title: Misonidazole combined with large-fraction pelvic irradiation in the treatment of patients with advanced pelvic malignancies. Preliminary report of an ongoing RTOG phase I-II study.
abstract: Between October 1979 and January 1982, a total of 39 cases were entered on a nonrandomized phase I-II protocol for the evaluation of misonidazole combined with radiation in the treatment of patients with advanced pelvic malignancies of multiple gynecological and gastrointestinal origin. Patients were treated with pelvic irradiation using a dose of 1000 rad in one fraction every 4 weeks for a total of three treatments. Oral misonidazole at a dose of 4 g/m2, was administered 4-6 hours prior to the radiation treatment (total dose, 12 g/m2). Of the 39 patients entered, 25 have completed the three doses of radiation and have had at least one follow-up after the third treatment. Eight patients have had insufficient follow-up information for evaluation and five patients did not complete three doses of radiation but have follow-up. One patient was excluded from the study. Among the 30 patients with follow-up, there were four complete responses (13.3%) and seven partial responses (23.3%). Two patients showed no response, and 17 experienced progression of disease. Follow-up time ranged from 2 to 16 months. The most frequent toxicity in the study has been nausea and vomiting. There were eight cases of neurotoxicity reported: ototoxicity grade 1 (one patient), peripheral neuropathy grades 1 and 2 (six patients), and C.N.S. toxicity grade 2 (one patient). Toxicity from radiation was difficult to separate from the presenting symptomatology. In the 30 patients with follow-up information, eight cases of abdominal sequelae were seen with five of them major complications (perforation, obstruction, and abscess). Early information from the study indicates the following: The most frequent morbidity at this point is acute nausea and vomiting. This level of nausea is consistent with the protocol dose of misonidazole. From the evaluable patients, 5/30 (17%) have developed major bowel problems requiring surgery. At the time of this report, this protocol remains open for case accession.
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008875:Middle Aged; D008920:Misonidazole / Q000009:adverse effects / Q000627:therapeutic use*; D009593:Nitroimidazoles / Q000627:therapeutic use*; D010166:Palliative Care; D010386:Pelvic Neoplasms / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects; D011882:Radiotherapy, High-Energy
chemical_list: D009593:Nitroimidazoles; D008920:Misonidazole