International journal of radiation oncology, biology, physics
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Int. J. Radiat. Oncol. Biol. Phys. · Mar 1982
Initial pharmacology and toxicology of intravenous desmethylmisonidazole.
Since January 1981, 52 patients have entered the Radiation Therapy Oncology Group Phase I trial with intravenous (i.v.) desmethylmisonidazole (DMM). DMM is less lipophilic than misonidazole (MISO) and theoretically will be less neurotoxic due to lower penetration into neural tissue and more rapid elimination. The drug is administered intravenously to achieve the maximum drug concentration in tumor for a given dose. ⋯ This is in comparison to a 50% incidence in the RTOG Phase I study with oral MISO at doses of 12g/m2. There is not sufficient data to evaluate the relationship between neurotoxicity and drug exposure. Further patient accrual on this study is required to better define the properties of DMM.
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Int. J. Radiat. Oncol. Biol. Phys. · Mar 1982
Randomized Controlled Trial Clinical TrialHigh dose misonidazole with dexamethasone rescue: a possible approach to circumvent neurotoxicity.
With a view to modifying misonidazole (MISO) neurotoxicity, we initiated a randomized clinical study to assess a possible drug interaction and toxicity protection when dexamethasone (DXM) is administered concomittantly with MISO. The ongoing study consists of: 1. Pharmacokinetic evaluation; 2. ⋯ It is postulated that the mechanism of action of DXM is at the nerve cell membrane level, restoring and stabilizing cell surface properties. In future studies we will investigate the use of DXM with increasing doses of MISO above the recommended maximum dose of 12 gm/m2, hoping to achieve a higher tumor tissue level of MISO while avoiding unacceptable toxicity. The effect of Allopurinol on the plasma kinetics of MISO was studied in four additional patients, observing also no evidence of drug interaction.