Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA8

Purpose: This phase III study was performed to determine the superiority of doxorubicin (DOX) and virnorelbine (VNB) (arm 1) versus DOX alone (arm 2) in metastatic breast cancer (MBC) for overall survival (OS), time to treatm ent failure (TTF), toxicity, and quality of life (QOL). Patients and Methods: Three hundred three patients were randomized to DOX 5 0 mg/m(2) intravenously (IV) on day 1 and VNB 25 mg/m(2) IV on days 1 and 8 (arm 1) or DOX 70 mg/m(2) IV on day 1 (arm 2). Both regimens were given ev ery 3 weeks until a cumulative DOX dose of 450 mg/m(2). After 16 of the fir st 65 randomized patients experienced febrile neutropenia (FN), the doses w ere reduced to DOX 40 mg/m(2) on day 1 and VNB 20 mg/m(2) on days 1 and 8 v ersus DOX 60 mg/m(2) on day 1. Eligible patients were vinca alkaloid and an thracycline naive. Chemotherapy was first-line or second-line for MBC. Results: Three patients were ineligible. Thus, 300 patients were assessable for toxicity and to determine time to disease progression (TTP), TTF, and OS. Two hundred eighty-nine patients were assessable for response, and 99 r esponders were assessable for response duration (RD). The response rates, Q OL, and median RD, TTP, and TTF were not significantly different between th e arms. Median OS was 13.8 months for arm 1 versus 14.4 months for arm 2 (P = .4). Grade 3 or 4 granulocytopenia was equivalent in both arms but more grade 3/4 neurotoxicity, mild venous toxicity, and FN were seen on arm 1. Conclusion: The survival with DOX and VNB is not superior to BOX alone in M BC. J Clin Oncol 18:2385-2394. (C) 2000 by American Society of Clinical Onc ology.