The magnitude of benefit from adding taxanes to anthracyclines in the adjuvant settings of breast cancer: discussion of large trials and meta-analyses

Abstract

The taxanes family of chemotherapy, which includes paclitaxel and docetaxel, has been incorporated in the adjuvant breast cancer treatments since 1990s. Sequential and concurrent use of taxanes was investigated with anthracyclines in many adjuvant early breast cancer randomized clinical trials. Results from taxanes trials showed inconsistent benefits. However, several meta-analyses showed significant survival benefit of adding taxanes. In this review article, data were collected and summarized from eleven large randomized trials and three meta-analyses to show and discuss the magnitude of benefit of taxanes-anthracyclines combination compared to anthracyclines only adjuvant regimens in early breast cancer. This article aims at providing the oncologists with a well-organized, inclusive and updated evidence.

Keywords

Breast cancer / adjuvant chemotherapy / taxanes / anthracyclines

References

[1] Early Breast Cancer Trialists' Collaborative Group (EBCTCG).Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials..Lancet2005;365:1687-717

[2] Henderson IC,Demetri GD,Goldstein LJ,Ingle JN,Hayes DF,Fleming G,Duggan DB,Frei E3rd,Wood WC,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 Oncol2003;21:976-83

[3] Martin M,Mackey J,Guastalla JP,Tomiak E,Chap L,Guevin R,Fornander T,Coleman R,Modiano M,Tang SC,Prady C,Walde D,Hugh J,Rupin M,Jacobs P,Riva A.Adjuvant docetaxel for node-positive breast cancer..N Engl J Med2005;352:2302-13

[4] Mackey JR,Pienkowski T,Guastalla JP,Glaspy J,Wardley A,Hainsworth J,Modiano MR,Pinter T,Colwell B,Provencher L,Walde D,Hugh JC,Bassi K,Wilson V,Houé V.Adjuvant docetaxel, doxorubicin, and cyclophosphamide in nodepositive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial..Lancet Oncol2013;14:72-80

[5] Roché H,Spielmann M,Delozier T,Symann M,Soulié P,Viens P,Vindevoghel A,Goudier MJ,Ferrero JM,Genève J.Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial..J Clin Oncol2006;24:5664-71

[6] Nitz U,Huober J,Kates RE,Erber R,Scholz M,Mohrmann S,Augustin D,Weiss E,Kreienberg R,Sattler D,Kiechle M,Wallwiener D,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 Oncol2014;25:1551-7

[7] Mamounas EP,Lembersky B,Sedlacek SM,Wickerham DL,Soran A.Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28..J Clin Oncol2005;23:3686-96

[8] Martín M,Ruiz A,Calvo L,Munárriz B,Crespo C,López García-Asenjo JA,Almenar S,Vera F,Ramos M,Lluch A,Seguí MA,Antón A,Plazaola A,Pelegrí A,Aranda E,Alvarez JV,Sánchez-Rovira P,López-Vega JM.Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer..J Natl Cancer Inst2008;100:805-14

[9] Martín M,Antón A,Ramos M,Aranda I,Grosse R,Barnadas A,Martinez del Prado P,Zaluski J,Muñoz M,Mel JR,Llorca C,Alba E,Li J,Sáez A,Almenar S,Lluch A.Adjuvant docetaxel for high-risk, node-negative breast cancer..N Engl J Med2010;363:2200-10

[10] Goldstein LJ,Sparano JA,Shulman LN,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 Oncol2008;26:4092-9 PMCID:PMC2654376

[11] Ellis P,Johnson L,Wardley A,Verrill M,Yarnold J,Earl H,Twelves C,Bloomfield D,Johnston S,Bartlett JM,Peckitt C,Bliss JM.Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial..Lancet2009;373:1681-92

[12] Burnell M,Chapman JA,Gelmon K,Vandenberg T,Albain KS,Rugo H,O'Brien P.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 Oncol2010;28:77-82 PMCID:PMC2799234

[13] Ferguson T,Vagg R,Nowak AK.Taxanes for adjuvant treatment of early breast cancer..Cochrane Database Syst Rev2007;(4):CD004421

[14] De Laurentiis M,D'Agostino D,Giordano A,Lauria R,Esposito A,Pennacchio R,Montanino A,Bianco AR.Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials..J Clin Oncol2008;26:44-53

[15] Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Peto R,Godwin J,Pan HC,Cutter D,McGale P,Wang YC,Di Leo A,Swain S,Pritchard K.Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials..Lancet2012;379:432-44

[16] Thorn CF,Marsh S,McLeod H,Altman RB.Doxorubicin pathways: pharmacodynamics and adverse effects..Pharmacogenet Genomics2011;21:440-6