnessy JA. Phase II trial of capecitabine and weekly paclitaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2006 Sep 20;24(27):4384-90. Epub 2006 Aug 22. link to original article contains verified protocol PubMed
Capecitabine & Paclitaxel, nanoparticle albumin-bound
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Regimen
Study | Evidence |
---|---|
Schwartzberg et al. 2011 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 (rounded to nearest 500 mg) PO BID on days 1 to 15
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 125 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Schwartzberg LS, Arena FP, Mintzer DM, Epperson AL, Walker MS. Phase II multicenter trial of albumin-bound paclitaxel and capecitabine in first-line treatment of patients with metastatic breast cancer. Clin Breast Cancer. 2012 Apr;12(2):87-93. Epub 2011 Dec 6. link to original article contains protocol PubMed
CMF
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CMF: Cyclophosphamide, Methotrexate, Fluorouracil
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brambilla et al. 1976 | Phase III (C) | AV | Seems not superior |
Bull et al. 1978 | Phase III (C) | CAF | Might have inferior ORR |
Engelsman et al. 1991 (EORTC 10808) | Phase III (C) | CMF 600/40/600 (IV) | Seems to have superior OS |
Stadtmauer et al. 2000 (Philadelphia Bone Marrow Transplant Group) | Phase III (C) | CMF x 4-6, then HDT | Seems not superior |
Ackland et al. 2001 (HEPI 013) | Phase III (C) | CEF | Inferior TTP |
von Minckwitz et al. 2005 | Phase III (C) | BMF | Inferior TTP |
Stockler et al. 2011 (ANZ 0001) | Phase III (C) | 1. Continuous Capecitabine 2. Intermittent Capecitabine |
Seems to have inferior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV oncer per day on days 1 & 8
28-day cycles
References
- Brambilla C, De Lena M, Rossi A, Valagussa P, Bonadonna G. Response and survival in advanced breast cancer after two non-cross-resistant combinations. Br Med J. 1976 Apr 3;1(6013):801-4. link to PMC article PubMed
- Bull JM, Tormey DC, Li SH, Carbone PP, Falkson G, Blom J, Perlin E, Simon R. A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer. 1978 May;41(5):1649-57. link to original article PubMed
- EORTC 10808: Engelsman E, Klijn JC, Rubens RD, Wildiers J, Beex LV, Nooij MA, Rotmensz N, Sylvester R. "Classical" CMF versus a 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer: an EORTC Breast Cancer Co-operative Group Phase III Trial (10808). Eur J Cancer. 1991;27(8):966-70. link to original article contains verified protocol PubMed
- 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
- HEPI 013: Ackland SP, Anton A, Breitbach GP, Colajori E, Tursi JM, Delfino C, Efremidis A, Ezzat A, Fittipaldo A, Kolaric K, Lopez M, Viaro D; HEPI 013 study group. Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study. J Clin Oncol. 2001 Feb 15;19(4):943-53. link to original article PubMed
- von Minckwitz G, Chernozemsky I, Sirakova L, Chilingirov P, Souchon R, Marschner N, Kleeberg U, Tsekov C, Fritze D, Thomssen C, Stuart N, Vermorken JB, Loibl S, Merkle Kh, Kaufmann M. Bendamustine prolongs progression-free survival in metastatic breast cancer (MBC): a phase III prospective, randomized, multicenter trial of bendamustine hydrochloride, methotrexate and 5-fluorouracil (BMF) versus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as first-line treatment of MBC. Anticancer Drugs. 2005 Sep;16(8):871-7. link to original article PubMed
- ANZ 0001: Stockler MR, Harvey VJ, Francis PA, Byrne MJ, Ackland SP, Fitzharris B, Van Hazel G, Wilcken NR, Grimison PS, Nowak AK, Gainford MC, Fong A, Paksec L, Sourjina T, Zannino D, Gebski V, Simes RJ, Forbes JF, Coates AS. Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4498-504. Epub 2011 Oct 24. link to original article PubMed
DE
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DE: Docetaxel & Epirubicin
ED: Epirubicin & Docetaxel
ET: Epirubicin & Taxotere (Docetaxel)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bonneterre et al. 2004 | Randomized Phase II (E) | FEC | Superior ORR |
Mavroudis et al. 2009 | Phase III (C) | Capecitabine & Docetaxel | Seems not superior |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
21-day cycle for up to 8 cycles (Bonneterre et al. 2004) or indefinitely (Mavroudis et al. 2009)
References
- Bonneterre J, Dieras V, Tubiana-Hulin M, Bougnoux P, Bonneterre ME, Delozier T, Mayer F, Culine S, Dohoulou N, Bendahmane B. Phase II multicentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer. Br J Cancer. 2004 Oct 18;91(8):1466-71. link to original article link to PMC article contains protocol PubMed
- Mavroudis D, Papakotoulas P, Ardavanis A, Syrigos K, Kakolyris S, Ziras N, Kouroussis C, Malamos N, Polyzos A, Christophyllakis C, Kentepozidis N, Georgoulias V; Breast Cancer Investigators of the Hellenic Oncology Research Group. Randomized phase III trial comparing docetaxel plus epirubicin versus docetaxel plus capecitabine as first-line treatment in women with advanced breast cancer. Ann Oncol. 2010 Jan;21(1):48-54. Epub 2009 Nov 11. link to original article contains verified protocol PubMed
Docetaxel monotherapy
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D: Docetaxel
T: Taxotere (Docetaxel)
Variant #1, 40 mg/m2 3 weeks out of 4
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Rivera et al. 2008 | Phase III (E) | Docetaxel q3wk | Seems not superior | Superior toxicity |
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycle 1: 35 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
- Cycle 2 onwards: 40 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Variant #2, 40 mg/m2 6 weeks out of 8
Study | Evidence |
---|---|
Burstein et al. 2000 | Phase II |
Chemotherapy
- Docetaxel (Taxotere) 40 mg/m2 IV once per week for weeks 1 to 6
8-week cycles
Variant #3, 60 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Takashima et al. 2015 (SELECT BC) | Phase III (C) | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
21-day cycles
Variant #4, 60 mg/m2 q4wk
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Takashima et al. 2015 (SELECT BC) | Phase III (C) | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
28-day cycles
Variant #5, 75 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Sparano et al. 2009 (DOXIL-BCA-3001) | Phase III (C) | Docetaxel & PLD | Inferior TTP | Less toxic |
Robert et al. 2011 (RIBBON-1) | Phase III (C) | Docetaxel & Bevacizumab | Inferior PFS | |
Mackey et al. 2014 (ROSE/TRIO-12) | Phase III (C) | Docetaxel & Ramucirumab | Might have inferior PFS | |
Takashima et al. 2015 (SELECT BC) | Phase III (C) | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycles
Variant #6, 75 mg/m2 q4wk
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Takashima et al. 2015 (SELECT BC) | Phase III (C) | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
28-day cycles
Variant #7, 100 mg/m2
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Trudeau et al. 1996 | Phase II | |||
Marty et al. 2005 (M77001) | Phase III (C) | Docetaxel & Trastuzumab | Seems to have inferior OS | |
Rivera et al. 2008 | Phase III (C) | Weekly Docetaxel | Seems not superior | Inferior toxicity |
Gradishar et al. 2009 | Phase III (C) | 1. Higher-dose weekly nanoparticle albumin-bound paclitaxel | Inferior PFS | |
2. Lower-dose weekly nanoparticle albumin-bound paclitaxel | Seems not superior | |||
q3wk nanoparticle albumin-bound paclitaxel | Seems not superior | |||
Joensuu et al. 2009 | Phase III (C) | D/G | Seems not superior | More toxic |
Miles et al. 2010 (AVADO) | Phase III (C) | 1. Docetaxel & Bevacizumab (7.5 mg/kg) | Seems not superior | |
2. Docetaxel & Bevacizumab (15 mg/kg) | Inferior PFS | |||
Robert et al. 2011 (RIBBON-1) | Phase III (C) | Docetaxel & Bevacizumab | Inferior PFS | |
Nielsen et al. 2011 | Phase III (C) | Docetaxel & Gemcitabine | Might have inferior TTP | |
Bergh et al. 2012 (SUN 1064) | Phase III (C) | Docetaxel & Sunitinib | Seems not superior |
Note: AVADO gave up to 9 cycles.
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
- Note: Rivera et al. 2008 gave 75 mg/m2 in cycle 1, with escalation to 100 mg/m2 depending on toxicity
21-day cycles (see note)
References
- Trudeau ME, Eisenhauer EA, Higgins BP, Letendre F, Lofters WS, Norris BD, Vandenberg TA, Delorme F, Muldal AM. Docetaxel in patients with metastatic breast cancer: a phase II study of the National Cancer Institute of Canada-Clinical Trials Group. J Clin Oncol. 1996 Feb;14(2):422-8. link to original article contains protocol PubMed
- Review: Burris HA 3rd. Single-agent docetaxel (Taxotere) in randomized phase III trials. Semin Oncol. 1999 Jun;26(3 Suppl 9):1-6. PubMed
- Burstein HJ, Manola J, Younger J, Parker LM, Bunnell CA, Scheib R, Matulonis UA, Garber JE, Clarke KD, Shulman LN, Winer EP. Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol. 2000 Mar;18(6):1212-9. link to original article PubMed content property of HemOnc.org
- M77001: Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. 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 Jul 1;23(19):4265-74. Epub 2005 May 23. link to original article contains verified protocol PubMed
- Rivera E, Mejia JA, Arun BK, Adinin RB, Walters RS, Brewster A, Broglio KR, Yin G, Esmaeli B, Hortobagyi GN, Valero V. Phase 3 study comparing the use of docetaxel on an every-3-week versus weekly schedule in the treatment of metastatic breast cancer. Cancer. 2008 Apr 1;112(7):1455-61. link to original article contains verified protocol PubMed
- Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009 Aug 1;27(22):3611-9. Epub 2009 May 26. Erratum in: J Clin Oncol. 2011 Jul 1;29(19):2739. link to original article contains verified protocol PubMed
- DOXIL-BCA-3001: Sparano JA, Makhson AN, Semiglazov VF, Tjulandin SA, Balashova OI, Bondarenko IN, Bogdanova NV, Manikhas GM, Oliynychenko GP, Chatikhine VA, Zhuang SH, Xiu L, Yuan Z, Rackoff WR. Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. J Clin Oncol. 2009 Sep 20;27(27):4522-9. Epub 2009 Aug 17. link to original article contains verified protocol PubMed
- Joensuu H, Sailas L, Alanko T, Sunela K, Huuhtanen R, Utriainen M, Kokko R, Bono P, Wigren T, Pyrhönen S, Turpeenniemi-Hujanen T, Asola R, Leinonen M, Hahka-Kemppinen M, Kellokumpu-Lehtinen P. Docetaxel versus docetaxel alternating with gemcitabine as treatments of advanced breast cancer: final analysis of a randomised trial. Ann Oncol. 2010 May;21(5):968-73. Epub 2009 Oct 9. link to original article link to PMC article contains verified protocol PubMed
- AVADO: Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3239-47. Epub 2010 May 24. link to original article contains verified protocol PubMed
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
- Nielsen DL, Bjerre KD, Jakobsen EH, Cold S, Stenbygaard L, Sørensen PG, Kamby C, Møller S, Jørgensen CL, Andersson M. Gemcitabine plus docetaxel versus docetaxel in patients with predominantly human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: a randomized, phase III study by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2011 Dec 20;29(36):4748-54. Epub 2011 Nov 14. link to original article contains protocol PubMed
- SUN 1064: Bergh J, Bondarenko IM, Lichinitser MR, Liljegren A, Greil R, Voytko NL, Makhson AN, Cortes J, Lortholary A, Bischoff J, Chan A, Delaloge S, Huang X, Kern KA, Giorgetti C. First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study. J Clin Oncol. 2012 Mar 20;30(9):921-9. Epub 2012 Feb 13. link to original article contains verified protocol PubMed
- ROSE/TRIO-12: Mackey JR, Ramos-Vazquez M, Lipatov O, McCarthy N, Krasnozhon D, Semiglazov V, Manikhas A, Gelmon KA, Konecny GE, Webster M, Hegg R, Verma S, Gorbunova V, Abi Gerges D, Thireau F, Fung H, Simms L, Buyse M, Ibrahim A, Martín M. Primary results of ROSE/TRIO-12, a randomized placebo-controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer. J Clin Oncol. 2015 Jan 10;33(2):141-8. Epub 2014 Sep 2. link to original article contains protocol PubMed
- SELECT BC: Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. Epub 2015 Nov 27. link to original article contains verified protocol PubMed
- HRQoL analysis: Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Doihara H, Akabane H, Kashiwaba M, Watanabe T, Ohashi Y, Mukai H. Long-term health status as measured by EQ-5D among patients with metastatic breast cancer: comparison of first-line oral S-1 and taxane therapies in the randomized phase III SELECT BC trial. Qual Life Res. 2017 Feb;26(2):445-453. Epub 2016 Aug 12. link to original article link to PMC article PubMed
Docetaxel & Bevacizumab
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Variant #1, docetaxel 75 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III (E) | Docetaxel | Superior PFS |
Lück et al. 2014 (TABEA) | Phase III (C) | TBX | Seems not superior |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
Variant #2, docetaxel 100 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Miles et al. 2010 (AVADO) | Phase III (C) | 1. Docetaxel | Superior PFS |
2. Docetaxel & Bevacizumab (7.5 mg/kg) | Not reported | ||
Robert et al. 2011 (RIBBON-1) | Phase III (E) | Docetaxel | Superior PFS |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 9 cycles (AVADO) or indefinitely (RIBBON-1)
Subsequent treatment
- AVADO: Bevacizumab maintenance
References
- AVADO: Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3239-47. Epub 2010 May 24. link to original article contains verified protocol PubMed
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
- TABEA: Lück HJ, Lübbe K, Reinisch M, Maass N, Feisel-Schwickardi G, Tomé O, Janni W, Aydogdu M, Neunhöffer T, Ober A, Aktas B, Park-Simon TW, Schumacher C, Höffkes HG, Illmer T, Wagner H, Mehta K, von Minckwitz G, Nekljudova V, Loibl S. Phase III study on efficacy of taxanes plus bevacizumab with or without capecitabine as first-line chemotherapy in metastatic breast cancer. Breast Cancer Res Treat. 2015 Jan;149(1):141-9. Epub 2014 Dec 18. link to original article contains protocol PubMed
Docetaxel & Gemcitabine
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GD: Gemcitabine & Docetaxel
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Seidman et al. 2010 | Phase III (C) | CD | Seems not superior |
Nielsen et al. 2011 | Phase III (E) | Docetaxel | Might have superior TTP |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Nielsen et al. 2011 gave docetaxel on day 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycles
Subsequent treatment
- Seidman et al. 2010, upon progression: Capecitabine
References
- Fountzilas G, Dafni U, Dimopoulos MA, Koutras A, Skarlos D, Papakostas P, Gogas H, Bafaloukos D, Kalogera-Fountzila A, Samantas E, Briasoulis E, Pectasides D, Maniadakis N, Matsiakou F, Aravantinos G, Papadimitriou C, Karina M, Christodoulou C, Kosmidis P, Kalofonos HP. A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer: a Hellenic Cooperative Oncology Group study. Breast Cancer Res Treat. 2009 May;115(1):87-99. Epub 2008 May 16. link to original article contains verified protocol PubMed
- Seidman AD, Brufsky A, Ansari RH, Hart LL, Stein RS, Schwartzberg LS, Stewart JF, Russell CA, Chen SC, Fein LE, De La Cruz Vargas JA, Kim SB, Cavalheiro J, Zhao L, Gill JF, Obasaju CK, Orlando M, Tai DF. Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel with planned crossover to the alternate single agent in metastatic breast cancer. Ann Oncol. 2011 May;22(5):1094-101. Epub 2010 Nov 17. link to original article contains protocol PubMed
- Nielsen DL, Bjerre KD, Jakobsen EH, Cold S, Stenbygaard L, Sørensen PG, Kamby C, Møller S, Jørgensen CL, Andersson M. Gemcitabine plus docetaxel versus docetaxel in patients with predominantly human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: a randomized, phase III study by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2011 Dec 20;29(36):4748-54. Epub 2011 Nov 14. link to original article contains verified protocol PubMed
Doxorubicin monotherapy
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Variant #1, 20 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gundersen et al. 1986 | Phase III (E) | VAC | Seems not superior |
Chemotherapy
- Doxorubicin (Adriamycin) 20 mg/m2 IV once per week
Duration not specified
Variant #2, 60 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Norris et al. 2000 (NCIC CTG MA.8) | Phase III (C) | Doxorubicin & Vinorelbine | Seems not superior |
O'Brien et al. 2004 (CAELYX Breast Cancer Study Group) | Phase III (C) | Pegylated liposomal doxorubicin | Seems to have non-inferior PFS |
Note: in NCIC CTG MA.8, this dose was after a mid-protocol amendment. Treatment in NCIC CTG MA.8 was given until a cumulative dose of 450 mg/m2.
