Efficacy and Safety of Valrubicin for the Treatment of Bacillus Calmette-Guerin Refractory Carcinoma in Situ of the Bladder

PURPOSE: We assess the efficacy and safety of intravesical valrubicin for the treatment of carcinoma in situ in patients with failure or recurrence after bacillus Calmette-Guerin (BCG) and who otherwise would have undergone cystectomy. Total anthracycline recovery in urine samples obtained within 24 hours of valrubicin administration was assessed in a subset of patients. MATERIALS AND METHODS: A total of 90 patients with recurrent carcinoma in situ after failed multiple prior courses of intravesical therapy, including at least 1 course of BCG, participated in this open label, noncomparative study. Each patient received 6 weekly instillations of 800 mg. intravesical valrubicin. Disease evaluations were made at baseline and 3-month intervals following treatment. Evaluations included cystoscopy with biopsy and urine cytology. Toxicity was noted throughout treatment and followup. No evidence of disease recurrence for 6 months or greater was considered a complete response. RESULTS: Of 90 patients 19 (21%) had a complete response, including 7 who remained disease-free at the last evaluation, with a median followup of 30 months. Additionally, 14 patients who did not meet the strict protocol definition of complete response had superficial Ta disease only. Median time to failure and/or last followup for complete responders was greater than 18 months. Recurrence has been noted in 79 patients to date, including only 2 with clinically advanced disease (stage T2). Of these 79 patients 44 (56%, 4 responders and 40 nonresponders) underwent radical cystectomy. Of the 41 patients with known pathological stage 6 (15%) had stage pT3 or greater at cystectomy. Four patients died of bladder cancer during the median followup of 30 months, none of whom was a complete responder or underwent cystectomy following valrubicin. The main side effects of valrubicin therapy were reversible local bladder symptoms. CONCLUSIONS: Valrubicin was effective and well tolerated in patients with carcinoma in situ of the bladder refractory to BCG therapy. Delaying cystectomy while attempting salvage therapy with valrubicin does not pose an undue risk to most patients.