Is misonidazole neurotoxicity altered by the use of phenytoin and/or dexamethasone in RTOG 79-18 and RTOG 79-16?
An analysis of Misonidazole (MISO) neurotoxicity in RTOG 79-16 and RTOG 79-18 was undertaken to evaluate the incidence of neurotoxicity relative to dexamethasone dose and phenytoin use. MISO was administered as follows: 79-16 arm A, 1 gm/m2 5 days a week for a total of 10 gm/m2 in 2 weeks; 79-16 arm B, 2 gm/m2 twice weekly for a total of 12 gm/m2 in 3 weeks; and 79-18, 2.5 gm/m2 once a week for a total of 15 gm/m2 in 6 weeks. Practically all patients were on dexamethasone, and 240 out of 550 were on phenytoin for seizures. CNS toxicity and ototoxicity rates were no different between treatment groups with overall rates of 2.7 and 1.1%, respectively. Peripheral neuropathy (PN) was 5.1% in 79-16 arm A, 5.9% in 79-16 arm B, and 8.7% in 79-18. Phenytoin did not significantly alter CNS and PN toxicity rates. All ototoxicities occurred in patients not on phenytoin. There was no correlation between dexamethasone dose and incidence of neurotoxicity within each study. However, the incidence of (PN) for the combined studies was 6.4% (35/550) which is lower than 18.9% (85/449) for non-brain Phase III protocols where patients are rarely, if ever, on dexamethasone or other corticosteroids. Four hour and 24 hour plasma MISO levels, and 24 hour/4 hour MISO ratios did not correlate with toxicity.
D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D002986:Clinical Trials as Topic; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000627:therapeutic use / Q000633:toxicity*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control; D009593:Nitroimidazoles / Q000633:toxicity*; D010672:Phenytoin / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use / Q000633:toxicity*
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D010672:Phenytoin; D003907:Dexamethasone; D008920:Misonidazole