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
21-day cycles (see note)
Variant #3, 75 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Paridaens et al. 2000 (EORTC 10923) | Phase III (C) | Paclitaxel | Superior PFS |
Chemotherapy
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
21-day cycle for 7 cycles
References
- 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
- EORTC 10923: Paridaens R, Biganzoli L, Bruning P, Klijn JG, Gamucci T, Houston S, Coleman R, Schachter J, Van Vreckem A, Sylvester R, Awada A, Wildiers J, Piccart M. Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over. J Clin Oncol. 2000 Feb;18(4):724-33. link to original article contains protocol PubMed
- NCIC CTG MA.8: Norris B, Pritchard KI, James K, Myles J, Bennett K, Marlin S, Skillings J, Findlay B, Vandenberg T, Goss P, Latreille J, Rudinskas L, Lofters W, Trudeau M, Osoba D, Rodgers A. Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group study MA8. J Clin Oncol. 2000 Jun;18(12):2385-94. link to original article contains protocol PubMed
- CAELYX Breast Cancer Study Group: O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440-9. link to original article PubMed
Doxorubicin non-pegylated liposomal & Cyclophosphamide
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MC: Myocet (non-pegylated liposomal doxorubicin) & Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Lorusso et al. 2014 | Phase III (C) | NPLD & Vinorelbine | Seems not superior |
Chemotherapy
- Non-pegylated liposomal doxorubicin (Myocet) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycles
References
- Lorusso V, Giotta F, Bordonaro R, Maiello E, Del Prete S, Gebbia V, Filippelli G, Pisconti S, Cinieri S, Romito S, Riccardi F, Forcignanò R, Ciccarese M, Petrucelli L, Saracino V, Lupo LI, Gambino A, Leo S, Colucci G; Gruppo Oncologico Dell'Italia Meridionale. Non-pegylated liposome-encapsulated doxorubicin citrate plus cyclophosphamide or vinorelbine in metastatic breast cancer not previously treated with chemotherapy:a multicenter phase III study. Int J Oncol. 2014 Nov;45(5):2137-42. Epub 2014 Aug 18. link to original article contains protocol PubMed
Doxorubicin pegylated liposomal monotherapy
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Variant #1, 45 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Smorenburg et al. 2014 (OMEGA) | Phase III (E) | Capecitabine | Seems not superior |
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 45 mg/m2 IV once on day 1
28-day cycle for 6 cycles
Variant #2, 50 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
O'Brien et al. 2004 (CAELYX Breast Cancer Study Group) | Phase III (E) | Doxorubicin | Seems to have non-inferior PFS |
Harbeck et al. 2016 (PELICAN) | Phase III (E) | Capecitabine | Inconclusive whether non-inferior |
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 50 mg/m2 IV over up to 60 minutes once on day 1
- If infusion reactions occurred, infusion could be given over up to 90 minutes
28-day cycles
References
- CAELYX Breast Cancer Study Group: O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440-9. link to original article contains verified protocol PubMed
- OMEGA: Smorenburg CH, de Groot SM, van Leeuwen-Stok AE, Hamaker ME, Wymenga AN, de Graaf H, de Jongh FE, Braun JJ, Los M, Maartense E, van Tinteren H, Nortier JW, Seynaeve C. A randomized phase III study comparing pegylated liposomal doxorubicin with capecitabine as first-line chemotherapy in elderly patients with metastatic breast cancer: results of the OMEGA study of the Dutch Breast Cancer Research Group BOOG. Ann Oncol. 2014 Mar;25(3):599-605. Epub 2014 Feb 6. link to original article link to PMC article contains protocol PubMed
- PELICAN: Harbeck N, Saupe S, Jäger E, Schmidt M, Kreienberg R, Müller L, Otremba BJ, Waldenmaier D, Dorn J, Warm M, Scholz M, Untch M, de Wit M, Barinoff J, Lück HJ, Harter P, Augustin D, Harnett P, Beckmann MW, Al-Batran SE; PELICAN Investigators. A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. Breast Cancer Res Treat. 2017 Jan;161(1):63-72. Epub 2016 Oct 31. link to original article link to PMC article contains verified protocol PubMed
EC
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EC: Epirubicin & Cyclophosphamide
Variant #1, 75/600
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Slamon et al. 2001 | Phase III (C) | ECH | Seems to have inferior OS |
Chan et al. 2004 | Phase III (C) | MC | Seems to have inferior TTP |
Langley et al. 2005 (UKNCRI AB01) | Phase III (C) | EP | Seems not superior |
Note: patients in Slamon et al. 2001 had HER2+ disease.
Chemotherapy
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for up to 6 to 8 cycles
Variant #2, 90/600
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Blohmer et al. 2010 | Phase III (C) | ED | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for up to 6 to 8 cycles
Variant #3, with range
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III (C) | EC & Bevacizumab | Inferior PFS |
Chemotherapy
- Epirubicin (Ellence) 90 to 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for up to 8 cycles
References
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. link to original article PubMed
- Chan S, Davidson N, Juozaityte E, Erdkamp F, Pluzanska A, Azarnia N, Lee LW. Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer. Ann Oncol. 2004 Oct;15(10):1527-34. link to original article contains protocol PubMed
- UKNCRI AB01: Langley RE, Carmichael J, Jones AL, Cameron DA, Qian W, Uscinska B, Howell A, Parmar M. 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 Nov 20;23(33):8322-30. link to original article PubMed
- Blohmer JU, Schmid P, Hilfrich J, Friese K, Kleine-Tebbe A, Koelbl H, Sommer H, Morack G, Wischnewsky MB, Lichtenegger W, Kuemmel S. Epirubicin and cyclophosphamide versus epirubicin and docetaxel as first-line therapy for women with metastatic breast cancer: final results of a randomised phase III trial. Ann Oncol. 2010 Jul;21(7):1430-5. Epub 2010 Jan 20. link to original article contains protocol PubMed
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
EC & Bevacizumab
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EC & Bevacizumab: Epirubicin, Cyclophosphamide, Bevacizumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III (E) | EC | Superior PFS |
Chemotherapy
- Epirubicin (Ellence) 90 to 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 8 cycles
Subsequent treatment
- Bevacizumab maintenance, if no PD
References
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
EP
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EP: Epirubicin & Paclitaxel
ET: Epirubicin & Taxol (Paclitaxel)
Variant #1, 60/175
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Lück et al. 2013 | Phase III (C) | XP | Inconclusive whether non-inferior |
Chemotherapy
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for up to 6 cycles
Variant #2, 75/175
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hatschek et al. 2011 | Phase III (C) | TEX | Seems not superior |
Note: the doses of this regimen were individually adjusted after cycle 1; see paper for details.
Chemotherapy
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycles
Variant #3, 75/200
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Langley et al. 2005 (UKNCRI AB01) | Phase III (E) | EC | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
21-day cycle for up to 6 cycles
Variant #4, 80/175
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fountzilas et al. 2004 | Phase III (C) | Carboplatin & Paclitaxel | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 80 mg/m2 IV once on day 1, given second
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1, given first
21-day cycle for up to 6 cycles
Variant #5, 90/200
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Conte et al. 2004 | Phase III (C) | E, then P | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
21-day cycle for 8 cycles
References
- Conte PF, Guarneri V, Bruzzi P, Prochilo T, Salvadori B, Bolognesi A, Aldrighetti D, Venturini M, Rosso R, Mammoliti S, Carnino F, Giannessi P, Costantini M, Moyano A, Baldini E; Gruppo Oncologico Nord Ovest. Concomitant versus sequential administration of epirubicin and paclitaxel as first-line therapy in metastatic breast carcinoma: results for the Gruppo Oncologico Nord Ovest randomized trial. Cancer. 2004 Aug 15;101(4):704-12. link to original article contains protocol PubMed
- Fountzilas G, Kalofonos HP, Dafni U, Papadimitriou C, Bafaloukos D, Papakostas P, Kalogera-Fountzila A, Gogas H, Aravantinos G, Moulopoulos LA, Economopoulos T, Pectasides D, Maniadakis N, Siafaka V, Briasoulis E, Christodoulou C, Tsavdaridis D, Makrantonakis P, Razis E, Kosmidis P, Skarlos D, Dimopoulos MA. Paclitaxel and epirubicin versus paclitaxel and carboplatin as first-line chemotherapy in patients with advanced breast cancer: a phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol. 2004 Oct;15(10):1517-26. link to original article contains protocol PubMed
- UKNCRI AB01: Langley RE, Carmichael J, Jones AL, Cameron DA, Qian W, Uscinska B, Howell A, Parmar M. 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 Nov 20;23(33):8322-30. link to original article PubMed
- Hatschek T, Carlsson L, Einbeigi Z, Lidbrink E, Linderholm B, Lindh B, Loman N, Malmberg M, Rotstein S, Söderberg M, Sundquist M, Walz TM, Hellström M, Svensson H, Aström G, Brandberg Y, Carstensen J, Fernö M, Bergh J. Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial. Breast Cancer Res Treat. 2012 Feb;131(3):939-47. Epub 2011 Nov 18. link to original article contains protocol PubMed
- Lück HJ, Du Bois A, Loibl S, Schrader I, Huober J, Heilmann V, Beckmann M, Stähler A, Jackisch C, Hubalek M, Richter B, Stickeler E, Eidtmann H, Thomssen C, Untch M, Wollschläger K, Schuster T, von Minckwitz G. Capecitabine plus paclitaxel versus epirubicin plus paclitaxel as first-line treatment for metastatic breast cancer: efficacy and safety results of a randomized, phase III trial by the AGO Breast Cancer Study Group. Breast Cancer Res Treat. 2013 Jun;139(3):779-87. Epub 2013 Jun 15. link to original article contains protocol PubMed
Epirubicin monotherapy
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Variant #1, 35 mg/m2, 3 out of 4 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Feher et al. 2005 | Phase III (C) | Gemcitabine | Superior OS |
Chemotherapy
- Epirubicin (Ellence) 35 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Variant #2, 40 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bastholt et al. 1996 | Phase III (E) | 1. Epirubicin 60 mg/m2 | Seems not superior |
2. Epirubicin 90 mg/m2 | Inferior TTP | ||
3. Epirubicin 135 mg/m2 | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 40 mg/m2 IV once on day 1
21-day cycles
Variant #3, 60 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Nielsen et al. 1990 | Phase III (C) | Epirubicin & Vindesine | Seems not superior |
Bastholt et al. 1996 | Phase III (E) | 1. Epirubicin 40 mg/m2 | Seems not superior |
2. Epirubicin 90 mg/m2 | Seems not superior | ||
3. Epirubicin 135 mg/m2 | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
21-day cycles
Variant #4, 70 mg/m2, 2 out of 4 weeks
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Nielsen et al. 2000 | Phase III (C) | Cisplatin & Epirubicin | Seems to have inferior TTP | Superior toxicity |
Chemotherapy
- Epirubicin (Ellence) 70 mg/m2 IV once per day on days 1 & 8
28-day cycles until maximum dose of epirubicin reached (1000 mg/m2)
Variant #5, 90 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bastholt et al. 1996 | Phase III (C) | 1. Epirubicin 40 mg/m2 | Superior TTP |
2. Epirubicin 60 mg/m2 | Seems not superior | ||
3. Epirubicin 135 mg/m2 | Seems not superior | ||
Ejlertsen et al. 2004 (SBG 9403) | Phase III (C) | Epirubicin & Vinorelbine | Seems to have inferior PFS |
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
