Phase I Clinical Trial of 9,10-Anthracene Dicarboxaldehyde (Bisantrene) Administered in a Five-Day Schedule1

Bisantrene is a substituted anthracene derivative which preclinically demonstrated a spectrum of activity similar to that of doxorubicin but without associated cardiotoxicity. A Phase I evaluation of the drug has been performed using daily i.v. administrations for 5 days. Sixty courses of treatment were administered to 23 patients at doses from 2.5 to 90 mg/sq m/ day. Courses were repeated at 4-week intervals. Dose-limiting toxicities were leukopenia and local cutaneous reactions. The leukopenia was dose related, noncumulative, and of brief du ration. Local reactions occurred in 14 of 37 courses adminis tered at doses >60 mg/sq m and in 3 patients resulted in clinical cellulitis of the infused extremity. Gastrointestinal side effects were mild. No alopecia or cardiotoxicity was observed. Two mixed responses were obtained in patients with hypernephromas. Using a daily schedule for 5 days, approximately 40% more drug can be delivered per course than by singleday i.v. administration. However, with this schedule, local cu taneous reactions may prove additionally dose limiting. Phase II studies of Bisantrene in a daily i.v. schedule for 5 days are planned at a dose of 80 mg/sq m/day to be repeated every 4 weeks.