INTRAVESICAL IDARUBICIN - A DOSE-FINDING STUDY

A total of 12 patients with completely resected, recurrent papillary t umors of the bladder were entered into a dose-finding study using intr avesical 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 instillatio ns with the following dose levels: 6.5, 12.5, and 20 mg, all of them d iluted in 50 ml saline. Each dose level was initially studied in 3 pat ients. Dose escalation in the individual patients was not allowed so a s to avoid undue toxicity and to evaluate the cumulative toxicity indu ced by each dose level. Overall, 4 patients were withdrawn due to seve re local toxicity (chemocystitis) after a median of 2 instillations (r ange 1-3) and 3 more patients refused to continue treatment due to mil d to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 Both the patients treated with 20 mg idarubicin and 2 of the 6 patient s treated with 12.5 mg were withdrawn due to local toxicity. In contra st, no systemic toxicity was encountered at any dose level. We conclud e that doses ranging from 6.5 to 12.5 mg and concentrations varying be tween 0.125 and 0.250 mg/ml are more appropriate for phase II studies, implying repeated instillations. At these doses and concentrations, h owever, it is unlikely that idarubicin might be more active than doxor ubicin or epirubicin, whereas it might be more toxic.