21-day cycles
Variant #6, 120 mg/m2, split doses
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Dogliotti et al. 1996 | Phase III (C) | Epirubicin & Lonidamine | Inferior ORR |
Berruti et al. 2002 | Phase III (C) | 1. Cisplatin & Epirubicin 2. Cisplatin, Epirubicin, Lonidamine 3. Epirubicin & Lonidamine |
Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 60 mg/m2 IV once per day on days 1 & 2
21-day cycles
Variant #7, 135 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bastholt et al. 1996 | Phase III (E) | 1. Epirubicin 40 mg/m2 | Seems not superior |
2. Epirubicin 60 mg/m2 | Seems not superior | ||
3. Epirubicin 90 mg/m2 | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 135 mg/m2 IV once on day 1
21-day cycles
References
- Nielsen D, Dombernowsky P, Skovsgaard T, Jensen J, Andersen E, Engelholm SA, Hansen M. Epirubicin or epirubicin and vindesine in advanced breast cancer: a phase III study. Ann Oncol. 1990 Jul;1(4):275-80. link to original article contains protocol PubMed
- Bastholt L, Dalmark M, Gjedde SB, Pfeiffer P, Pedersen D, Sandberg E, Kjaer M, Mouridsen HT, Rose C, Nielsen OS, Jakobsen P, Bentzen SM. Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: a randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 1996 Apr;14(4):1146-55. link to original article contains verified protocol PubMed
- Dogliotti L, Berruti A, Buniva T, Zola P, Baù MG, Farris A, Sarobba MG, Bottini A, Alquati P, Deltetto F, Gosso P, Monzeglio C, Moro G, Sussio M, Perroni D. Lonidamine significantly increases the activity of epirubicin in patients with advanced breast cancer: results from a multicenter prospective randomized trial. J Clin Oncol. 1996 Apr;14(4):1165-72. link to original article contains protocol PubMed
- Nielsen D, Dombernowsky P, Larsen SK, Hansen OP, Skovsgaard T. Epirubicin or epirubicin and cisplatin as first-line therapy in advanced breast cancer: a phase III study. Cancer Chemother Pharmacol. 2000;46(6):459-66. link to original article contains protocol PubMed
- Berruti A, Bitossi R, Gorzegno G, Bottini A, Alquati P, De Matteis A, Nuzzo F, Giardina G, Danese S, De Lena M, Lorusso V, Farris A, Sarobba MG, DeFabiani E, Bonazzi G, Castiglione F, Bumma C, Moro G, Bruzzi P, Dogliotti L; Epirubicin-Lonidamine Group Orbassano Torino Italy. Time to progression in metastatic breast cancer patients treated with epirubicin is not improved by the addition of either cisplatin or lonidamine: final results of a phase III study with a factorial design. J Clin Oncol. 2002 Oct 15;20(20):4150-9. link to original article contains protocol PubMed
- SBG 9403: Ejlertsen B, Mouridsen HT, Langkjer ST, Andersen J, Sjöström J, Kjaer M; Scandinavian Breast Group. Phase III study of intravenous vinorelbine in combination with epirubicin versus epirubicin alone in patients with advanced breast cancer: a Scandinavian Breast Group Trial (SBG9403). J Clin Oncol. 2004 Jun 15;22(12):2313-20. link to original article contains protocol PubMed
- Feher O, Vodvarka P, Jassem J, Morack G, Advani SH, Khoo KS, Doval DC, Ermisch S, Roychowdhury D, Miller MA, von Minckwitz G. First-line gemcitabine versus epirubicin in postmenopausal women aged 60 or older with metastatic breast cancer: a multicenter, randomized, phase III study. Ann Oncol. 2005 Jun;16(6):899-908. Epub 2005 Apr 8. link to original article contains protocol PubMed
FAC
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FAC: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide
CAF: Cyclophosphamide, Adriamycin (Doxorubicin), Fluorouracil
Variant #1, 500/50/500
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Smalley et al. 1977 | Phase III (E) | CMFVP | Might have superior OS (*) |
Muss et al. 1991 | Non-randomized portion of RCT | ||
Blajman et al. 1999 | Phase III (C) | NA | Seems not superior |
Jassem et al. 2001 | Phase III (C) | AT (Taxol) | Seems to have inferior OS |
Robert et al. 2011 (RIBBON-1) | Phase III (C) | FAC & Bevacizumab | Inferior PFS |
Note: reported efficacy for Smalley et al. 1977 is based on the 1983 update.
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for up to 6 to 8 cycles
Subsequent treatment
- Muss et al. 1991: CMF versus observation, then CMF at progression
Variant #2, 600/50/600
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Alonso et al. 1995 | Phase III (C) | CNF | Seems not superior |
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2/day IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for up to 10 cycles
Variant #3, 1000/40/500
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Aisner et al. 1995 (CALGB 8281) | Phase III (C) | 1. VATH 2. VATH/CMFVP |
Seems not superior |
Parnes et al. 2003 (CALGB 9140) | Phase III (C) | FAC & Leucovorin | Seems not superior |
Note: Aisner et al. 1995 does not describe dosing; included here because it is a CALGB study.
Chemotherapy
- Fluorouracil (5-FU) 200 mg/m2 IV once per day on days 1 to 5
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycles
Variant #4, 1000/50/500
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hortobagyi et al. 1979 | Phase III (C) | FAC-BCG | Inferior OS in responders |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8 or days 1 & 4
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycles
Variant #5, 1000/60/1400
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bull et al. 1978 | Phase III (E) | CMF | Might have superior ORR |
Sledge et al. 2000 (ECOG E3186) | Phase III (C) | CAFTH | Might have inferior TTF |
Pandya et al. 2007 (ECOG E3185) | Phase III (C) | CAF/TsAVbH | Seems not superior |
Note: the dosing details of ECOG E3185 are not described in the abstract.
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
28-day cycle for up to 6 cycles (ECOG E3186) or indefinitely (Bull et al. 1978)
References
- Smalley RV, Carpenter J, Bartolucci A, Vogel C, Krauss S. A comparison of cyclophosphamide, adriamycin, 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone (CMFVP) in patients with metastatic breast cancer: a Southeastern Cancer Study Group project. Cancer. 1977 Aug;40(2):625-32. link to original article contains verified protocol PubMed
- Update: Smalley RV, Lefante J, Bartolucci A, Carpenter J, Vogel C, Krauss S. A comparison of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) in patients with advanced breast cancer. Breast Cancer Res Treat. 1983;3(2):209-20. link to original article PubMed
- Bull JM, Tormey DC, Li SH, Carbone PP, Falkson G, Blom J, Perlin E, Simon R. A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer. 1978 May;41(5):1649-57. link to original article PubMed
- Hortobagyi GN, Gutterman JU, Blumenschein GR, Tashima CK, Burgess MA, Einhorn L, Buzdar AU, Richman SP, Hersh EM. Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG. Cancer. 1979 Nov;44(5):1955-62. link to original article PubMed
- Muss HB, Case LD, Richards F 2nd, White DR, Cooper MR, Cruz JM, Powell BL, Spurr CL, Capizzi RL; The Piedmont Oncology Association. Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. N Engl J Med. 1991 Nov 7;325(19):1342-8. link to original article contains verified protocol PubMed
- Alonso MC, Tabernero JM, Ojeda B, Llanos M, Solà C, Climent MA, Seguí MA, López JJ. A phase III randomized trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) versus cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) in patients with metastatic breast cancer. Breast Cancer Res Treat. 1995 Apr;34(1):15-24. link to original article contains protocol PubMed
- CALGB 8281: Aisner J, Cirrincione C, Perloff M, Perry M, Budman D, Abrams J, Panasci L, Muss H, Citron M, Holland J, Wood W, Henderson IC. Combination chemotherapy for metastatic or recurrent carcinoma of the breast--a randomized phase III trial comparing CAF versus VATH versus VATH alternating with CMFVP: Cancer and Leukemia Group B Study 8281. J Clin Oncol. 1995 Jun;13(6):1443-52. link to original article does not contain protocol PubMed
- Blajman C, Balbiani L, Block J, Coppola F, Chacon R, Fein L, Bonicatto S, Alvarez A, Schmilovich A, Delgado FM. A prospective, randomized Phase III trial comparing combination chemotherapy with cyclophosphamide, doxorubicin, and 5-fluorouracil with vinorelbine plus doxorubicin in the treatment of advanced breast carcinoma. Cancer. 1999 Mar 1;85(5):1091-7. link to original article contains verified protocol PubMed
- ECOG E3186: Sledge GW Jr, Hu P, Falkson G, Tormey D, Abeloff M. Comparison of chemotherapy with chemohormonal therapy as first-line therapy for metastatic, hormone-sensitive breast cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2000 Jan;18(2):262-6. link to original article contains verified protocol PubMed
- Jassem J, Pieńkowski T, Płuzańska A, Jelic S, Gorbunova V, Mrsic-Krmpotic Z, Berzins J, Nagykalnai T, Wigler N, Renard J, Munier S, Weil C; Central & Eastern Europe and Israel Pacitaxel Breast Cancer Study Group. Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial. J Clin Oncol. 2001 Mar 15;19(6):1707-15. link to original article contains protocol PubMed
- CALGB 9140: Parnes HL, Cirrincione C, Aisner J, Berry DA, Allen SL, Abrams J, Chuang E, Cooper MR, Perry MC, Duggan DB, Szatrowski TP, Henderson IC, Norton L; Cancer and Leukemia Group B. Phase III study of cyclophosphamide, doxorubicin, and fluorouracil (CAF) plus leucovorin versus CAF for metastatic breast cancer: Cancer and Leukemia Group B 9140. J Clin Oncol. 2003 May 1;21(9):1819-24. link to original article contains protocol PubMed
- ECOG E3185: Pandya KJ, Hu P, Osborne CK, Falkson G, Tormey DC; Eastern Cooperative Oncology Group. Phase III study of standard combination versus rotating regimen of induction chemotherapy in patients with hormone insensitive metastatic breast cancer: an Eastern Cooperative Oncology Group Intergroup Study (E3185). Am J Clin Oncol. 2007 Apr;30(2):113-25. link to original article PubMed
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
FAC & Bevacizumab
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FAC & Bevacizumab: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, Bevacizumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III (E) | FAC | Superior PFS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 8 cycles
Subsequent treatment
- Bevacizumab maintenance, if no PD
References
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
FEC
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FEC: Fluorouracil, Epirubicin, Cyclophosphamide
CEF: Cyclophosphamide, Epirubicin, Fluorouracil
Variant #1, 500/50/500 ("FEC50")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufman et al. 1997 (HEPI 010) | Phase III (C) | FEC 100 | Inferior ORR |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once once on day 1
21-day cycle for 6 to 8 cycles
Variant #2, 500/60/500
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Blomqvist et al. 1993 | Phase III (C) | Weekly FEC | Superior OS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once once on day 1
28-day cycles
Variant #3, 500/75/500 ("FEC75")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pacini et al. 2000 | Phase III (C) | EM +/- Lonidamine | Inferior OS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once once on day 1
21-day cycles
Variant #4, 500/90/500
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Zielinksi et al. 2005 (CECOG BM1) | Phase III (C) | GET | Seems not superior |
Robert et al. 2011 (RIBBON-1) | Phase III (C) | FEC & Bevacizumab | Inferior PFS |
Note: this is the lower bound of the dosing range allowed in RIBBON-1.
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once once on day 1
21-day cycle for up to 8 cycles
Variant #5, 500/100/500 ("FEC100")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufman et al. 1997 (HEPI 010) | Phase III (E) | FEC 50 | Superior ORR |
Robert et al. 2011 (RIBBON-1) | Phase III (C) | FEC & Bevacizumab | Inferior PFS |
Note: this is the upper bound of the dosing range allowed in RIBBON-1.
