Phase I and pharmacology study of intravesical mitoxantrone for recurrent superficial bladder tumors.

A phase 1 study of intravesical mitoxantrone was done in patients with superficial bladder tumors recurrent after previous intravesical therapy. Mitoxantrone (5 to 10.5 mg.) was instilled in the bladder via catheter and was left in situ for 2 hours. Each patient received 6 treatments at 1-week intervals. Pharmacology studies were conducted in a subset of consenting patients. Dysuria, urinary frequency and hematuria were dose-limiting at 10 to 10.5 mg., the dose recommended for our phase 2 studies. One patient treated with 7.5 mg. mitoxantrone had bladder contracture after severe bladder injury caused by the drug. The interval free of recurrence increased in 5 of 8 patients treated with 10 to 10.5 mg. mitoxantrone and in 6 of 19 treated at lower dose levels. One patient who had residual evaluable tumor in the bladder at treatment experienced a complete remission for 16 months. Only 1 of 18 patients who underwent pharmacology studies had any mitoxantrone detectable in the blood after intravesical administration. This patient had severe irritative symptoms at treatment. No systemic toxicity was noted in any patient. Of the mitoxantrone instilled into the bladder 33 to 100% (mean 75%) was recovered in the specimen voided at the end of treatment. In summary, intravesical mitoxantrone is reasonably well tolerated and should be studied further at a dose of 10 mg. per week for 6 weeks. Caution should be exercised, since bladder contracture was seen in 1 patient. Systemic absorption and toxicity are negligible.