Cyclophosphamide, epirubicin, and 5-fluorouracil versus epirubicin plus paclitaxel in node-positive early breast cancer patients: A randomized, phase III study of Gruppo Oncologico Nord Ovest-Mammella Intergruppo Group

Abstract

516 Background: This trial is aimed at comparing the efficacy and tolerability of 2 regimens of adjuvant therapy for patients (pts) with node-positive breast cancer. Methods: Women with operable, N+ breast cancer and less than 10 involved axillary nodes were eligible. Therapy was as follows: Arm 1 (CEF): cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2 and 5-fluorouracil 600 mg/m2 given every 3 weeks for 6 cycles; Arm 2 (ET): epirubicin 90 mg/m2, paclitaxel 175 mg/m2 3-hour infusion given every 3 weeks for 4 cycles. Tamoxifen (20 mg/die) was given to all pts with ER and/or PgR positive tumor. Primary endpoint was overall survival (OS) and secondary endpoints were event free survival (EFS) and tolerability. The study was designed to detect a hazard ratio of 0.80, assuming an alpha error of 0.05 (two sided) and a power of 0.80. This required 500 pts per arm. Results: From Nov 1996 to Jan 2001, 1,055 pts were randomized: 520 pts received CEF and 535 ET regimens. Main pts characteristics were age <50 years (35% and 42% in arm 1 and 2, respectively); N+1–3 (68% and 69%); ER and PgR negative status (24% and 19%). Pts treated with CEF experienced more frequently nausea/vomiting (85% in arm 1 and 76% in arm 2, p=0.0001), mucositis (46% vs 37%, p=0.003) and leukopenia (52% vs 40%, p=0.0002). Toxicities occurring more frequently in ET arm were anemia (17% vs 25% in arm 1 and 2, respectively, p=0.006); fever (7% vs 15%, p=0.0001); myalgia (1% vs 19%, p=0.0001); neurotoxicity (6% vs 38%, p <0.0001) and allergic reaction (1% vs 5%, p=0.03). Among 412 premenopausal pts, chemotherapy-induced amenorrhea occurred in 51% of pts treated with CEF and in 45% of pts treated with ET (p=0.16). The median follow-up in surviving pts was 8.2 years. At Dec 2007, 223 deaths and 344 events were recorded. The 5-year EFS was 71% and 70% in arm 1 and 2 respectively; 10-year EFS was 46% in both arms. The 5-year OS was 89% and 88% in arm 1 and 2, respectively; the 10-year OS was 72% (95% CI: 66–78) and 76% (95% CI: 71–80) (p=0.8). Conclusions: CEF for 6 cycles and ET for 4 cycles are associated with a different toxicity profile. At 5- and 10 years, no significant difference in OS and EFS was observed between CEF and ET regimens. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb