A prospective randomised trial of radiation with or without oral and intravesical misonidazole for bladder cancer.

Patients with T2 grade 3 and T3 bladder cancer were randomised to be treated with radiation alone (NO MISO) or with radiation and misonidazole (PLUS MISO). Patients in both groups initially received 40 Gy in 2 Gy fractions (5/week). Patients in the NO MISO arm received a further 20 Gy in 2 Gy fractions (5/week). Patients in the PLUS MISO arm received a further 12 Gy in 6 Gy fractions (1/week). MISO was administered orally (3.0 g m-2) and intravesically (1.0 g in 35 ml of solvent) 4 h and 2 h respectively prior to each fraction of 6 Gy. Fifty-eight patients were randomized of whom 53 are evaluable. There is a minimum follow-up of 5 years in the surviving patients. In the NO MISO and PLUS MISO arms, the complete response rate at cystoscopy at 6 months was 63% and 69%, the 5-year survival rate was 41% and 48% and the 5-year local control rate with bladder preservation was 46% and 36% respectively (censored for death from metastases while locally clear). These differences are not statistically significant. Two patients had grade 3 RTOG late bowel complications. Both patients were in the PLUS MISO arm, had undergone salvage cystectomy and subsequently required colostomies for bowel obstruction for a 5-year late complication rate (RTOG grade 3) of 9%. In addition, two patients in the PLUS MISO arm developed wound sepsis post cystectomy. We were not able to demonstrate improved results from the use of oral and intravesical MISO in this study. The number of patients entered are relatively low and large differences would have been required to be detected with a power of 0.80. The use of an unconventional radiation fractionation schedule may have resulted in increased bowel morbidity in patients in the PLUS MISO arm who subsequently underwent cystectomy.

RCT Entities:   Population Interventions Outcomes