title: The current status of drug development of hypoxic cell radiosensitizers and their potential role in gynecologic oncology.
abstract: Both laboratory and clinical data suggest that hypoxia contributes to the failure of radiotherapy to achieve local control of bulky gynecologic tumors. As part of a Phase I trial of hypoxic cell radiosensitizers, 19 women at Stanford University with advanced (n = 6) or recurrent (n = 13) pelvic neoplasms were treated with radiotherapy plus desmethylmisonidazole. Complete or partial response occurred in 42% of patients with some patients achieving local control for over 1 year. It is unknown if the sensitizer added to the results of radiotherapy alone. A Phase I trial of a theoretically superior sensitizer, SR-2508, is soon to begin. It is anticipated that the dose-limiting neurotoxicity seen with misonidazole and desmethylmisonidazole will either be eliminated or will occur at a much higher total dose of drug. Many patients with gynecologic tumors could potentially benefit from participation in the new drug trials.
mesh_terms: D000328:Adult; D000368:Aged; D004341:Drug Evaluation; D005260:Female; D005833:Genital Neoplasms, Female / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008875:Middle Aged; D008920:Misonidazole / Q000009:adverse effects / Q000031:analogs & derivatives / Q000633:toxicity*; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy; D009593:Nitroimidazoles / Q000633:toxicity*; D010100:Oxygen; D010166:Palliative Care; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011838:Radiation-Sensitizing Agents
chemical_list: D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008920:Misonidazole; C009997:desmethylmisonidazole; D010100:Oxygen