Intravesical combination chemotherapy with mitomycin C and doxorubicin for superficial bladder cancer: a randomized trial of maintenance versus no maintenance following a complete response
From October 1983 to September 1985, 84 patients with superficial bladder tumor (Ta, Tl, Tis) were treated with sequential instillation of mitomycin C (MMC) and adriamycin (ADM). Doses of 20 mg MMC on day 1 and 40 mg ADM on day 2 were instilled into the bladder and retained for at least 2 h; this was repeated once a week for 5 consecutive weeks. Patients who achieved complete response (CR), were randomized and underwent prophylactic treatment taking the form of either intermittent instillation of MMC or daily oral administration of 5-fluorouracil. Of 79 evaluable patients, 72 (91%) had received prior treatment for superficial bladder tumors, 69 (87%) had high-grade tumors, and 18 (23%) had non-papillary Tis. The overall response rate was 68%, made up of CR in 43 patients (54%) and partial response (PR) in 11 (14%). Patients with either five or more tumors or tumors larger than 1 cm showed a significantly lower response rate than those with fewer than five tumors and tumors smaller than 1 cm, respectively. There was no correlation between tumor growth pattern, tumor grade and response rate, though non-papillary Tis appeared to respond better than papillary tumors. A history of prior instillation therapy or of toxicity to this treatment had no significant influence on the response rate. Although no systemic toxicity was observed, 62 patients (74%) experienced cystitis and the treatment had to be discontinued within 4 weeks in 13 of 33 cases with severe symptoms. The preliminary conclusion of prophylactic treatment was that intermittent instillation of MMC was superior to 5-FU medication in reducing the recurrence rate for at least 2 years after the treatment.