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once once on day 1
21-day cycle for 6 to 8 cycles
Variant #6, 600/60/600 ("CEF21")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Conte et al. 1996 | Phase III (C) | DES-CEF | Seems not superior |
Del Mastro et al. 2001 | Phase III (C) | HD-CEF14 | Seems not superior |
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once once on day 1
21-day cycle for 8 to 12 cycles
Variant #7, 1000/60/1400
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Esteban et al. 1999 | Phase III (C) | CNF | Seems to have superior OS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Epirubicin (Ellence) 30 mg/m2 IV once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
28-day cycles
Variant #8, 1000/100/800
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ackland et al. 2001 (HEPI 013) | Phase III (E) | CMF | Superior TTP |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Epirubicin (Ellence) 50 mg/m2 IV once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 400 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 to 8 cycles
References
- Blomqvist C, Elomaa I, Rissanen P, Hietanen P, Nevasaari K, Helle L. Influence of treatment schedule on toxicity and efficacy of cyclophosphamide, epirubicin, and fluorouracil in metastatic breast cancer: a randomized trial comparing weekly and every-4-week administration. J Clin Oncol. 1993 Mar;11(3):467-73. link to original article contains protocol PubMed
- Conte PF, Baldini E, Gardin G, Pronzato P, Amadori D, Carnino F, Monzeglio C, Gentilini P, Gallotti P, DeMicheli R, Venturini M, Rubagotti A, Rosso R. Chemotherapy with or without estrogenic recruitment in metastatic breast cancer: a randomized trial of the Gruppo Oncologico Nord Ovest (GONO). Ann Oncol. 1996 Jul;7(5):487-90. link to original article contains protocol PubMed
- HEPI 010: Brufman G, Colajori E, Ghilezan N, Lassus M, Martoni A, Perevodchikova N, Tosello C, Viaro D, Zielinski C; The Epirubicin High Dose (HEPI 010) Study Group. Doubling epirubicin dose intensity (100 mg/m2 versus 50 mg/m2) in the FEC regimen significantly increases response rates: an international randomised phase III study in metastatic breast cancer. Ann Oncol. 1997 Feb;8(2):155-62. link to original article contains verified protocol PubMed
- Estaban E, Lacave AJ, Fernández JL, Corral N, Buesa JM, Estrada E, Palacio I, Vieitez JM, Muñiz I, Alvarez E. Phase III trial of cyclophosphamide, epirubicin, fluorouracil (CEF) versus cyclophosphamide, mitoxantrone, fluorouracil (CNF) in women with metastatic breast cancer. Breast Cancer Res Treat. 1999 Nov;58(2):141-50. link to original article contains protocol PubMed
- Pacini P, Rinaldini M, Algeri R, Guarneri A, Tucci E, Barsanti G, Neri B, Bastiani P, Marzano S, Fallai C. FEC (5-fluorouracil, epidoxorubicin and cyclophosphamide) versus EM (epidoxorubicin and mitomycin-C) with or without lonidamine as first-line treatment for advanced breast cancer, a multicentric randomised study: final results. Eur J Cancer. 2000 May;36(8):966-75. link to original article contains protocol PubMed
- HEPI 013: Ackland SP, Anton A, Breitbach GP, Colajori E, Tursi JM, Delfino C, Efremidis A, Ezzat A, Fittipaldo A, Kolaric K, Lopez M, Viaro D; HEPI 013 study group. Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study. J Clin Oncol. 2001 Feb 15;19(4):943-53. link to original article contains protocol PubMed
- Del Mastro L, Venturini M, Lionetto R, Carnino F, Guarneri D, Gallo L, Contu A, Pronzato P, Vesentini L, Bergaglio M, Comis S, Rosso R. Accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with standard CEF in metastatic breast cancer patients: results of a multicenter, randomized phase III study of the Italian Gruppo Oncologico Nord-Ouest-Mammella Inter Gruppo Group. J Clin Oncol. 2001 Apr 15;19(8):2213-21. link to original article contains verified protocol PubMed
- CECOG BM1: Zielinski C, Beslija S, Mrsic-Krmpotic Z, Welnicka-Jaskiewicz M, Wiltschke C, Kahan Z, Grgic M, Tzekova V, Inbar M, Cervek J, Chernozemsky I, Szanto J, Spanik S, Wagnerova M, Ghilezan N, Pawlega J, Vrbanec D, Khamtsov D, Soldatenkova V, Brodowicz T. Gemcitabine, epirubicin, and paclitaxel versus fluorouracil, epirubicin, and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: a Central European Cooperative Oncology Group International, multicenter, prospective, randomized phase III trial. J Clin Oncol. 2005 Mar 1;23(7):1401-8. link to original article contains protocol PubMed
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
FEC & Bevacizumab
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FEC & Bevacizumab: Fluorouracil, Epirubicin, Cyclophosphamide, Bevacizumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III (E) | FEC | Superior PFS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 8 cycles
Subsequent treatment
- Bevacizumab maintenance, if no PD
References
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
Gemcitabine monotherapy
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Regimen
Study | Evidence |
---|---|
Carmichael et al. 1995 | Phase II, <20 pts in this subgroup |
Chemotherapy
- Gemcitabine (Gemzar) 800 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
References
- Carmichael J, Possinger K, Phillip P, Beykirch M, Kerr H, Walling J, Harris AL. Advanced breast cancer: a phase II trial with gemcitabine. J Clin Oncol. 1995 Nov;13(11):2731-6. link to original article contains protocol PubMed
Gemcitabine & Paclitaxel
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GT: Gemcitabine & Taxol (Paclitaxel)
PG: Paclitaxel & Gemcitabine
Variant #1, 6 cycles
Study | Evidence |
---|---|
Park et al. 2013 (KCSG-BR07-02) | Non-randomized portion of RCT |
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8, given second on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1, given first
21-day cycle for 6 cycles
Subsequent treatment
- Maintenance PG versus Observation
Variant #2, indefinite
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Albain et al. 2008 | Phase III (E) | Paclitaxel | Seems to have superior OS |
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 8, given second on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1, given first
21-day cycles
References
- Albain KS, Nag SM, Calderillo-Ruiz G, Jordaan JP, Llombart AC, Pluzanska A, Rolski J, Melemed AS, Reyes-Vidal JM, Sekhon JS, Simms L, O'Shaughnessy J. Gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol. 2008 Aug 20;26(24):3950-7. link to original article contains verified protocol PubMed
- KCSG-BR07-02: Park YH, Jung KH, Im SA, Sohn JH, Ro J, Ahn JH, Kim SB, Nam BH, Oh DY, Han SW, Lee S, Park IH, Lee KS, Kim JH, Kang SY, Lee MH, Park HS, Ahn JS, Im YH. Phase III, multicenter, randomized trial of maintenance chemotherapy versus observation in patients with metastatic breast cancer after achieving disease control with six cycles of gemcitabine plus paclitaxel as first-line chemotherapy: KCSG-BR07-02. J Clin Oncol. 2013 May 10;31(14):1732-9. Epub 2013 Apr 8. link to original article contains verified protocol PubMed
Paclitaxel monotherapy, weekly
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Variant #1, 80 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Perez et al. 2001 | Phase II | ||
Seidman et al. 2008 (CALGB 9840) | Phase III (E) | Paclitaxel q3wk | Superior OS |
Fountzilas et al. 2008 | Phase III (E) | 1. Carboplatin & Paclitaxel 2. Docetaxel & Gemcitabine |
Seems to have superior OS |
Martin et al. 2017 (BELLE-4) | Phase III (C) | Buparlisib & Paclitaxel | Seems not superior |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
28-day cycles
Variant #2, 80 mg/m2 3 weeks out of 4
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Guan et al. 2013 (EGF104535) | Phase III (C) | TL (Taxol) | Seems to have inferior OS | |
Takashima et al. 2015 (SELECT BC) | Phase III (C) | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Note: this is the lower limit of dosing allowed in SELECT BC. Patients in EGF104535 had HER2+ disease.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Variant #3, 90 mg/m2 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Miller et al. 2007 (ECOG 2100) | Phase III (C) | Paclitaxel & Bevacizumab | Inferior PFS |
Miles et al. 2016 (MERiDiAN) | Phase III (C) | Paclitaxel & Bevacizumab | Inferior PFS |
Chemotherapy
- Paclitaxel (Taxol) 90 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Variant #4, 100 mg/m2 weekly
Study | Evidence |
---|---|
Seidman et al. 1998 | Phase II, <20 pts in this subgroup |
Chemotherapy
- Paclitaxel (Taxol) 100 mg/m2 IV over 60 minutes once per week
Continued indefinitely
Variant #5, 100 mg/m2 3 weeks out of 4
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Takashima et al. 2015 (SELECT BC) | Phase III (C) | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Note: this is the upper limit of dosing allowed in SELECT BC.
Chemotherapy
- Paclitaxel (Taxol) 100 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- Seidman AD, Hudis CA, Albanell J, Tong W, Tepler I, Currie V, Moynahan ME, Theodoulou M, Gollub M, Baselga J, Norton L. Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol. 1998 Oct;16(10):3353-61. Erratum in: J Clin Oncol. 2006 May 10;24(14):2220. Albanel, J [corrected to Albanell, J ]. link to original article contains protocol PubMed
- Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001 Nov 15;19(22):4216-23. link to original article PubMed
- ECOG E2100: Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76. link to original article PubMed
- CALGB 9840: Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. 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 Apr 1;26(10):1642-9. link to original article PubMed
- Fountzilas G, Dafni U, Dimopoulos MA, Koutras A, Skarlos D, Papakostas P, Gogas H, Bafaloukos D, Kalogera-Fountzila A, Samantas E, Briasoulis E, Pectasides D, Maniadakis N, Matsiakou F, Aravantinos G, Papadimitriou C, Karina M, Christodoulou C, Kosmidis P, Kalofonos HP. A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer: a Hellenic Cooperative Oncology Group study. Breast Cancer Res Treat. 2009 May;115(1):87-99. Epub 2008 May 16. link to original article contains verified protocol PubMed
- EGF104535: Guan Z, Xu B, DeSilvio ML, Shen Z, Arpornwirat W, Tong Z, Lorvidhaya V, Jiang Z, Yang J, Makhson A, Leung WL, Russo MW, Newstat B, Wang L, Chen G, Oliva C, Gomez H. Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer. J Clin Oncol. 2013 Jun 1;31(16):1947-53. Epub 2013 Mar 18. link to original article contains verified protocol PubMed
- SELECT BC: Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. Epub 2015 Nov 27. link to original article contains verified protocol PubMed
- HRQoL analysis: Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Doihara H, Akabane H, Kashiwaba M, Watanabe T, Ohashi Y, Mukai H. Long-term health status as measured by EQ-5D among patients with metastatic breast cancer: comparison of first-line oral S-1 and taxane therapies in the randomized phase III SELECT BC trial. Qual Life Res. 2017 Feb;26(2):445-453. Epub 2016 Aug 12. link to original article link to PMC article PubMed
- MERiDiAN: Miles D, Cameron D, Bondarenko I, Manzyuk L, Alcedo JC, Lopez RI, Im SA, Canon JL, Shparyk Y, Yardley DA, Masuda N, Ro J, Denduluri N, Hubeaux S, Quah C, Bais C, O'Shaughnessy J. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer. 2017 Jan;70:146-155. Epub 2016 Nov 4. link to original article contains protocol PubMed
- Update: Miles D, Cameron D, Hilton M, Garcia J, O'Shaughnessy J. Overall survival in MERiDiAN, a double-blind placebo-controlled randomised phase III trial evaluating first-line bevacizumab plus paclitaxel for HER2-negative metastatic breast cancer. Eur J Cancer. 2018 Feb;90:153-155. Epub 2017 Nov 23. link to SD article PubMed
- BELLE-4: Martín M, Chan A, Dirix L, O'Shaughnessy J, Hegg R, Manikhas A, Shtivelband M, Krivorotko P, Batista López N, Campone M, Ruiz Borrego M, Khan QJ, Beck JT, Ramos Vázquez M, Urban P, Goteti S, Di Tomaso E, Massacesi C, Delaloge S. A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4). Ann Oncol. 2017 Feb 1;28(2):313-320. link to original article contains verified protocol PubMed
Paclitaxel monotherapy, q3wk
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Variant #1, 175 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Seidman et al. 1995 | Phase II | |||
Slamon et al. 2001 | Phase III (C) | TH | Seems to have inferior OS | |
Winer et al. 2004 (CALGB 9342) | Phase III (C) | 1. Paclitaxel 210 mg/m2 q3wk | Seems not superior | |
2. Paclitaxel 250 mg/m2 q3wk | Seems not superior | |||
Gradishar et al. 2005 | Phase III (C) | Nanoparticle albumin-bound paclitaxel | Inferior TTP | |
Seidman et al. 2008 (CALGB 9840) | Phase III (C) | Weekly paclitaxel | Inferior OS | |
Albain et al. 2008 | Phase III (C) | GT | Seems to have inferior OS | |
Di Leo et al. 2008 (EGF30001) | Phase III (C) | Lapatinib & Paclitaxel | Seems not superior | Less toxic |
Takashima et al. 2015 (SELECT BC) | Phase III (C) | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Park et al. 2016 | Phase III (C) | Genexol-PM | Seems to have non-inferior ORR |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
21-day cycles
Variant #2, 175 mg/m2 q4wk
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Takashima et al. 2015 (SELECT BC) | Phase III (C) | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
28-day cycles
Variant #3, 200 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bishop et al. 1999 | Phase III (E) | CMFP | Seems to have superior OS |
Paridaens et al. 2000 (EORTC 10923) | Phase III (E) | Doxorubicin | Inferior PFS |
Chemotherapy
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1
21-day cycle for 7 or 8 cycles
Variant #4, 250 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Holmes et al. 1991 | Phase II | ||
Smith et al. 1996 (NSABP B-26) | Phase III (C) | Paclitaxel 250 mg/m2 over 3 hours | Seems not superior |
Note: Holmes et al. 1991 is of historic interest, being the first phase II trial of a taxane in breast cancer.
Chemotherapy
- Paclitaxel (Taxol) 250 mg/m2 IV continuous infusion over 24 hours, started on day 1
21-day cycles
References
- Holmes FA, Walters RS, Theriault RL, Forman AD, Newton LK, Raber MN, Buzdar AU, Frye DK, Hortobagyi GN. Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst. 1991 Dec 18;83(24):1797-805. link to original article contains protocol PubMed
- Seidman AD, Tiersten A, Hudis C, Gollub M, Barrett S, Yao TJ, Lepore J, Gilewski T, Currie V, Crown J, Hakes T, Baselga J, Sklarin N, Moynihan ME, Tong W, Egorin M, Kearns C, Spriggs D, Norton L. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol. 1995 Oct;13(10):2575-81. link to original article PubMed
- Bishop JF, Dewar J, Toner GC, Smith J, Tattersall MH, Olver IN, Ackland S, Kennedy I, Goldstein D, Gurney H, Walpole E, Levi J, Stephenson J, Canetta R. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2355-64. link to original article contains protocol PubMed
- NSABP B-26: Smith RE, Brown AM, Mamounas EP, Anderson SJ, Lembersky BC, Atkins JH, Shibata HR, Baez L, DeFusco PA, Davila E, Tipping SJ, Bearden JD, Thirlwell MP. Randomized trial of 3-hour versus 24-hour infusion of high-dose paclitaxel in patients with metastatic or locally advanced breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-26. J Clin Oncol. 1999 Nov;17(11):3403-11. link to original article contains protocol PubMed
- EORTC 10923: Paridaens R, Biganzoli L, Bruning P, Klijn JG, Gamucci T, Houston S, Coleman R, Schachter J, Van Vreckem A, Sylvester R, Awada A, Wildiers J, Piccart M. Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over. J Clin Oncol. 2000 Feb;18(4):724-33. link to original article contains protocol PubMed
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. link to original article PubMed
- CALGB 9342: Winer EP, Berry DA, Woolf S, Duggan D, Kornblith A, Harris LN, Michaelson RA, Kirshner JA, Fleming GF, Perry MC, Graham ML, Sharp SA, Keresztes R, Henderson IC, Hudis C, Muss H, Norton L. Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: Cancer and Leukemia Group B trial 9342. J Clin Oncol. 2004 Jun 1;22(11):2061-8. link to original article contains protocol PubMed
- Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. Epub 2005 Sep 19. link to original article contains verified protocol PubMed
- CALGB 9840: Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. 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 Apr 1;26(10):1642-9. link to original article PubMed
- Albain KS, Nag SM, Calderillo-Ruiz G, Jordaan JP, Llombart AC, Pluzanska A, Rolski J, Melemed AS, Reyes-Vidal JM, Sekhon JS, Simms L, O'Shaughnessy J. Gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol. 2008 Aug 20;26(24):3950-7. link to original article PubMed
- EGF30001: Di Leo A, Gomez HL, Aziz Z, Zvirbule Z, Bines J, Arbushites MC, Guerrera SF, Koehler M, Oliva C, Stein SH, Williams LS, Dering J, Finn RS, Press MF. Phase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer. J Clin Oncol. 2008 Dec 1;26(34):5544-52. Epub 2008 Oct 27. Erratum in: J Clin Oncol. 2009 Apr 10;27(11):1923. link to original article link to PMC article contains protocol PubMed
- SELECT BC: Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. Epub 2015 Nov 27. link to original article contains verified protocol PubMed
- HRQoL analysis: Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Doihara H, Akabane H, Kashiwaba M, Watanabe T, Ohashi Y, Mukai H. Long-term health status as measured by EQ-5D among patients with metastatic breast cancer: comparison of first-line oral S-1 and taxane therapies in the randomized phase III SELECT BC trial. Qual Life Res. 2017 Feb;26(2):445-453. Epub 2016 Aug 12. link to original article link to PMC article PubMed
- Park IH, Sohn JH, Kim SB, Lee KS, Chung JS, Lee SH, Kim TY, Jung KH, Cho EK, Kim YS, Song HS, Seo JH, Ryoo HM, Lee SA, Yoon SY, Kim CS, Kim YT, Kim SY, Jin MR, Ro J. An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer. Cancer Res Treat. 2017 Jul;49(3):569-577. Epub 2016 Sep 12. link to original article link to PMC article contains protocol PubMed
Paclitaxel & Bevacizumab
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Miller et al. 2007 (ECOG E2100) | Phase III (E) | Paclitaxel | Superior PFS |
Robert et al. 2011 (SUN 1094) | Phase III (C) | Paclitaxel & Sunitinib | Seems not superior |
Lang et al. 2013 (TURANDOT) | Phase III (E) | Capecitabine & Bevacizumab | Non-inferior OS (*) |
Rugo et al. 2015 (CALGB 40502/NCCTG N063H) | Phase III (C) | 1. Ixabepilone & Bevacizumab | Superior PFS |
2. nab-Paclitaxel & Bevacizumab | Might have superior PFS | ||
Miles et al. 2016 (MERiDiAN) | Phase III (E) | Paclitaxel | Superior PFS |
Note: efficacy for TURANDOT is based on the 2016 update.
