Treatment of malignant gliomas in adults with BCNU plus metronidazole

Twenty-six adult patients with astrocytomas were treated with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) 180-240 mg/m2 I.V. every 6-9 weeks, with metronidazole 1.5 g/m2 p.o. 12 h and 1 h before BCNU and again 6 h and 24 h after BCNU. Of twenty-two evaluable patients, 9 (41%) responded with evidence of reduced tumor size on CT scan, 3 (14%) stabilized and 10 (45%) failed. Patients with no prior chemotherapy or radiotherapy, good performance status, low grade tumors, and age less than or equal to 50 years had the highest response rates, although differences were not statistically significant. Median survival and duration of response have not been reached with a median follow-up time of ten months. Hematological toxicity was dose-limiting and was probably not augmented by the metronidazole. There was one death from infection that was possibly drug-related. Gastrointestinal toxicity was substantial, and was probably increased by the metronidazole. While the combination of BCNU and metronidazole were tolerable, the response rate seen was no higher than that noted for BCNU alone, and further studies using this dose-schedule are not recommended in astrocytomas.