FIRST-LINE VINORELBINE-MITOXANTRONE COMBINATION IN METASTATIC BREAST-CANCER PATIENTS RELAPSING AFTER AN ADJUVANT ANTHRACYCLINE REGIMEN - RESULTS OF A PHASE-II STUDY

Purpose: Previous studies demonstrated that doxorubicin and vinorelbin e combinations in first-line chemotherapy are highly active in metasta tic breast cancer. Mitoxantrone is an anthracenedione with low cardiot oxicity, and seems to be effective when combined with vinorelbine afte r prior exposure to anthracyclines. Patients and Methods: Seventy-two patients with metastatic breast cancer were included in a phase II stu dy. All patients had previously received one anthracycline-containing regimen (doxorubicin or epirubicin) in an adjuvant setting. Vinorelbin e was administered at 25 mg/m(2) in a 20-min intravenous (i.v.) infusi on, days 1 and 8. Mitoxantrone was given at 10 mg/m(2) (66 patients) o r 12 mg/m(2) (6 patients) in a slow i.v. infusion on day 1. Courses we re repeated every 3 weeks. Results: Sixty-five patients were evaluable for response; the objective response rate was 49% (95% CI: 37-63%), i ncluding four complete and 28 partial responses, with a median duratio n of response of 7 months (range 2.3-27). Median overall survival was 19 months (range 2-48). Grade 3-4 granulocytopenia was observed in 46% of patients. There were 12 admissions (3% of cycles), involving 17% o f patients for febrile neutropenia. Seven patients (10%) experienced g rade 3 or 4 cardiotoxicity, and 1 patient died of cardiac heart failur e. Other side effects were rare and mild. Conclusions: The vinorelbine and mitoxantrone combination is an active regimen with low toxic comp lications when cumulative doses of mitoxantrone are limited to 70 mg/m (2). The results in this phase II study make it worthwhile including t his regimen in a phase III study for patients who have previously rece ived an anthracycline-containing regimen.