Chemotherapy
- Paclitaxel (Taxol) 90 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
References
- ECOG E2100: Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76. link to original article PubMed
- SUN 1094: Robert NJ, Saleh MN, Paul D, Generali D, Gressot L, Copur MS, Brufsky AM, Minton SE, Giguere JK, Smith JW 2nd, Richards PD, Gernhardt D, Huang X, Liau KF, Kern KA, Davis J. Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial. Clin Breast Cancer. 2011 Apr;11(2):82-92. Epub 2011 Apr 11. Erratum in: Clin Breast Cancer. 2011 Aug;11(4):273. link to original article link to PMC article contains verified protocol PubMed
- TURANDOT: Lang I, Brodowicz T, Ryvo L, Kahan Z, Greil R, Beslija S, Stemmer SM, Kaufman B, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Messinger D, Zielinski C; Central European Cooperative Oncology Group. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial. Lancet Oncol. 2013 Feb;14(2):125-33. Epub 2013 Jan 10. link to original article PubMed
- Update: Zielinski C, Láng I, Inbar M, Kahán Z, Greil R, Beslija S, Stemmer SM, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Petruzelka L, Eniu A, Nisenbaum B, Dank M, Anghel R, Messinger D, Brodowicz T; TURANDOT investigators. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. Lancet Oncol. 2016 Sep;17(9):1230-9. Epub 2016 Aug 5. link to original article contains protocol PubMed
- CALGB 40502/NCCTG N063H: Rugo HS, Barry WT, Moreno-Aspitia A, Lyss AP, Cirrincione C, Leung E, Mayer EL, Naughton M, Toppmeyer D, Carey LA, Perez EA, Hudis C, Winer EP. Randomized phase III trial of paclitaxel once per week compared with nanoparticle albumin-bound nab-paclitaxel once per week or ixabepilone with bevacizumab as first-line chemotherapy for locally recurrent or metastatic breast cancer: CALGB 40502/NCCTG N063H (Alliance). J Clin Oncol. 2015 Jul 20;33(21):2361-9. Epub 2015 Jun 8. link to original article contains verified protocol link to PMC article PubMed
- MERiDiAN: Miles D, Cameron D, Bondarenko I, Manzyuk L, Alcedo JC, Lopez RI, Im SA, Canon JL, Shparyk Y, Yardley DA, Masuda N, Ro J, Denduluri N, Hubeaux S, Quah C, Bais C, O'Shaughnessy J. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer. 2017 Jan;70:146-155. Epub 2016 Nov 4. link to original article contains protocol PubMed
- Update: Miles D, Cameron D, Hilton M, Garcia J, O'Shaughnessy J. Overall survival in MERiDiAN, a double-blind placebo-controlled randomised phase III trial evaluating first-line bevacizumab plus paclitaxel for HER2-negative metastatic breast cancer. Eur J Cancer. 2018 Feb;90:153-155. Epub 2017 Nov 23. link to SD article PubMed
Paclitaxel, nanoparticle albumin-bound monotherapy
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Example orders
Variant #1, 100 mg/m2, 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gradishar et al. 2009 | Randomized Phase II (E) | 1. Docetaxel | Seems not superior |
2. Weekly nab-paclitaxel (150 mg/m2) | Not reported | ||
3. q3wk nab-paclitaxel | Not reported |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Variant #2, 150 mg/m2 weekly, 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gradishar et al. 2009 | Randomized Phase II (E) | 1. Docetaxel | Superior PFS |
2. Weekly nab-paclitaxel (100 mg/m2) | Not reported | ||
3. q3wk nab-paclitaxel | Not reported |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 150 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Variant #3, 260 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gradishar et al. 2005 | Phase III (E) | Paclitaxel | Superior TTP |
Robert et al. 2011 (RIBBON-1) | Phase III (C) | nab-Paclitaxel & Bevacizumab | Inferior PFS |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m2 IV over 30 minutes once on day 1
Supportive medications
- Gradishar et al. 2005: No corticosteroid or antihistamine premedication
21-day cycles
Variant #4, 300 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gradishar et al. 2009 | Randomized Phase II (E) | 1. Docetaxel | Seems not superior |
2. Weekly nab-paclitaxel (100 mg/m2) | Not reported | ||
3. Weekly nab-paclitaxel (150 mg/m2) | Not reported |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 300 mg/m2 IV over 30 minutes once on day 1
21-day cycles
References
- Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. Epub 2005 Sep 19. link to original article contains verified protocol PubMed
- Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009 Aug 1;27(22):3611-9. Epub 2009 May 26. Erratum in: J Clin Oncol. 2011 Jul 1;29(19):2739. link to original article contains verified protocol PubMed
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
Paclitaxel, nanoparticle albumin-bound & Bevacizumab
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Example orders
Variant #1, 150 mg/m2, 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Rugo et al. 2015 (CALGB 40502/NCCTG N063H) | Phase III (E) | 1. Ixabepilone & Bevacizumab | Not reported |
2. Paclitaxel & Bevacizumab | Might have inferior PFS |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 150 mg/m2 IV once per day on days 1, 8, 15
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
Variant #2, 260 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III (E) | nab-Paclitaxel | Superior PFS |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
- CALGB 40502/NCCTG N063H: Rugo HS, Barry WT, Moreno-Aspitia A, Lyss AP, Cirrincione C, Leung E, Mayer EL, Naughton M, Toppmeyer D, Carey LA, Perez EA, Hudis C, Winer EP. Randomized phase III trial of paclitaxel once per week compared with nanoparticle albumin-bound nab-paclitaxel once per week or ixabepilone with bevacizumab as first-line chemotherapy for locally recurrent or metastatic breast cancer: CALGB 40502/NCCTG N063H (Alliance). J Clin Oncol. 2015 Jul 20;33(21):2361-9. Epub 2015 Jun 8. link to original article link to PMC article PubMed
Pemetrexed monotherapy
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Variant #1, 500 mg/m2
Study | Evidence |
---|---|
Gomez et al. 2006 | Phase II |
Patients in the study were "chemotherapy-naïve, with advanced (T4 and N0-N2, M0, M1) breast cancer."
Chemotherapy
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1
Supportive medications
- Dexamethasone (Decadron) 4 mg PO BID the day before, day of, and day after chemotherapy
- Folic acid 350 to 1000 mcg PO once per day, to start 5 to 7 days prior to start of pemetrexed therapy, to continue throughout therapy with pemetrexed
- Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, the first dose given before the study's pretreatment biopsy, to continue throughout therapy with pemetrexed
21-day cycle for up to 3 cycles
Variant #2, 600 mg/m2
Study | Evidence |
---|---|
Robert et al. 2011 | Phase II |
Chemotherapy
- Pemetrexed (Alimta) 600 mg/m2 IV once on day 1
Supportive medications
- Dexamethasone (Decadron) 4 mg PO BID the day before, day of, and day after chemotherapy
- Folic acid 350 to 1000 mcg PO once per day, to start at least 5 days prior to start of pemetrexed therapy, to continue throughout therapy with pemetrexed, and until 3 weeks after the last dose of pemetrexed
- Cyanocobalamin (Vitamin B12) 1000 mcg IM every 8 to 10 weeks, the first dose given at least 1 week prior to start of pemetrexed therapy, to continue throughout therapy with pemetrexed, and until 3 weeks after the last dose of pemetrexed
14-day cycles
References
- Gomez HL, Santillana SL, Vallejos CS, Velarde R, Sanchez J, Wang X, Bauer NL, Hockett RD, Chen VJ, Niyikiza C, Hanauske AR. A phase II trial of pemetrexed in advanced breast cancer: clinical response and association with molecular target expression. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):832-8. link to original article contains verified protocol PubMed
- Robert NJ, Conkling PR, O'Rourke MA, Kuefler PR, McIntyre KJ, Zhan F, Asmar L, Wang Y, Shonukan OO, O'Shaughnessy JA. Results of a phase II study of pemetrexed as first-line chemotherapy in patients with advanced or metastatic breast cancer. Breast Cancer Res Treat. 2011 Feb;126(1):101-8. Epub 2010 Dec 25. link to original article contains verified protocol PubMed
S-1 monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Takashima et al. 2015 (SELECT BC) | Phase III (E) | 1. Docetaxel 2. Paclitaxel |
Seems to have non-inferior OS | Superior EQ-5D score |
Chemotherapy
- Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m2: 40 mg PO BID on days 1 to 28
- BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO BID on days 1 to 28
- BSA 1.5 m2 or more: 60 mg PO BID on days 1 to 28
42-day cycles
References
- SELECT BC: Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. Epub 2015 Nov 27. link to original article contains verified protocol PubMed
- HRQoL analysis: Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Doihara H, Akabane H, Kashiwaba M, Watanabe T, Ohashi Y, Mukai H. Long-term health status as measured by EQ-5D among patients with metastatic breast cancer: comparison of first-line oral S-1 and taxane therapies in the randomized phase III SELECT BC trial. Qual Life Res. 2017 Feb;26(2):445-453. Epub 2016 Aug 12. link to original article link to PMC article PubMed
Metastatic disease, maintenance after first-line therapy
Bevacizumab monotherapy
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Regimen
Study | Evidence |
---|---|
Miles et al. 2010 (AVADO) | Non-randomized portion of RCT |
Robert et al. 2011 (RIBBON-1) | Non-randomized portion of RCT |
Preceding treatment
- AVADO: Docetaxel & Bev x 9
- RIBBON-1: AC & Bev x 8 or EC & Bev x 8 or FAC & Bev x 8 or FEC & Bev x 8
Chemotherapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- AVADO: Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3239-47. Epub 2010 May 24. link to original article contains verified protocol PubMed
- RIBBON-1: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
Gemcitabine & Paclitaxel
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GT: Gemcitabine & Taxol (Paclitaxel)
PG: Paclitaxel & Gemcitabine
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Park et al. 2013 (KCSG-BR07-02) | Phase III (E) | Observation | Seems to have superior OS |
Preceding treatment
- PG x 6
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8, given second on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1, given first
21-day cycles
References
- KCSG-BR07-02: Park YH, Jung KH, Im SA, Sohn JH, Ro J, Ahn JH, Kim SB, Nam BH, Oh DY, Han SW, Lee S, Park IH, Lee KS, Kim JH, Kang SY, Lee MH, Park HS, Ahn JS, Im YH. Phase III, multicenter, randomized trial of maintenance chemotherapy versus observation in patients with metastatic breast cancer after achieving disease control with six cycles of gemcitabine plus paclitaxel as first-line chemotherapy: KCSG-BR07-02. J Clin Oncol. 2013 May 10;31(14):1732-9. Epub 2013 Apr 8. link to original article contains verified protocol PubMed
Observation
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sparano et al. 2004 (ECOG E2196) | Phase III (C) | Marimastat | Seems not superior |
Alba et al. 2010 (GEICAM 2001-01) | Phase III (C) | PLD x 6 | Inferior TTP |
Park et al. 2013 (KCSG-BR07-02) | Phase III (C) | PG | Seems to have inferior OS |
No further treatment.
