Intravesical idarubicin: a dose-finding study.

A total of 12 patients with completely resected, recurrent papillary tumors of the bladder were entered into a dose-finding study using intravesical idarubicin, a new anthracycline agent that has been shown in vitro to be more active than doxorubicin or daunorubicin, its parental compound. Patients were scheduled to receive eight weekly instillations with the following dose levels: 6.5, 12.5, and 20 mg, all of them diluted in 50 ml saline. Each dose level was initially studied in 3 patients. Dose escalation in the individual patients was not allowed so as to avoid undue toxicity and to evaluate the cumulative toxicity induced by each dose level. Overall, 4 patients were withdrawn due to severe local toxicity (chemocystitis) after a median of 2 instillations (range 1-3) and 3 more patients refused to continue treatment due to mild to moderate toxicity after a median of 4 instillations (range 2-4). Both the patients treated with 20 mg idarubicin and 2 of the 6 patients treated with 12.5 mg were withdrawn due to local toxicity. In contrast, no systemic toxicity was encountered at any dose level. We conclude that doses ranging from 6.5 to 12.5 mg and concentrations varying between 0.125 and 0.250 mg/ml are more appropriate for phase II studies, implying repeated instillations. At these doses and concentrations, however, it is unlikely that idarubicin might be more active than doxorubicin or epirubicin, whereas it might be more toxic.