PHASE-II TRIAL OF VINORELBINE DOXORUBICIN AS FIRST-LINE THERAPY OF ADVANCED BREAST-CANCER

Purpose: The study investigated the therapeutic effects of a combinati on of Navelbine (vinorelbine or 5'noranhydrovinblastine; Pierre Fabre Medicament, Boulogne, France) and doxorubicin in women who had receive d no prior chemotherapy for locally advanced or metastatic breast canc er. Patients and Methods: Ninety-seven patients with progressive and a ssessable advanced or metastatic breast cancer who had received no pri or chemotherapy except in an adjuvant setting were entered onto the st udy. Eighty-nine patients were assessable for toxicity and response by World Health Organization (WHO) criteria; the other eight patients we re excluded because they did nor meet entry criteria or because of pro tocol violations. Navelbine was administered at 25 mg/m(2) by 30-minut e intravenous (IV) infusion on days 1 and 8, and doxorubicin at 50 mg/ m(2) by slow IV infusion on day 1, with each course repeated at 3-week intervals. patients were treated for a maximum of 11 cycles or until progression or major toxicity. Results: Objective responses were obser ved in 66 of 89 assessable patients (74%; 95% confidence interval, 63% to 85%). There were nineteen (21%) complete responses (CRs) and 47 (5 3%) partial responses (PRs). In addition, 20 patients (22.5%) had stab le disease and three (3.5%) progressed while on treatment. Responses w ere observed at all sites of metastatic disease. Forty-one of 58 patie nts with visceral disease responded (71%) and 25 of 31 with soft tissu e and bone disease experienced an objective response (81%). The median duration of response was 12 months (range, 2.4 to 40.5), and the medi an overall survival was 27.5 months (range, 4 to 46). Neutropenia was dose-limiting, with 36 patients (41%) experiencing grade 3 or 4 toxici ty. Of 727 cycles administered, there were 20 admissions (3%) for trea tment of febrile neutropenia, involving 14 of 89 patients (16%), Treat ment-related cardiotoxicity at grade 2 to 4 was experienced by 10% of patients and necessitated the interruption of treatment in 1.5% of cyc les. Other side effects were uncommon or manageable by conventional me ans. Conclusion: The encouraging response rates and duration achieved with this combination of Navelbine/doxorubicin under the conditions of this study deserve further randomized comparative trials with standar d regimens. (C) 1994 by American Society of Clinical Oncology.