Preceding treatment
- ECOG E2196: Doxorubicin- and/or taxane-containing chemotherapy x 6-8
- GEICAM 2001-01: A x 3, then D x 3
- KCSG-BR07-02: PG x 6
References
- ECOG E2196: Sparano JA, Bernardo P, Stephenson P, Gradishar WJ, Ingle JN, Zucker S, Davidson NE. Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J Clin Oncol. 2004 Dec 1;22(23):4683-90. Erratum in: J Clin Oncol. 2005 Jan 1;23(1):248. link to original article PubMed
- GEICAM 2001-01: Alba E, Ruiz-Borrego M, Margelí M, Rodríguez-Lescure A, Sánchez-Rovira P, Ruiz A, Mel-Lorenzo JR, Ramos-Vázquez M, Ribelles N, Calvo E, Casado A, Márquez A, Vicente D, García-Sáenz JA, Martín M. Maintenance treatment with pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer: GEICAM 2001-01 study. Breast Cancer Res Treat. 2010 Jul;122(1):169-76. Epub 2010 Apr 2. link to original article PubMed
- KCSG-BR07-02: Park YH, Jung KH, Im SA, Sohn JH, Ro J, Ahn JH, Kim SB, Nam BH, Oh DY, Han SW, Lee S, Park IH, Lee KS, Kim JH, Kang SY, Lee MH, Park HS, Ahn JS, Im YH. Phase III, multicenter, randomized trial of maintenance chemotherapy versus observation in patients with metastatic breast cancer after achieving disease control with six cycles of gemcitabine plus paclitaxel as first-line chemotherapy: KCSG-BR07-02. J Clin Oncol. 2013 May 10;31(14):1732-9. Epub 2013 Apr 8. link to original article contains verified protocol PubMed
Metastatic disease, subsequent lines of chemotherapy
Abemaciclib monotherapy
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Regimen
FDA-recommended dose |
Study | Evidence | Efficacy |
---|---|---|
Dickler et al. 2017 (MONARCH 1) | Phase II | 20% (95% CI 13-27.5) |
Chemotherapy
- Abemaciclib (Verzenio) 200 mg PO BID
Continued indefinitely
References
- MONARCH 1: Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, Wildiers H, Hudis CA, O'Shaughnessy J, Zamora E, Yardley DA, Frenzel M, Koustenis A, Baselga J. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 Inhibitor, as a single agent, in patients with refractory HR(+)/HER2(-) metastatic breast cancer. Clin Cancer Res. 2017 Sep 1;23(17):5218-5224. Epub 2017 May 22. link to original article link to PMC article contains protocol PubMed
Capecitabine monotherapy
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Variant #1, 1000 mg/m2 PO BID
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Barrios et al. 2010 (SUN 1107) | Phase III (C) | Sunitinib | Superior PFS |
Brufsky et al. 2011 (RIBBON-2) | Phase III (C) | Capecitabine & Bevacizumab | Inferior PFS |
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | Capecitabine & Bevacizumab | Inferior PFS |
Baselga et al. 2017 (RESILIENCE) | Phase III (C) | Capecitabine & Sorafenib | Seems not superior |
Note: in SUN 1107, this dosage was used for patients older than 65 years.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
21-day cycles
Variant #2, 1250 mg/m2 PO BID
Patients in EGF100151 & GBG 26/BIG 3-05 had HER2-positive disease. Patients in OlympiAD had confirmed deleterious or suspected deleterious germline BRCA mutation. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm in this context.
Preceding treatment
- JO21095: Docetaxel, with PD
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1 to 14
21-day cycles
References
- Blum JL, Jones SE, Buzdar AU, LoRusso PM, Kuter I, Vogel C, Osterwalder B, Burger HU, Brown CS, Griffin T. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol. 1999 Feb;17(2):485-93. link to original article contains protocol PubMed
- Reichardt P, Von Minckwitz G, Thuss-Patience PC, Jonat W, Kölbl H, Jänicke F, Kieback DG, Kuhn W, Schindler AE, Mohrmann S, Kaufmann M, Lück HJ. Multicenter phase II study of oral capecitabine (Xeloda) in patients with metastatic breast cancer relapsing after treatment with a taxane-containing therapy. Ann Oncol. 2003 Aug;14(8):1227-33. link to original article contains protocol PubMed
- Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005 Feb 1;23(4):792-9. link to original article contains protocol PubMed
- EGF100151: Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. link to original article contains verified protocol PubMed
- Update: Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008 Dec;112(3):533-43. link to original article PubMed
- Update: Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15(9):924-34. link to original article link to PMC article PubMed
- CA163-046: Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Pivot XB, Klimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat LT, Roché HH. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210-7. link to original article contains verified protocol PubMed
- Update: Hortobagyi GN, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Lerzo GL, Pivot XB, Hurtado de Mendoza F, Xu B, Vahdat LT, Peck RA, Mukhopadhyay P, Roché HH. Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes. Breast Cancer Res Treat. 2010 Jul;122(2):409-18. Epub 2010 May 8. link to original article PubMed
- GBG 26/BIG 03-05: von Minckwitz G, du Bois A, Schmidt M, Maass N, Cufer T, de Jongh FE, Maartense E, Zielinski C, Kaufmann M, Bauer W, Baumann KH, Clemens MR, Duerr R, Uleer C, Andersson M, Stein RC, Nekljudova V, Loibl S. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German Breast Group 26/Breast International Group 03-05 study. J Clin Oncol. 2009 Apr 20;27(12):1999-2006. Epub 2009 Mar 16. link to original article contains verified protocol PubMed
- Update: von Minckwitz G, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, Maartense E, de Jongh FE, Baumann KH, Bischoff J, Harbeck N, Lück HJ, Maass N, Zielinski C, Andersson M, Stein RC, Nekljudova V, Loibl S; GBG 26/BIG 03-05 study group and participating investigators. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer. 2011 Oct;47(15):2273-81. Epub 2011 Jul 7. link to original article contains verified protocol PubMed
- SUN 1107: Barrios CH, Liu MC, Lee SC, Vanlemmens L, Ferrero JM, Tabei T, Pivot X, Iwata H, Aogi K, Lugo-Quintana R, Harbeck N, Brickman MJ, Zhang K, Kern KA, Martin M. Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer. Breast Cancer Res Treat. 2010 May;121(1):121-31. Epub 2010 Mar 26. link to original article link to PMC article contains protocol PubMed
- CA163-048: Sparano JA, Vrdoljak E, Rixe O, Xu B, Manikhas A, Medina C, Da Costa SC, Ro J, Rubio G, Rondinon M, Perez Manga G, Peck R, Poulart V, Conte P. Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2010 Jul 10;28(20):3256-63.link to original article contains verified protocol link to PMC article PubMed
- Pallis AG, Boukovinas I, Ardavanis A, Varthalitis I, Malamos N, Georgoulias V, Mavroudis D. A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer. Ann Oncol. 2012 May;23(5):1164-9. Epub 2011 Sep 21. link to original article contains protocol PubMed
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- A6181099: Crown JP, Diéras V, Staroslawska E, Yardley DA, Bachelot T, Davidson N, Wildiers H, Fasching PA, Capitain O, Ramos M, Greil R, Cognetti F, Fountzilas G, Blasinska-Morawiec M, Liedtke C, Kreienberg R, Miller WH Jr, Tassell V, Huang X, Paolini J, Kern KA, Romieu G. Phase III trial of sunitinib in combination with capecitabine versus capecitabine monotherapy for the treatment of patients with pretreated metastatic breast cancer. J Clin Oncol. 2013 Aug 10;31(23):2870-8. Epub 2013 Jul 15. link to original article contains verified protocol PubMed
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
- E7389-G000-301: Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20;33(6):594-601. Epub 2015 Jan 20. link to original article link to PMC article contains verified protocol PubMed
- JO21095: Yamamoto D, Sato N, Rai Y, Yamamoto Y, Saito M, Iwata H, Masuda N, Oura S, Watanabe J, Hattori S, Matsuura Y, Kuroi K. Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. Breast Cancer Res Treat. 2017 Feb;161(3):473-482. Epub 2016 Dec 22. link to original article contains verified protocol PubMed
- BG01-1323L: Zhang P, Sun T, Zhang Q, Yuan Z, Jiang Z, Wang XJ, Cui S, Teng Y, Hu XC, Yang J, Pan H, Tong Z, Li H, Yao Q, Wang Y, Yin Y, Sun P, Zheng H, Cheng J, Lu J, Zhang B, Geng C, Liu J, Peng R, Yan M, Zhang S, Huang J, Tang L, Qiu R, Xu B; BG01-1323L study group. Utidelone plus capecitabine versus capecitabine alone for heavily pretreated metastatic breast cancer refractory to anthracyclines and taxanes: a multicentre, open-label, superiority, phase 3, randomised controlled trial. Lancet Oncol. 2017 Mar;18(3):371-383. Epub 2017 Feb 11. link to original article contains protocol PubMed
- RESILIENCE: Baselga J, Zamagni C, Gómez P, Bermejo B, Nagai SE, Melichar B, Chan A, Mángel L, Bergh J, Costa F, Gómez HL, Gradishar WJ, Hudis CA, Rapoport BL, Roché H, Maeda P, Huang L, Meinhardt G, Zhang J, Schwartzberg LS. RESILIENCE: phase III randomized, double-blind trial comparing sorafenib with capecitabine versus placebo with capecitabine in locally advanced or metastatic HER2-negative breast cancer. Clin Breast Cancer. 2017 Dec;17(8):585-594.e4. Epub 2017 May 22. link to original article contains protocol PubMed
- OlympiAD: Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. link to original article contains verified protocol PubMed
Capecitabine & Bevacizumab
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III (E) | Capecitabine | Superior PFS |
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | Capecitabine | Superior PFS |
Note: efficacy for TURANDOT is based on the 2016 update.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Capecitabine & Docetaxel
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TX: Taxotere (Docetaxel) & Xeloda (Capecitabine)
XT: Xeloda (Capecitabine) & Taxotere (Docetaxel)
DC: Docetaxel & Capecitabine
Variant #1, 825/60
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Yamamoto et al. 2016 (JO21095) | Phase III (E) | Docetaxel | Seems to have superior PFS |
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 PO BID on days 1 to 14
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
21-day cycles
Variant #2, 1250/75
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
O'Shaughnessy et al. 2002 | Phase III (E) | Docetaxel | Seems to have superior OS |
Chan et al. 2009 | Phase III (C) | GD | Seems not superior |
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1 to 14
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
21-day cycles
References
- O'Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol. 2002 Jun 15;20(12):2812-23. link to original article contains verified protocol PubMed
- Chan S, Romieu G, Huober J, Delozier T, Tubiana-Hulin M, Schneeweiss A, Lluch A, Llombart A, du Bois A, Kreienberg R, Mayordomo JI, Antón A, Harrison M, Jones A, Carrasco E, Vaury AT, Frimodt-Moller B, Fumoleau P. Phase III study of gemcitabine plus docetaxel compared with capecitabine plus docetaxel for anthracycline-pretreated patients with metastatic breast cancer. J Clin Oncol. 2009 Apr 10;27(11):1753-60. Epub 2009 Mar 9. link to original article contains protocol PubMed
- JO21095: Yamamoto D, Sato N, Rai Y, Yamamoto Y, Saito M, Iwata H, Masuda N, Oura S, Watanabe J, Hattori S, Matsuura Y, Kuroi K. Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. Breast Cancer Res Treat. 2017 Feb;161(3):473-482. Epub 2016 Dec 22. link to original article contains verified protocol PubMed
Capecitabine & Ixabepilone
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XI: Xeloda (Capecitabine) & Ixabepilone
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Thomas et al. 2007 (CA163-046) | Phase III (E) | Capecitabine | Superior PFS |
Sparano et al. 2010 (CA163-048) | Phase III (E) | Capecitabine | Superior PFS |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
- Ixabepilone (Ixempra) 40 mg/m2 IV once on day 1
21-day cycles
References
- CA163-046: Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Pivot XB, Klimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat LT, Roché HH. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210-7. link to original article contains verified protocol PubMed
- Update: Hortobagyi GN, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Lerzo GL, Pivot XB, Hurtado de Mendoza F, Xu B, Vahdat LT, Peck RA, Mukhopadhyay P, Roché HH. Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes. Breast Cancer Res Treat. 2010 Jul;122(2):409-18. Epub 2010 May 8. link to original article PubMed
- CA163-048: Sparano JA, Vrdoljak E, Rixe O, Xu B, Manikhas A, Medina C, Da Costa SC, Ro J, Rubio G, Rondinon M, Perez Manga G, Peck R, Poulart V, Conte P. Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2010 Jul 10;28(20):3256-63. link to original article contains verified protocol link to PMC article PubMed
Carboplatin & Gemcitabine
back to top |
Regimen
Study | Evidence |
---|---|
Nagourney et al. 2008 | Pilot, <20 pts |
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV over 60 minutes once per day on days 1 & 8
- Gemcitabine (Gemzar) 800 mg/m2 IV over 60 minutes once per day on days 1 & 8
21-day cycles until CR or indefinitely
References
- Nagourney RA, Flam M, Link J, Hager S, Blitzer J, Lyons W, Sommers BL, Evans S. Carboplatin plus gemcitabine repeating doublet therapy in recurrent breast cancer. Clin Breast Cancer. 2008 Oct;8(5):432-5. link to original article contains protocol PubMed
Cisplatin & Vinorelbine
back to top |
Regimen
Study | Evidence |
---|---|
Ray-Coquard et al. 1998 | Phase II |
Vassilomanolakis et al. 2000 | Phase II |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
- Vinorelbine (Navelbine) 25 mg/m2 IV over 5 to 10 minutes once per day on days 1 & 8
Supportive medications
- Normal saline 200 mL bolus after Vinorelbine (Navelbine) to prevent phlebitis
- Normal saline 2000 mL with KCl (unspecified amount of KCl) IV over 4 hours (infusion rate: 500 mL/H) once prior to Cisplatin (Platinol)
- Furosemide (Lasix) 40 mg IV once 20 minutes prior to Cisplatin (Platinol)
- Normal saline 1000 mL and D5W 1000 mL IV over 4 hours (overall infusion rate: 500 mL/H; paper did not say whether fluids were given sequentially or concurrently) once after Cisplatin (Platinol)
- 5-HT3 antagonists used
21-day cycle for up to 6 cycles
References
- Ray-Coquard I, Biron P, Bachelot T, Guastalla JP, Catimel G, Merrouche Y, Droz JP, Chauvin F, Blay JY. Vinorelbine and cisplatin (CIVIC regimen) for the treatment of metastatic breast carcinoma after failure of anthracycline- and/or paclitaxel-containing regimens. Cancer. 1998 Jan 1;82(1):134-40. PubMed
- Vassilomanolakis M, Koumakis G, Barbounis V, Demiri M, Pateras H, Efremidis AP. Vinorelbine and cisplatin in metastatic breast cancer patients previously treated with anthracyclines. Ann Oncol. 2000 Sep;11(9):1155-60. link to original article contains verified protocol Pubmed
Docetaxel monotherapy
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D: Docetaxel
T: Taxotere (Docetaxel)
Variant #1, 40 mg/m2 3 weeks out of 4
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Rivera et al. 2008 | Phase III (C), <20 pts in this subgroup | Docetaxel q3wk | Seems not superior | Superior toxicity |
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycle 1: 35 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
- Cycle 2 onwards: 40 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Variant #2, 40 mg/m2 6 weeks out of 8
Study | Evidence |
---|---|
Burstein et al. 2000 | Phase II |
Chemotherapy
- Docetaxel (Taxotere) 40 mg/m2 IV once per week for weeks 1 to 6, then off for weeks 7 & 8
8-week cycles
Variant #3, 60 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Adachi et al. 1996 | Phase II | ||
Harvey et al. 2006 | Phase III (E) | 1. 75 mg/m2 q3wk docetaxel | Might have inferior TTP |
2. 100 mg/m2 q3wk docetaxel | Might have inferior TTP | ||
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | Docetaxel & Bevacizumab | Inferior PFS |
Note: this is the dosage used for Japanese patients; Adachi et al. 1996 reported 21- to 28-day cycles
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
21-day cycles
Variant #4, 70 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Yamamoto et al. 2016 (JO21095) | Phase III (C) | Capecitabine & Docetaxel | Seems to have inferior OS |
Chemotherapy
- Docetaxel (Taxotere) 70 mg/m2 IV once on day 1
21-day cycles
Subsequent treatment
- Upon progression: Capecitabine
Variant #5, 75 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Harvey et al. 2006 | Phase III (E) | 1. 60 mg/m2 q3wk docetaxel | Might have superior TTP |
2. 100 mg/m2 q3wk docetaxel | Might have inferior TTP | ||
Schröder et al. 2011 | Phase III (C) | Weekly docetaxel | Seems to have superior OS |
Brufsky et al. 2011 (RIBBON-2) | Phase III (C) | Docetaxel & Bevacizumab | Inferior PFS |
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | Docetaxel & Bevacizumab | Inferior PFS |
Note: Schröder et al. 2011 does not contain dosing information in the abstract. This is the lower end of the range of docetaxel dosing described in TANIA.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycles
Variant #6, 100 mg/m2
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
ten Bokkel Huinink et al. 1994 | Phase II | |||
Nabholtz et al. 1999 (TAX 304) | Phase III (E) | MV | Superior OS | |
Chan et al. 1999 (TAX 303) | Phase III (E) | Doxorubicin | Superior ORR | |
Sjöström et al. 1999 | Phase III (E) | MF | Superior TTP | |
O'Shaughnessy et al. 2002 | Phase III (C) | Capecitabine & Docetaxel | Seems to have inferior OS | |
Bonneterre et al. 2002 | Phase III (E) | 5-FU & Vinorelbine | Seems not superior | Less toxic |
Jones et al. 2005 | Phase III (E) | Paclitaxel | Seems to have superior OS | |
Harvey et al. 2006 | Phase III (E) | 1. 60 mg/m2 q3wk docetaxel | Might have superior TTP | |
2. 75 mg/m2 q3wk docetaxel | Might have superior TTP | |||
Rivera et al. 2008 | Phase III (C), <20 pts in this subgroup | Weekly Docetaxel | Seems not superior | Inferior toxicity |
Brufsky et al. 2011 (RIBBON-2) | Phase III (C) | Docetaxel & Bevacizumab | Inferior PFS | |
Nielsen et al. 2011 | Phase III (C) | Docetaxel & Gemcitabine | Might have inferior TTP | |
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | Docetaxel & Bevacizumab | Inferior PFS |
Note: this is the upper end of the range of docetaxel dosing described in TANIA. TAX 304 stopped treatment after 10 cycles. TAX 303 stopped treatment after 7 cycles.
