VINCRISTINE WITH HIGH-DOSE ETOPOSIDE IN ADVANCED BREAST-CANCER - A PHASE-II TRIAL OF THE PIEDMONT-ONCOLOGY-ASSOCIATION

Vincristine (VCR) and etoposide (VP-16) have been shown to be synergis tic in a murine model, and this combination was studied in a phase II trial. Eligibility required measurable disease, a performance status o f 0-2, a life expectancy of greater than or equal to 2 months, an inte rval of at least 3 weeks since the receipt of previous radiation thera py or chemotherapy and recovery from related toxicity, no prior treatm ent with VCR or VP-16, and no more than two prior chemotherapy regimen s (only one for treatment of metastatic disease). Treatment consisted of 0.5 mg i.v. (bolus) VCR followed by 200 mg/m(2) VP-16 given over 2 h. Both drugs were given daily for 3 consecutive days every 3 weeks (t otal dose: VCR, 1.5 mg; VP-16, 600 mg/m(2)). A total of 18 patients wi th metastatic breast cancer were accured; 14 had adjuvant chemotherapy and 8 had chemotherapy for advanced disease. As judged by Internation al Union Against Cancer (UICC) criteria, one complete response (CR) an d three partial responses (PR) were obtained, for a CR+PR rate of 22% (95% confidence interval, 6%-48%). All responders had soft-tissue invo lvement only. Six patients had stable disease and 8 showed progression . The median time to treatment failure was 3.5 months, and the median survival from study entry was 8.3 months. The major toxicity was myelo suppression, with 9 patients (50%) experiencing a total WBC of < 1,000 /mm(3). Grade 2-3 neurologic toxicity was noted in 6 patients (33%) an d grade 3 nausea and vomiting was Doted in 5 (28%). The combination of VCR and VP-16 is active in advanced breast cancer but is not convinci ngly superior to either of these agents used alone.