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 (D x 5) (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 D X 5 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 D X 5 arms. Myelo-suppression was dose-limiting and greater for the D X 5 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 D X 5 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 less than 0.01). Significant
hypotension that was not symptomatic occurred in 1 patient in the D X 5 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.