Phase I studies of rodorubicin single bolus and daily times five, once every three weeks in patients with advanced solid tumors

Rodorubicin (Cytorhodin S, HLB 817) is a new tetraglycosidic anthracycline with interesting preclinical antitumor activity. We have performed two sequential phase I studies with the drug. In the first study Rodorubicin was administered as a single i.v. administration over 30-360 min, once every 3 weeks. The second study concerned a daily times five i.v. bolus schedule. Thirty patients entered these studies. Regardless of schedule, the dose limiting toxicity appeared to be proteinuria, which was reversible after discontinuation of the drug. Phlebitis was a cumbersome side-effect and it was initially considered to determine the MTD in the once every 3 weeks schedule, but finally it could be prevented by giving the drug as a bolus injection into a rapidly running infusion. Nausea and vomiting were infrequent and mild. Neither myelotoxicity nor alopecia were observed. However, even at low cumulative doses the drug was found to be cardiotoxic using both schedules of administration. Seven out of 12 patients developed grade 1-3 cardiotoxicity, most of them above a cumulative dose of more than 4000 micrograms/m2. These side-effects preclude a dose recommendation for phase II studies with these schedules.