z-logo
Premium
Final report on the united states phase i clinical trial of the hypoxic cell radiosensitizer, misonidazole (RO‐07‐0582; NSC #261037)
Author(s) -
Phillips Theodore L.,
Wasserman Todd H.,
Johnson Richard J.,
Levin Victor A.,
Vanraalte Gretchen
Publication year - 1981
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19811015)48:8<1697::aid-cncr2820480802>3.0.co;2-w
Subject(s) - misonidazole , medicine , nausea , vomiting , toxicity , discontinuation , dexamethasone , ototoxicity , gastroenterology , concomitant , phases of clinical research , anesthesia , pharmacology , chemotherapy , cisplatin , biochemistry , chemistry , in vitro
The hypoxic cell sensitizer misonidazole began phase I evaluation in the United States in July 1977. One hundred two patients received 104 individual courses of drug. Drug was administered from once to five times per week over time spans from one to six weeks. The individual doses ranged 1–5 g/m 2 , and 411 mean 4–6 hour serum levels were determined. The mean 4–6 hour serum level ranged from 30 μg/ml at 1 g/m 2 to 183 μg/ml at 5 g/m 2 . The major toxicity noted was neurologic; 49% of evaluable courses showed peripheral neuropathy, and 9% of evaluable courses showed central nervous system effects and/or ototoxicity. In addition, 48 of 102 patients exhibited some degree of nausea and vomiting. The concomitant administration of dexamethasone and phenytoin sodium appeared to lower the incidence of neuropathy. Observations of efficacy were made comparatively in five patients who had multiple lesions treated with and without misonidazole. All five showed increased response in the lesions treated with misonidazole. It is concluded that misonidazole is a reasonably safe and potentially effective hypoxic cell sensitizer whose dose‐limiting toxicity is neurologic.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here