Misonidazole peripheral neuropathy: its relationship to plasma concentration and other drugs

The data from 44 patients with documented glioblastoma who received 1.5 g/m2 of misonidazole twice weekly in conjunction with whole brain radiotherapy (total dose 6000 rad) was analyzed for factors associated with the development of peripheral neuropathy. The average total cumulative dose of misonidazole was 16.9 g/m2 and mild to moderate reversible peripheral neuropathy developed in 18% of patients. Peripheral neuropathy was positively associated with: 1) evidence of residual misonidazole in pretreatment plasma samples (> 10 microgram/ml), 2) elevated plasma concentrations of misonidazole on the day following treatment (> 25% of 4-hour plasma concentration), and 3) a prolonged plasma half-life (an average of 25% greater in patients developing peripheral neuropathy). The use of corticosteriods was negatively associated with the development of peripheral neuropathy and appeared to confer some protection. Age, sex, total dose of misonidazole, 4-hour plasma concentration (namely, at the time of radiotherapy), or the receipt of phenytoin or barbiturates was not related to the development of peripheral neuropathy. Monitoring of plasma misonidazole concentrations during treatment in conjunction with careful examination of the patient may result in a reduction of the incidence or severity of peripheral neuropathy.