Toxicity of epirubicin and cyclophosphamide (EC) vs. docetaxel (D) followed by EC in the adjuvant (adj) treatment of node positive breast cancer. A multicenter randomized phase III study (GOIM9902)

Abstract

10526 Background: Due to high activity of taxanes (T) and anthracyclines (A) in advanced breast cancer (BC) and to the lack of cross-resistance between them, several adjuvant (adj) trials have been performed to test the efficacy of combination or sequential schedules of T and A adjuvant. In most of the sequential trials A followed T. The sequence T->A was proven active in metastatic BC, but no data are available in the adj setting. This multicenter randomized phase III study was designed to evaluate the efficacy of the sequence T->A vs an A containing regimen Methods: Pts with pT1–3 pN1 M0 (UICC1997) BC, age 18–70, PS(ECOG) 0–1, normal cardiac function, adequate bone marrow, hepatic and renal function were eligible for the study. Pts were stratified according to institution, age (≤ 50 vs > 50), hormonal receptor status and number of involved nodes (≤ 3, 4–9, ≥ 10) and were randomized to receive either 4 cycles of EC (Epirubicin 120 mg/m2 + Cyclophosphamide 600 mg/m2 on day 1 q21) in arm A or 4 cycles of D (100 mg/m2 on day 1 q21) followed by 4 cycles of EC in arm B. Primary endpoint was DFS. Secondary endpoints OS and toxicity. Results: Between april 1999 and october 2005, 750 pts were enrolled (374 in arm A and 376 in arm B) in 25 Italian institutions. Pts characteristics are as follows: Arm A: age ≤ 50 yrs 185/374; ≤ 3 nodes 182/374, 4–9 nodes 129/374, ≥ 10 nodes 63/374; positive HR 287/374 Arm B: age ≤ 50 yrs 197/376; ≤ 3 nodes 184/376, 4–9 nodes 131/376, ≥ 10 nodes 61/376; positive HR 289/376 Toxicity data (Arm A vs Arm B) of the first 495(241/254) pts are the following: Neutropenia G3 (29% vs 21.3%), neutropenia G4 (32.7% vs 48.8%), febrile neutropenia G3–4 (3.7% vs 9.5%), thrombocytopenia G3–4 (3.3% vs 1.6%), anemia G3 (0% vs 2.4%), N/V G3–4 (6.2% vs 3.1%), mucositis G3–4 (3.7% vs 3.9%), diarrhea G3–4 (0.4% vs 2.8%), peripheral neuropathy G1–3 (0% vs 9.9%), hypersensitivity reactions G3–4 (0% vs 4.3%), cardiac toxicity G3 (0.4% vs 0%) Conclusions: Treatment was generally well tollerated in both arms with a higher incidence of neutropenia, usually short lasting, in arm B. The use of prophylactic G-CSF in those patients experiencing neutropenia G3–4 may be advisable. There were no significant differences in cardiac toxicity. No significant financial relationships to disclose.