Top

Published in:

01-01-2016 | Clinical trial

5-Fluorouracil, epirubicin and cyclophosphamide versus epirubicin and paclitaxel in node-positive early breast cancer: a phase-III randomized GONO-MIG5 trial

Authors: Lucia Del Mastro, Alessia Levaggi, Andrea Michelotti, Giovanna Cavazzini, Francesca Adami, Tiziana Scotto, Margherita Piras, Saverio Danese, Ornella Garrone, Antonio Durando, Valeria Accortanzo, Claudia Bighin, Loredana Miglietta, Simona Pastorino, Paolo Pronzato, Federico Castiglione, Elisabetta Landucci, PierFranco Conte, Paolo Bruzzi

Published in: Breast Cancer Research and Treatment | Issue 1/2016

Abstract

The study was designed to compare an anthracycline-containing regimen to a regimen combining both anthracycline and paclitaxel as adjuvant therapy for high-risk breast cancer patients. In this multicenter, randomized phase-III trial, node-positive early breast cancer patients were randomly assigned to receive either 6 cycles of FEC (5-fluorouracil 600 mg/m², epirubicin 60 mg/m² and cyclophosphamide 600 mg/m², day 1, every 3 weeks) or 4 cycles of EP (epirubicin 90 mg/m² and paclitaxel 175 mg/m², day 1, every 3 weeks). The primary endpoint was overall survival (OS). Secondary endpoints included toxicity and event-free survival (EFS). From 1996 to 2001, 1055 patients were enrolled. At a median follow-up of 12.8 years, 335 deaths had been recorded. The 10-year OS was 73 % (95 % CI 69–77) in the FEC arm and 74 % (95 % CI 70–78) in the EP arm (p = 0.405). The 10-year EFS was 51 % (95 % CI 45–56) in the FEC arm and 49 % (95 % CI 44–55) in the EP arm (p = 0.572). No difference in the hazard of death was observed (HR for EP 0.85, 95 % CI 0.68–1.06, p = 0.15). Patients treated with FEC experienced more frequently nausea and vomiting, stomatitis, and leukopenia as compared to patients treated with EP. Toxicities which occurred more frequently with EP were anemia, fever, myalgias, and neurotoxicity. Our study failed to demonstrate a superiority of an adjuvant treatment with four EP as compared to six FEC in node-positive breast cancer patients.

Available only for authorised users

Holmes FA, Walters RS, Theriault R, Forman AD, Newton LK, Raber MN, Buzdar AU, Frye DK, Hortobagyi GN (1991) Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst 83:1797–1805PubMedCrossRef

Gianni L, Munzone E, Capri G, Villani F, Spreafico C, Tarenzi E, Fulfaro F, Caraceni A, Martini C, Laffranchi A et al (1995) Paclitaxel in metastatic breast cancer: a trial of two doses by a 3-hour infusion in patients with disease recurrence after prior therapy with anthracyclines. J Natl Cancer Inst 87:1169–1175PubMedCrossRef

Gianni L, Munzone E, Capri G, Fulfaro F, Tarenzi E, Villani F, Spreafico C, Laffranchi A, Caraceni A, Martini C et al (1995) 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 13:2688–2699PubMed

Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214PubMedCrossRef

French Adjuvant Study Group (2001) 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 19:602–611

Van der Hage JA, Van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L (2001) Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer Trial 10902. J Clin Oncol 19:4224–4237PubMed

Mouridsen HT, Andersen M, Dombernowsky P et al. (1999) Adjuvant anthracycline in breast cancer: improved outcome in premenopausal patients following substitution of methotrexate in the CMF combination with epirubicin. Proc Am Soc Clin Oncol 18(68a); (abstr 254)

Henderson IC, Berry DA, Dimetri 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 (2003) 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 21:976–983PubMedCrossRef

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 (2009) Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trail in Operable breast cancer. J Clin Oncol 27:2474–2481PubMedCrossRef

10.

Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N (2005) Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol 23:3686–3696PubMedCrossRef

11.

Martin M, Rodriguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Munárriz B, Rodríguez CA, Crespo C, de Alava E, López García-Asenjo JA, Guitián MD, Almenar S, González-Palacios JF, Vera F, Palacios J, Ramos M, Gracia Marco JM, Lluch A, Alvarez I, Seguí MA, Mayordomo JI, Antón A, Baena JM, Plazaola A, Modolell A, Pelegrí A, Mel JR, Aranda E, Adrover E, Alvarez JV, García Puche JL, Sánchez-Rovira P, Gonzalez S, López-Vega JM, GEICAM 9906 Study Investigators (2008) Randomized phase 3 trial of Fluorouracil, Epirubicin, and Cuclophosphamide alone or followed by Paclitaxel for early breast cancer. J Natl Cancer Inst 100:805–814PubMedCrossRef

12.

