Fluorouracil, Epirubicin, and Cyclophosphamide Alone or Followed by Paclitaxel for Early Breast Cancer

Summary

The efficacy of adjuvant chemotherapy is limited in patients with a high risk of recurrence. Also, for axillary positive node patients, optimum chemotherapy regimens are still under discussion. Some previous studies suggest that, in the subset of node-positive patients, treatments based on sequential administration of anthracyclines and taxanes are more efficient. Paclitaxel dose-dense (weekly) administration renders an improved therapeutic index (activity/toxicity). The study is designed to compare 6 courses of FEC scheme (600/90/600), a combination of proven efficacy in node positive breast cancer patients, versus 4 FEC courses followed by 8 weekly paclitaxel administrations (100mg/m2). The study hypothesis is that 5-year disease-free survival in the control arm will be 60%. The investigators expect to increase this by 8% with the experimental treatment. With an alpha error of 0.05, 80% power, and a post-randomization estimated drop-out rate of 10%, 1250 patients are needed, 625 per arm.

Timeline

Start

1999-11

Primary completion

2005-12

Completion

2007-12

Publications

• Results Martin M, Rodriguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Santaballa A, Rodriguez CA, Crespo C, Abad M, Dominguez S, Florian J, Llorca C, Mendez M, Godes M, Cubedo R, Murias A, Batista N, Garcia MJ, Caballero R, de Alava E. Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer. Breast Cancer Res Treat. 2010 Aug;123(1):149-57. doi: 10.1007/s10549-009-0663-z.
• Results Ebbert MT, Bastien RR, Boucher KM, Martin M, Carrasco E, Caballero R, Stijleman IJ, Bernard PS, Facelli JC. Characterization of uncertainty in the classification of multivariate assays: application to PAM50 centroid-based genomic predictors for breast cancer treatment plans. J Clin Bioinforma. 2011 Dec 23;1:37. doi: 10.1186/2043-9113-1-37.
• Results de la Haba-Rodriguez J, Rodriguez-Lescure A, Ruiz A, Alba E, Calvo L, Carrasco E, Escudero MJ, Martin M. Regional and seasonal influence in patient's toxicity to adjuvant chemotherapy for early breast cancer. Breast Cancer Res Treat. 2011 Jan;125(1):273-8. doi: 10.1007/s10549-010-1136-0. Epub 2010 Aug 28.
• Results Bastien RR, Rodriguez-Lescure A, Ebbert MT, Prat A, Munarriz B, Rowe L, Miller P, Ruiz-Borrego M, Anderson D, Lyons B, Alvarez I, Dowell T, Wall D, Segui MA, Barley L, Boucher KM, Alba E, Pappas L, Davis CA, Aranda I, Fauron C, Stijleman IJ, Palacios J, Anton A, Carrasco E, Caballero R, Ellis MJ, Nielsen TO, Perou CM, Astill M, Bernard PS, Martin M. PAM50 breast cancer subtyping by RT-qPCR and concordance with standard clinical molecular markers. BMC Med Genomics. 2012 Oct 4;5:44. doi: 10.1186/1755-8794-5-44.
• Results Pajares B, Pollan M, Martin M, Mackey JR, Lluch A, Gavila J, Vogel C, Ruiz-Borrego M, Calvo L, Pienkowski T, Rodriguez-Lescure A, Segui MA, Tredan O, Anton A, Ramos M, Camara Mdel C, Rodriguez-Martin C, Carrasco E, Alba E. Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis. Breast Cancer Res. 2013 Nov 6;15(6):R105. doi: 10.1186/bcr3572.
• Results Martin M, Prat A, Rodriguez-Lescure A, Caballero R, Ebbert MT, Munarriz B, Ruiz-Borrego M, Bastien RR, Crespo C, Davis C, Rodriguez CA, Lopez-Vega JM, Furio V, Garcia AM, Casas M, Ellis MJ, Berry DA, Pitcher BN, Harris L, Ruiz A, Winer E, Hudis C, Stijleman IJ, Tuck DP, Carrasco E, Perou CM, Bernard PS. PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer. Breast Cancer Res Treat. 2013 Apr;138(2):457-66. doi: 10.1007/s10549-013-2416-2. Epub 2013 Feb 20.
• Results Prat A, Cheang MC, Martin M, Parker JS, Carrasco E, Caballero R, Tyldesley S, Gelmon K, Bernard PS, Nielsen TO, Perou CM. Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer. J Clin Oncol. 2013 Jan 10;31(2):203-9. doi: 10.1200/JCO.2012.43.4134. Epub 2012 Dec 10.
