Evaluation of adriamycin and dibromodulcitol in metastatic breast carcinoma

A phase 1 to 2 evaluation of a combination of adriamycin (ADR) and dibromodulcitol (DBD) was performed in patients with progressive, metastatic breast carcinoma. All but one patient had been treated previously with chemotherapy. ADR was given on Day 1 or Days 1 and 8, and DBD was given on Days 1 to 10 of each 21- to 28-day treatment cycle. Side effects were evaluable in 54 patients, and 50 patients were evaluable for therapeutic response. The dose-limiting toxicities were leukopenia and thrombocytopenia. The severity of both toxicities increased as both the ADR and DBD doses increased; however, the effect of increases in DBD dose was much more profound. The mean white blood cell count and platelet nadirs occurred, respectively, on Days 15.3 and 15.9; both nadirs were delayed for 0.6 day by each 30-mg/sq m/day increase in the DBD dose and delayed for 1.7 to 3.9 days using the Day 1, 8 rather than the Day 1 ADR schedule Recovery of the peripheral counts by Day 29 was prolonged by the Day 1, 8 ADR schedule and by increasing the DBD dose. A tolerable dose schedule for previously treated patients was considered to be ADR, 40 mg/sq m on Day 1, and DBD, 135 mg/sq m on Days 1 to 10 repeated every 28 days. Responses were observed in 46% (23 of 50) of the patients. There were 1 complete remission, 19 partial remissions, and 3 improvements. Thirteen patients showed no change and 14 developed progressive disease. There were responses in 13 of 37 (36%) with visceral dominant disease as compared to 7 of 8 (87%) with osseous and 3 of 5 (60%) with soft tissue-dominant disease. There were 22 of 48 (46%) responses in patients previously exposed to alkylating agent therapy. Twnety-two patients had responded and 19 had failed to respond to prior alkylating agent-containing regimens; the response rates to DBD in these groups were respectively, 45 and 42%. The median time to remission was 29 days. The median time to therapeutic failure was 5.1 months for responders, 2.3 months for patients with no change, and 29 days for progressors. The combination of ADR and DBD appears to be an active and well-tolerated program in patients with previously treated metastatic breast carcinoma.