The current status of drug development of hypoxic cell radiosensitizers and their potential role in gynecologic oncology.
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.
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
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008920:Misonidazole; C009997:desmethylmisonidazole; D010100:Oxygen