• Results Martin M, Brase JC, Calvo L, Krappmann K, Ruiz-Borrego M, Fisch K, Ruiz A, Weber KE, Munarriz B, Petry C, Rodriguez CA, Kronenwett R, Crespo C, Alba E, Carrasco E, Casas M, Caballero R, Rodriguez-Lescure A. Clinical validation of the EndoPredict test in node-positive, chemotherapy-treated ER+/HER2- breast cancer patients: results from the GEICAM 9906 trial. Breast Cancer Res. 2014 Apr 12;16(2):R38. doi: 10.1186/bcr3642.
• Results Cheang MC, Martin M, Nielsen TO, Prat A, Voduc D, Rodriguez-Lescure A, Ruiz A, Chia S, Shepherd L, Ruiz-Borrego M, Calvo L, Alba E, Carrasco E, Caballero R, Tu D, Pritchard KI, Levine MN, Bramwell VH, Parker J, Bernard PS, Ellis MJ, Perou CM, Di Leo A, Carey LA. Defining breast cancer intrinsic subtypes by quantitative receptor expression. Oncologist. 2015 May;20(5):474-82. doi: 10.1634/theoncologist.2014-0372. Epub 2015 Apr 23.
• Results Martin M, Brase JC, Ruiz A, Prat A, Kronenwett R, Calvo L, Petry C, Bernard PS, Ruiz-Borrego M, Weber KE, Rodriguez CA, Alvarez IM, Segui MA, Perou CM, Casas M, Carrasco E, Caballero R, Rodriguez-Lescure A. Prognostic ability of EndoPredict compared to research-based versions of the PAM50 risk of recurrence (ROR) scores in node-positive, estrogen receptor-positive, and HER2-negative breast cancer. A GEICAM/9906 sub-study. Breast Cancer Res Treat. 2016 Feb;156(1):81-9. doi: 10.1007/s10549-016-3725-z. Epub 2016 Feb 24.
• Results Templeton AJ, Rodriguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Santaballa A, Rodriguez CA, Crespo C, Ramos M, Gracia-Marco JM, Lluch A, Alvarez I, Casas MI, Sanchez-Arago M, Caballero R, Carrasco E, Amir E, Martin M, Ocana A; GEICAM 9906 Study Investigators. Prognostic role for the derived neutrophil-to-lymphocyte ratio in early breast cancer: a GEICAM/9906 substudy. Clin Transl Oncol. 2018 Dec;20(12):1548-1556. doi: 10.1007/s12094-018-1885-5. Epub 2018 May 15.
• Results Sestak I, Martin M, Dubsky P, Kronenwett R, Rojo F, Cuzick J, Filipits M, Ruiz A, Gradishar W, Soliman H, Schwartzberg L, Buus R, Hlauschek D, Rodriguez-Lescure A, Gnant M. Prediction of chemotherapy benefit by EndoPredict in patients with breast cancer who received adjuvant endocrine therapy plus chemotherapy or endocrine therapy alone. Breast Cancer Res Treat. 2019 Jul;176(2):377-386. doi: 10.1007/s10549-019-05226-8. Epub 2019 Apr 30.
• Results Camp NJ, Madsen MJ, Herranz J, Rodriguez-Lescure A, Ruiz A, Martin M, Bernard PS. Re-interpretation of PAM50 gene expression as quantitative tumor dimensions shows utility for clinical trials: application to prognosis and response to paclitaxel in breast cancer. Breast Cancer Res Treat. 2019 May;175(1):129-139. doi: 10.1007/s10549-018-05097-5. Epub 2019 Jan 23.
• Results Ethier JL, Ocana A, Rodriguez Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Santaballa A, Rodriguez CA, Crespo C, Ramos M, Gracia Marco J, Lluch A, Alvarez I, Casas M, Sanchez-Arago M, Carrasco E, Caballero R, Amir E, Martin M. Outcomes of single versus double hormone receptor-positive breast cancer. A GEICAM/9906 sub-study. Eur J Cancer. 2018 May;94:199-205. doi: 10.1016/j.ejca.2018.02.018. Epub 2018 Mar 21.
• Martin M, Carrasco E, Rodriguez-Lescure A, Andres R, Servitja S, Anton A, Ruiz-Borrego M, Bermejo B, Guerrero A, Ramos M, Santaballa A, Munoz M, Cruz J, Lopez-Tarruella S, Chacon JI, Alvarez I, Martinez P, Miralles JJ, Polonio O, Jara C, Aguiar-Bujanda D. Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Alamo IV registry. Breast Cancer Res Treat. 2023 Sep;201(2):151-159. doi: 10.1007/s10549-023-07002-1. Epub 2023 Jun 20.

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