A comparative study of bisantrene given by two dose schedules in patients with metastatic breast cancer

Schedule dependency of bisantrene was evaluated in refractory metastatic breast cancer. Patients were randomly assigned to receive either a single (S) bolus injection of 300 mg/m² (37 patients) or an injection of 80 mg/m² daily for 5 days (Dx5) (35 patients) every 3-4 weeks after stratification by performance status, dominant disease site, and response to prior doxorubicin therapy. All but one patient had received prior doxorubicin. Partial remission (PR) was achieved by 5 of 35 patients (14%) in the S arm and 7 of 35 patients (20%) in the Dx5 arm (P=NS). There were 4 patients who had primary refractoriness to doxorubicin but responded to bisantrene. The median number of courses was two for both arms. The median time to progression was 5 months for the responders in each arm and 3 and 4 months, respectively, for patients who showed no change in the S and Dx5 arms. Myelosuppression was dose-limiting and greater for the Dx5 arm. Drug fever (34% versus 21% of courses; P=0.02) and myalgia (22% versus 10% of courses; P=0.02) were reported more often in the Dx5 arm; malaise was greater in the S arm. Grade 2-3 nausea and vomiting occurred more often in the S arm (40% versus 10% of courses; P<0.01). Significant hypotension that was not symptomatic occurred in 1 patient in the Dx5 arm. Phlebitis occurred in 3 patients without a central line. One patient who had previously received doxorubicin and mitomycin C developed heart failure, which was controlled with medication. Bisantrene is an effective drug for metastatic breast cancer that has incomplete cross resistance to doxorubicin, and there was no schedule dependency in this study.