Phase I study of intravenous bromodeoxyuridine used concomitantly with radiation therapy in patients with primary malignant brain tumors.

We report here the results of a Phase I study conducted to determine the toxicity and serum levels that could be tolerated by patients receiving i.v. bromodeoxyuridine (BUdR) concomitantly with radiation therapy. Because of severe thrombocytopenia and leukopenia that was produced in three patients treated by a 96 hour infusion of BUdR at a dose of 1.5 g/m2/24 hours, the dose was reduced to 0.8 g/m2/24 hours in these patients and the remaining 9 patients in the study group. Even at this dosage, myelotoxicity was observed. BUdR levels were measured by an isocratic high performance liquid chromatographic (HPLC) method developed for this study. Results of in vitro studies conducted by others suggest that serum levels produced in our patients by administration of doses of 0.6 to 0.8 g/m2/24 hours should be adequate to achieve a therapeutic effect.