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
- Note: Rivera et al. 2008 gave 75 mg/m2 in cycle 1, with escalation to 100 mg/m2 depending on toxicity
21-day cycles (see note)
References
- ten Bokkel Huinink WW, Prove AM, Piccart M, Steward W, Tursz T, Wanders J, Franklin H, Clavel M, Verweij J, Alakl M, Bayssas M, Kaye SB. A phase II trial with docetaxel (Taxotere) in second line treatment with chemotherapy for advanced breast cancer: a study of the EORTC Early Clinical Trials Group. Ann Oncol. 1994 Jul;5(6):527-32. link to original article contains protocol PubMed
- Adachi I, Watanabe T, Takashima S, Narabayashi M, Horikoshi N, Aoyama H, Taguchi T. A late phase II study of RP56976 (docetaxel) in patients with advanced or recurrent breast cancer. Br J Cancer. 1996 Jan;73(2):210-6. link to PMC article contains protocol PubMed
- TAX 304: Nabholtz JM, Senn HJ, Bezwoda WR, Melnychuk D, Deschênes L, Douma J, Vandenberg TA, Rapoport B, Rosso R, Trillet-Lenoir V, Drbal J, Molino A, Nortier JW, Richel DJ, Nagykalnai T, Siedlecki P, Wilking N, Genot JY, Hupperets PS, Pannuti F, Skarlos D, Tomiak EM, Murawsky M, Alakl M, Aapro M; 304 Study Group. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. J Clin Oncol. 1999 May;17(5):1413-24. link to original article contains protocol PubMed
- Review: Burris HA 3rd. Single-agent docetaxel (Taxotere) in randomized phase III trials. Semin Oncol. 1999 Jun;26(3 Suppl 9):1-6. PubMed
- TAX 303: Chan S, Friedrichs K, Noel D, Pintér T, Van Belle S, Vorobiof D, Duarte R, Gil Gil M, Bodrogi I, Murray E, Yelle L, von Minckwitz G, Korec S, Simmonds P, Buzzi F, González Mancha R, Richardson G, Walpole E, Ronzoni M, Murawsky M, Alakl M, Riva A, Crown J; 303 Study Group. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2341-54. link to original article PubMed
- Sjöström J, Blomqvist C, Mouridsen H, Pluzanska A, Ottosson-Lönn S, Bengtsson NO, Ostenstad B, Mjaaland I, Palm-Sjövall M, Wist E, Valvere V, Anderson H, Bergh J. Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group. Eur J Cancer. 1999 Aug;35(8):1194-201. link to original article contains protocol PubMed
- O'Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol. 2002 Jun 15;20(12):2812-23. link to original article contains verified protocol PubMed
- Bonneterre J, Roché H, Monnier A, Guastalla JP, Namer M, Fargeot P, Assadourian S. Docetaxel vs 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure. Br J Cancer. 2002 Nov 18;87(11):1210-5. link to original article contains protocol link to PMC article PubMed
- Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, Laufman L, Sundaram S, Urba WJ, Pritchard KI, Mennel R, Richards D, Olsen S, Meyers ML, Ravdin PM. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol. 2005 Aug 20;23(24):5542-51. link to original article contains protocol PubMed
- Harvey V, Mouridsen H, Semiglazov V, Jakobsen E, Voznyi E, Robinson BA, Groult V, Murawsky M, Cold S. Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol. 2006 Nov 1;24(31):4963-70. Epub 2006 Oct 10. link to original article PubMed
- Rivera E, Mejia JA, Arun BK, Adinin RB, Walters RS, Brewster A, Broglio KR, Yin G, Esmaeli B, Hortobagyi GN, Valero V. Phase 3 study comparing the use of docetaxel on an every-3-week versus weekly schedule in the treatment of metastatic breast cancer. Cancer. 2008 Apr 1;112(7):1455-61. link to original article contains verified protocol PubMed
- Schröder CP, de Munck L, Westermann AM, Smit WM, Creemers GJ, de Graaf H, Stouthard JM, van Deijk G, Erjavec Z, van Bochove A, Vader W, Willemse PH. Weekly docetaxel in metastatic breast cancer patients: no superior benefits compared to three-weekly docetaxel. Eur J Cancer. 2011 Jun;47(9):1355-62. Epub 2011 Jan 19. link to original article PubMed
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- Nielsen DL, Bjerre KD, Jakobsen EH, Cold S, Stenbygaard L, Sørensen PG, Kamby C, Møller S, Jørgensen CL, Andersson M. Gemcitabine plus docetaxel versus docetaxel in patients with predominantly human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: a randomized, phase III study by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2011 Dec 20;29(36):4748-54. Epub 2011 Nov 14. link to original article contains protocol PubMed
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
- JO21095: Yamamoto D, Sato N, Rai Y, Yamamoto Y, Saito M, Iwata H, Masuda N, Oura S, Watanabe J, Hattori S, Matsuura Y, Kuroi K. Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. Breast Cancer Res Treat. 2017 Feb;161(3):473-482. Epub 2016 Dec 22. link to original article contains verified protocol PubMed
Docetaxel & Bevacizumab
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Variant #1, docetaxel 60 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | Docetaxel | Superior PFS |
Note: this is the dosage used for Japanese patients.
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
Variant #2, docetaxel 75 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III (E) | Docetaxel | Superior PFS |
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | Docetaxel | Superior PFS |
Note: this is the lower end of the range of docetaxel dosing described in TANIA.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
Variant #3, docetaxel 100 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III (E) | Docetaxel | Superior PFS |
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | Docetaxel | Superior PFS |
Note: this is the upper end of the range of docetaxel dosing described in TANIA.
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Doxorubicin monotherapy
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Variant #1, 20 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | Doxorubicin & Bevacizumab | Inferior PFS |
Note: this is the lower end of the range of weekly doxorubicin dosing described in TANIA.
Chemotherapy
- Doxorubicin (Adriamycin) 20 mg/m2 IV once per week
Continued indefinitely
Variant #2, 25 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | Doxorubicin & Bevacizumab | Inferior PFS |
Note: this is the higher end of the range of weekly doxorubicin dosing described in TANIA.
Chemotherapy
- Doxorubicin (Adriamycin) 25 mg/m2 IV once per week
Continued indefinitely
Variant #3, 60 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Norris et al. 2000 (NCIC CTG MA.8) | Phase III (C) | Doxorubicin & Vinorelbine | Seems not superior |
Reyno et al. 2004 (NCIC CT MA.19) | Phase III (C) | Doxorubicin & Tesmilifene | Seems not superior |
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | Doxorubicin & Bevacizumab | Inferior PFS |
Note: in NCIC CTG MA.8, this dose was after a mid-protocol amendment. Treatment in NCIC CTG MA.8 & MA.19 was given until a cumulative dose of 450 mg/m2. This is the lower end of the range of q3wk doxorubicin dosing described in TANIA.
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
21-day cycles (see note)
Variant #4, 75 mg/m2 q3wk, limited duration
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Chan et al. 1999 (TAX 303) | Phase III (C) | Docetaxel | Inferior ORR |
Chemotherapy
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
21-day cycle for up to 7 cycles
Variant #5, 75 mg/m2 q3wk, indefinite
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bontenbal et al. 1998 | Phase III (C) | Epirubicin | Seems not superior |
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | Doxorubicin & Bevacizumab | Inferior PFS |
Note: this is the higher end of the range of q3wk doxorubicin dosing described in TANIA.
Chemotherapy
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
21-day cycles
References
- Bontenbal M, Andersson M, Wildiers J, Cocconi G, Jassem J, Paridaens R, Rotmensz N, Sylvester R, Mouridsen HT, Klijn JG, van Oosterom AT; EORTC Breast Cancer Cooperative Group. Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study in advanced breast cancer. Br J Cancer. 1998 Jun;77(12):2257-63. link to original article link to PMC article contains protocol PubMed
- TAX 303: Chan S, Friedrichs K, Noel D, Pintér T, Van Belle S, Vorobiof D, Duarte R, Gil Gil M, Bodrogi I, Murray E, Yelle L, von Minckwitz G, Korec S, Simmonds P, Buzzi F, González Mancha R, Richardson G, Walpole E, Ronzoni M, Murawsky M, Alakl M, Riva A, Crown J; 303 Study Group. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2341-54. link to original article PubMed
- NCIC CTG MA.8: Norris B, Pritchard KI, James K, Myles J, Bennett K, Marlin S, Skillings J, Findlay B, Vandenberg T, Goss P, Latreille J, Rudinskas L, Lofters W, Trudeau M, Osoba D, Rodgers A. Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group study MA8. J Clin Oncol. 2000 Jun;18(12):2385-94. link to original article contains protocol PubMed
- NCIC CT MA.19: Reyno L, Seymour L, Tu D, Dent S, Gelmon K, Walley B, Pluzanska A, Gorbunova V, Garin A, Jassem J, Pienkowski T, Dancey J, Pearce L, MacNeil M, Marlin S, Lebwohl D, Voi M, Pritchard K; National Cancer Institute of Canada Clinical Trials Group Study MA.19. Phase III study of N,N-diethyl-2-[4-(phenylmethyl) phenoxy]ethanamine (BMS-217380-01) combined with doxorubicin versus doxorubicin alone in metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA.19. J Clin Oncol. 2004 Jan 15;22(2):269-76. link to original article PubMed
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Doxorubicin & Bevacizumab
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Variant #1, doxorubicin 20 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | Doxorubicin | Superior PFS |
Note: this is the lower end of the range of weekly doxorubicin dosing described in TANIA.
Chemotherapy
- Doxorubicin (Adriamycin) 20 mg/m2 IV once per week
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
Variant #2, doxorubicin 25 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | Doxorubicin | Superior PFS |
Note: this is the higher end of the range of weekly doxorubicin dosing described in TANIA.
Chemotherapy
- Doxorubicin (Adriamycin) 25 mg/m2 IV once per week
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
Variant #3, doxorubicin 60 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | Doxorubicin | Superior PFS |
Note: this is the lower end of the range of q3wk doxorubicin dosing described in TANIA.
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
Variant #4, doxorubicin 75 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | Doxorubicin | Superior PFS |
Note: this is the higher end of the range of q3wk doxorubicin dosing described in TANIA.
Chemotherapy
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Doxorubicin non-pegylated liposomal monotherapy
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NPLD: Non-Pegylated Liposomal Doxorubicin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | NPLD & Bevacizumab | Inferior PFS |
Chemotherapy
- Non-pegylated liposomal doxorubicin (Myocet) 60 mg/m2 IV once on day 1
21-day cycles
References
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Doxorubicin non-pegylated liposomal & Bevacizumab
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NPLD/Bev: Non-Pegylated Liposomal Doxorubicin & Bevacizumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | NPLD | Superior PFS |
Chemotherapy
- Non-pegylated liposomal doxorubicin (Myocet) 60 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Doxorubicin pegylated liposomal monotherapy
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PLD: Pegylated Liposomal Doxorubicin
Variant #1, 40 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | PLD & Bevacizumab | Inferior PFS |
Note: this is the lower end of the range of pegylated liposomal doxorubicin dosing described in TANIA.
