RTOG #89-06: A phase I study to evaluate intraoperative radiation therapy and the hypoxic cell sensitizer etanidazole in locally advanced malignancies

摘要: Abstract Purpose : To identify the maximum tolerated dose of oxygen mimetic radiation sensitizer Etanidazole in setting surgery and intraoperative therapy. 12 grams/meter2 was chosen target based on tolerance from other trials. Methods Materials 42 patients were entered an escalating scheme, 5.5, 7.5, 9, 10.5, 12.0 grams/meter2. given via intravenous infusion over 15 minutes, followed within 20 to 30 minutes by Multiple tissue samples tumor, tumor bed, and/or normal obtained with simultaneous plasma samples. concentrations serum determined 33 patients. Results The median time concentration 25 minutes. Median 40 Tissue began falling approximately one hour after infusion. Acute drug toxicities minimal. Toxicities reported during follow-up related radiation, not drug. tumor/tumor bed tissues ten-fold greater than previous A enhancement ratio for hypoxic cells 2 2.5 is projected. Conclusion On basis biopsy information, therapy will be start minute allowing intracellular uptake into cells. In view these findings, a Phase III trial testing etanidazole conducted. tolerable single level has potential high-dose settings such as brachy-therapy or stereotactic radiosurgery.