Fountzilas G, Skarlos D, Dafni U, Gogas H, Briasoulis E, Pectasides D, Papadimitriou C, Markopoulos C, Polychronis A, Kalofonos HP, Siafaka V, Kosmidis P, Timotheadou E, Tsavdaridis D, Bafaloukos D, Papakostas P, Razis E, Makrantonakis P, Aravantinos G, Christodoulou C, Dimopoulos AM (2005) Post-operative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 16:1762–1771PubMedCrossRef

13.

Jm Albert, Buzdar AU, Guzman R, Allen PK, Strom EA, Perkins GH, Woodward WA, Hoffman KE, Tereffe W, Hunt KK, Buchholz TA, Oh JL (2011) Prospective randomized trial of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus paclitaxel and FAC (TFAC) in patients with operable breast cancer: impact of taxane chemotherapy on locoregional control. Breast Cancer Res Treat 128:421–427CrossRef

14.

Burnell M, Levine MN, Chapman JAW, Bramwell V, Gelmon K, Walley B, Vandenberg T, Chalchal H, Albain KS, Perez EA, Rugo H, Pritchard K, O’Brien P, Shepherd LE (2010) 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-nagative breast cancer. J Clin Oncol 28:77–82PubMedPubMedCentralCrossRef

15.

Martin M, Rodriguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Santaballa A, Rodríguez CA, Crespo C, Abad M, Domínguez S, Florián J, Llorca C, Méndez M, Godes M, Cubedo R, Murias A, Batista N, García MJ, Caballero R, de Alava E (2010) Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer. Breast Cancer Res Treat 123:149–157PubMedCrossRef

16.

Early Breast Cancer Trialists’ Cooperative Group (EBCTCG), Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K (2012) Comparison between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379:432–444CrossRef

17.

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 (2008) Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with Trastuzumab for all HER-2 overespressors and random assignment to trastuzumab or not in HER-2 non-overespressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol 26:1642–1649PubMedCrossRef

18.

Sparano JA, Zhao F, Martino S, Ligibel JA, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE (2015) Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer. J Clin Oncol 33:2353–2360PubMedCrossRef

19.

Sparano JA, O’Neill A, Gray RJ et al. (2012) 10-year update of E2197: phase III doxorubicin/docetaxel (AT) versus doxorubicin/cyclophosphamide (AC) adjuvant treatment of LN + and high-risk LN- breast cancer and the comparison of the prognostic utility of the 21-gene recurrence score (RS) with clinicopathologic features. J Clin Oncol (suppl; abstr 1021)

20.

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 (2010) Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 362:2053–2065PubMedPubMedCentralCrossRef

21.

Bianco AR, Del Mastro L, Gallo C, Perrone F, Matano E, Pagliarulo C, De Placido S (1991) Prognostic role of amenorrhea induced by adjuvant chemotherapy in premenopausal patients with early breast cancer. Br J Cancer 63:799–803PubMedPubMedCentralCrossRef

22.

Goldhirsh A, Gelber RD, Castiglione M (1990) The magnitude of endocrine effects of adjuvant chemotherapy for premenopausal breast cancer patients. Ann Oncol 1:183–188

Title: 5-Fluorouracil, epirubicin and cyclophosphamide versus epirubicin and paclitaxel in node-positive early breast cancer: a phase-III randomized GONO-MIG5 trial
Authors: Lucia Del Mastro
Alessia Levaggi
Andrea Michelotti
Giovanna Cavazzini
Francesca Adami
Tiziana Scotto
Margherita Piras
Saverio Danese
Ornella Garrone
Antonio Durando
Valeria Accortanzo
Claudia Bighin
Loredana Miglietta
Simona Pastorino
Paolo Pronzato
Federico Castiglione
Elisabetta Landucci
PierFranco Conte
Paolo Bruzzi
Publication date: 01-01-2016
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2016
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-015-3655-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2016

Factors associated with radiation therapy incompletion for patients with early-stage breast cancer

Survivin contributes to DNA repair by homologous recombination in breast cancer cells

Clinical utility of reverse phase protein array for molecular classification of breast cancer

Impact of guideline-based use of uPA/PAI-1 on patient outcome in intermediate-risk early breast cancer

A randomized, double-blind, phase II, exploratory trial evaluating the palliative benefit of either continuing pamidronate or switching to zoledronic acid in patients with high-risk bone metastases from breast cancer

The therapy with negative pressure as a valid device to treat chronic breast infections

Keynote webinar | Spotlight on antibody–drug conjugates in cancer