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 40 mg/m2 IV once on day 1
28-day cycles
Variant #2, 50 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Keller et al. 2004 | Phase III (E) | 1. Mitomycin & Vinblastine 2. Vinorelbine |
Seems not superior |
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | PLD & Bevacizumab | Inferior PFS |
Note: this is the higher end of the range of pegylated liposomal doxorubicin dosing described in TANIA.
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 50 mg/m2 IV once on day 1
28-day cycles
References
- Keller AM, Mennel RG, Georgoulias VA, Nabholtz JM, Erazo A, Lluch A, Vogel CL, Kaufmann M, von Minckwitz G, Henderson IC, Mellars L, Alland L, Tendler C. Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. J Clin Oncol. 2004 Oct 1;22(19):3893-901. link to original article contains protocol PubMed
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Doxorubicin pegylated liposomal & Bevacizumab
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PLD/Bev: Pegylated Liposomal Doxorubicin & Bevacizumab
Variant #1, 40 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | PLD | Superior PFS |
Note: this is the lower end of the range of pegylated liposomal doxorubicin dosing described in TANIA.
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 40 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
Variant #2, 50 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | PLD | Superior PFS |
Note: this is the higher end of the range of pegylated liposomal doxorubicin dosing described in TANIA.
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 50 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
References
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Eribulin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Cortes et al. 2011 (EMBRACE) | Phase III (E) | Investigator's choice | Seems to have superior OS |
Kaufman et al. 2015 (E7389-G000-301) | Phase III (E) | Capecitabine | Might have superior OS |
Robson et al. 2017 (OlympiAD) | Phase III (C) | Olaparib | Inferior PFS |
Patients in OlympiAD had confirmed deleterious or suspected deleterious germline BRCA mutation.
Chemotherapy
- Eribulin (Halaven) 1.4 mg/m2 IV over 2 to 5 minutes once per day on days 1 & 8
21-day cycles
References
- EMBRACE: Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Diéras V, Delozier T, Vladimirov V, Cardoso F, Koh H, Bougnoux P, Dutcus CE, Seegobin S, Mir D, Meneses N, Wanders J, Twelves C; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011 Mar 12;377(9769):914-23. Epub 2011 Mar 2. link to original article contains protocol PubMed
- E7389-G000-301: Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20;33(6):594-601. Epub 2015 Jan 20. link to original article link to PMC article contains verified protocol PubMed
- OlympiAD: Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. link to original article contains verified protocol PubMed
Gemcitabine monotherapy
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Variant #1, 800 mg/m2 3 weeks out of 4
Study | Evidence |
---|---|
Carmichael et al. 1995 | Phase II |
Chemotherapy
- Gemcitabine (Gemzar) 800 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Variant #2, 1000 mg/m2 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | Gemcitabine & Bevacizumab | Inferior PFS |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Variant #3, 1200 mg/m2 3 weeks out of 4
Study | Evidence |
---|---|
Spielmann et al. 2001 | Phase II |
Chemotherapy
- Gemcitabine (Gemzar) 1200 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Variant #4, 1250 mg/m2 2 weeks out of 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III (C) | Gemcitabine & Bevacizumab | Inferior PFS |
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | Gemcitabine & Bevacizumab | Inferior PFS |
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycles
References
- Carmichael J, Possinger K, Phillip P, Beykirch M, Kerr H, Walling J, Harris AL. Advanced breast cancer: a phase II trial with gemcitabine. J Clin Oncol. 1995 Nov;13(11):2731-6. link to original article contains protocol PubMed
- Spielmann M, Llombart-Cussac A, Kalla S, Espié M, Namer M, Ferrero JM, Diéras V, Fumoleau P, Cuvier C, Perrocheau G, Ponzio A, Kayitalire L, Pouillart P. Single-agent gemcitabine is active in previously treated metastatic breast cancer. Oncology. 2001;60(4):303-7. link to original article PubMed
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Gemcitabine & Bevacizumab
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Variant #1, 1000 mg/m2, 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | Gemcitabine | Superior PFS |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
Variant #2, 1250 mg/m2, 2 weeks out of 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III (E) | Gemcitabine | Superior PFS |
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | Gemcitabine | Superior PFS |
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Paclitaxel monotherapy, weekly
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Variant #1, 80 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Perez et al. 2001 | Phase II | ||
Seidman et al. 2008 (CALGB 9840) | Phase III (E) | Paclitaxel q3wk | Superior OS |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
28-day cycles
Variant #2, 90 mg/m2 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III (C) | Paclitaxel & Bevacizumab | Inferior PFS |
Chemotherapy
- Paclitaxel (Taxol) 90 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001 Nov 15;19(22):4216-23. link to original article PubMed
- CALGB 9840: Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. 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 Apr 1;26(10):1642-9. link to original article PubMed
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
Paclitaxel monotherapy, q3wk
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Variant #1, 135 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Nabholtz et al. 1996 | Phase III (E) | Paclitaxel 175 mg/m2 q3wk | Seems not superior (*) |
Note: although Nabholtz et al. 1996 did not meet its primary endpoint, there seemed to be a TTP disadvantage in the lower-dose arm.
Chemotherapy
- Paclitaxel (Taxol) 135 mg/m2 IV over 3 hours once on day 1
21-day cycles
Variant #2, 175 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Seidman et al. 1995 | Phase II | ||
Nabholtz et al. 1996 | Phase III (E) | Paclitaxel 135 mg/m2 q3wk | Seems not superior (*) |
Winer et al. 2004 (CALGB 9342) | Phase III (C) | 1. Paclitaxel 210 mg/m2 q3wk | Seems not superior |
2. Paclitaxel 250 mg/m2 q3wk | Seems not superior | ||
Icli et al. 2005 | Phase III (C) | EoP | Seems to have inferior OS |
Jones et al. 2005 | Phase III (E) | Docetaxel | Seems to have inferior OS |
Gradishar et al. 2005 | Phase III (C) | Nanoparticle albumin-bound paclitaxel | Inferior TTP |
Seidman et al. 2008 (CALGB 9840) | Phase III (C) | Weekly paclitaxel | Inferior OS |
Brufsky et al. 2011 (RIBBON-2) | Phase III (C) | Paclitaxel & Bevacizumab | Inferior PFS |
Note: although Nabholtz et al. 1996 did not meet its primary endpoint, there seemed to be a TTP advantage in the higher-dose arm, which subsequently led to its adoption as the standard-of-care.
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
21-day cycles
References
- Seidman AD, Tiersten A, Hudis C, Gollub M, Barrett S, Yao TJ, Lepore J, Gilewski T, Currie V, Crown J, Hakes T, Baselga J, Sklarin N, Moynihan ME, Tong W, Egorin M, Kearns C, Spriggs D, Norton L. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol. 1995 Oct;13(10):2575-81. link to original article PubMed
- Nabholtz JM, Gelmon K, Bontenbal M, Spielmann M, Catimel G, Conte P, Klaassen U, Namer M, Bonneterre J, Fumoleau P, Winograd B. Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol. 1996 Jun;14(6):1858-67. link to original article contains protocol PubMed
- CALGB 9342: Winer EP, Berry DA, Woolf S, Duggan D, Kornblith A, Harris LN, Michaelson RA, Kirshner JA, Fleming GF, Perry MC, Graham ML, Sharp SA, Keresztes R, Henderson IC, Hudis C, Muss H, Norton L. Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: Cancer and Leukemia Group B trial 9342. J Clin Oncol. 2004 Jun 1;22(11):2061-8. link to original article contains protocol PubMed
- Icli F, Akbulut H, Uner A, Yalcin B, Baltali E, Altinbas M, Coşkun S, Komurcu S, Erkisi M, Demirkazik A, Senler FC, Sencan O, Büyükcelik A, Boruban C, Onur H, Zengin N, Sak SD. Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group. Br J Cancer. 2005 Feb 28;92(4):639-44. link to original article link to PMC article contains protocol PubMed
- Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, Laufman L, Sundaram S, Urba WJ, Pritchard KI, Mennel R, Richards D, Olsen S, Meyers ML, Ravdin PM. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol. 2005 Aug 20;23(24):5542-51. link to original article contains protocol PubMed
- Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. Epub 2005 Sep 19. link to original article contains verified protocol PubMed
- CALGB 9840: Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. 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 Apr 1;26(10):1642-9. link to original article PubMed
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
Paclitaxel & Bevacizumab
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Variant #1, 90 mg/m2 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III (E) | Paclitaxel | Superior PFS |
Chemotherapy
- Paclitaxel (Taxol) 90 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
Variant #2, 175 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III (E) | Paclitaxel | Superior PFS |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
Paclitaxel, nanoparticle albumin-bound monotherapy
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Example orders
Variant #1, 100 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | nab-Paclitaxel & Bevacizumab | Inferior PFS |
Note: the details of this regimen are minimal in the manuscript; it is unclear if this is truly given once per week or given in a 3 weeks on, 1 week off schedule.
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV once per week
28-day cycles
Variant #2, 260 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gradishar et al. 2005 | Phase III (E) | Paclitaxel | Superior TTP |
Brufsky et al. 2011 (RIBBON-2) | Phase III (C) | nab-Paclitaxel & Bevacizumab | Inferior PFS |
von Minckwitz et al. 2014 (TANIA) | Phase III (C) | nab-Paclitaxel & Bevacizumab | Inferior PFS |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m2 IV over 30 minutes once on day 1
Supportive medications
- Gradishar et al. 2005: No corticosteroid or antihistamine premedication
21-day cycles
References
- Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. Epub 2005 Sep 19. link to original article contains verified protocol PubMed
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Paclitaxel, nanoparticle albumin-bound & Bevacizumab
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Example orders
Variant #1, 100 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | nab-Paclitaxel | Superior PFS |
Note: the schedule of bevacizumab is inferred, as there was insufficient detail in the description in the manuscript.
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV once per week
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
Variant #2, 260 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III (E) | nab-Paclitaxel | Superior PFS |
von Minckwitz et al. 2014 (TANIA) | Phase III (E) | nab-Paclitaxel | Superior PFS |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- TANIA: von Minckwitz G, Puglisi F, Cortes J, Vrdoljak E, Marschner N, Zielinski C, Villanueva C, Romieu G, Lang I, Ciruelos E, De Laurentiis M, Veyret C, de Ducla S, Freudensprung U, Srock S, Gligorov J. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1269-78. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
- Update: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, González Martín A, de Ducla S, Easton V, von Minckwitz G. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016 Nov;27(11):2046-2052. Epub 2016 Aug 8. link to original article PubMed
Vinorelbine monotherapy
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Variant #1, 25 mg/m2 weekly
Study | Evidence |
---|---|
Gasparini et al. 1994 | Phase II |
Zelek et al. 2001 | Phase II |
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once per week
Continued indefinitely
Variant #2, 30 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Jones et al. 1995 | Phase III (E) | Melphalan | Seems to have superior OS |
Keller et al. 2004 | Phase III (C) | PLD | Seems not superior |
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per week
Continued indefinitely
Variant #3, 30 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III (C) | Vinorelbine & Bevacizumab | Inferior PFS |
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once on day 1
21-day cycles
Variant #4, 30 mg/m2 2 out of 3 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martín et al. 2007 (GEICAM 2000-04) | Phase III (C) | Gemcitabine & Vinorelbine | Inferior PFS |
Robson et al. 2017 (OlympiAD) | Phase III (C) | Olaparib | Inferior PFS |
Patients had confirmed deleterious or suspected deleterious germline BRCA mutation.
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Gasparini G, Caffo O, Barni S, Frontini L, Testolin A, Guglielmi RB, Ambrosini G. Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: a phase II study. J Clin Oncol. 1994 Oct;12(10):2094-101. link to original article PubMed
- Jones S, Winer E, Vogel C, Laufman L, Hutchins L, O'Rourke M, Lembersky B, Budman D, Bigley J, Hohneker J. Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer. J Clin Oncol. 1995 Oct;13(10):2567-74. link to original article contains protocol PubMed
- Zelek L, Barthier S, Riofrio M, Fizazi K, Rixe O, Delord JP, Le Cesne A, Spielmann M. Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma. Cancer. 2001 Nov 1;92(9):2267-72. PubMed
- Keller AM, Mennel RG, Georgoulias VA, Nabholtz JM, Erazo A, Lluch A, Vogel CL, Kaufmann M, von Minckwitz G, Henderson IC, Mellars L, Alland L, Tendler C. Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. J Clin Oncol. 2004 Oct 1;22(19):3893-901. link to original article contains protocol PubMed
- GEICAM 2000-04: Martín M, Ruiz A, Muñoz M, Balil A, García-Mata J, Calvo L, Carrasco E, Mahillo E, Casado A, García-Saenz JA, Escudero MJ, Guillem V, Jara C, Ribelles N, Salas F, Soto C, Morales-Vasquez F, Rodríguez CA, Adrover E, Mel JR; Spanish Breast Cancer Research Group (GEICAM) trial. Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial. Lancet Oncol. 2007 Mar;8(3):219-25. link to original article contains protocol PubMed
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- OlympiAD: Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. link to original article contains verified protocol PubMed
Vinorelbine & Bevacizumab
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Example orders
Variant #1, vinorelbine 25 mg/m2 weekly
Study | Evidence |
---|---|
Burstein et al. 2008 | Phase II |
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
- Bevacizumab (Avastin) 10 mg/kg IV once on day 1
14-day cycles
Variant #2, vinorelbine 30 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III (E) | Vinorelbine | Superior PFS |
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- Burstein HJ, Chen YH, Parker LM, Savoie J, Younger J, Kuter I, Ryan PD, Garber JE, Chen H, Campos SM, Shulman LN, Harris LN, Gelman R, Winer EP. VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin Cancer Res. 2008 Dec 1;14(23):7871-7. link to original article contains verified protocol PubMed
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
Additional resources
- Gail model Breast Cancer Risk Assessment Tool
- Breast cancer BRCA1/BRCA2 genetic testing
- Adjuvant! Online (requires login)
- My Cancer Genome
- PREDICT