Effect of misonidazole dose on survival in patients with stage IIIB-IVA squamous cell carcinoma of the uterine cervix: an RTOG randomized trial.

Between August 1980 and November 1984, 120 patients with FIGO Stage IIIB or IVA squamous cell carcinoma of the uterine cervix were randomized to receive radiation therapy (RT) (46 Gy pelvis + 10 Gy parametrial boost) followed by intracavitary or external boost to the primary +/- misonidazole (MISO) (400 mg/M2 2-4 hours prior to RT daily, maximum 12 gm/M2). The median at 24-28 hr misonidazole plasma level was 20 micrograms/ml 2-6 hr and 3.5 micrograms/ml. Approximately 60% of the patients on RT + MISO received 100% of expected total Misonidazole dose; peripheral neurologic toxicity was reported for nine patients receiving misonidazole (8 with mild and 1 with moderate paresthesia or pain). Time-dependent regression analyses found that actual cumulative misonidazole dose was not related to duration of survival from start of treatment (p = 0.5). MISO dose expressed as a percent of expected dose was marginally related to increased survival measured from 14 weeks on on study (p = 0.1). No improvement in survival was observed with the addition of misonidazole to RT (64% of the patients on RT alone were alive at 18 months versus 54% of those on RT + MISO).