PHASE-II STUDY OF A NEW VINCA ALKALOID DERIVATIVE, S12363, IN ADVANCED BREAST-CANCER

Vinca alkaloids are widely used in the medical treatment of breast can cer. Our study aimed to evaluate the therapeutic activity of a new vin ca alkaloid derivative, S12363 (vinfosiltine), which is 36 and 72 time s more cytotoxic in vitro than vincristine and vinblastine, respective ly. Because phase I studies did not allow a choice of the best treatme nt schedule, a randomization was performed between two schedules with the same dose intensity, that is, 0.3 mg/m(2) given weekly or 0.6 mg/m (2) given every 2 weeks. A total of 16 patients with advanced breast c ancer who had failed a first-line treatment without any vinca alkaloid were entered in the study. Additionally, 6 women received the bimonth ly regimen as first-line treatment of advanced breast cancer. Altogeth er, 17 patients received, prior to vinfosiltine, an anthracycline-base d regimen given either as adjuvant (n = 4) or as first-line palliative treatment (n = 13). All 22 patients were evaluable for both toxicity and response. Neutropenia was the main toxic event (maximal toxicity p er patient) with grade 3 (WHO) toxicity developing in 7/22 patients an d grade 4, in 8/22. Other severe toxicities included leukopenia (n = 9 ), anemia (n = 1), diarrhea (n = 1), constipation (n = 1), and fatigue (n = 1). No patient achieved a complete or partial response. Vinfosil tine does not appear to have significant single-agent activity in adva nced breast cancer at the doses and the schedules used in our study.