Clinical trial of intravenous infusion of bromodeoxyuridine (BUdR) for radiosensitization of malignant brain tumors.

Bromodeoxyuridine (BUdR) is a radiosensitizer that can be incorporated into cellular DNA as a substitute for thymidine at the time of DNA synthesis. As the steady-state arterial concentration of BUdR given by means of intravenous infusion was recently presented, the possibility of revival of BUdR as a radiosensitizer administered by the intravenous route was suggested. Based on the experience of BAR therapy and phase-I studies by NIH and UCSF, 12 hours of BUdR at a dose of 800-1,000 mg/m2 for five days a week was given to 23 patients with primary and secondary malignant brain tumors during radiation therapy. Radiation therapy was planned at a weekly dose of 10 Gy for five to six weeks. Fifteen patients received 1,000 mg/m2 of BUdR; six of them tolerated more than three weeks of treatment. In eight patients given doses of 800 mg/m2, five patients tolerated more than three weeks. The most remarkable toxic effects were myelosuppression and stomatitis, which were major obstacles to maintaining the schedule. More than 50% reduction of tumor volume was obtained in five of 12 cases of evaluated gliomas (42%) and three of four cases of metastatic tumors (75%). The median time to tumor progression in seven patients with glioblastoma was 37 weeks.