In the 1950's it was first observed that mammalian cells exposed to the 
halogenated deoxyuridines were more sensitive to ultraviolet light and radiation 
than untreated cells. This prompted early clinical trials with bromodeoxyuridine 
(BUdR) which showed mixed results. More recently, several Phase I studies, while 
establishing the feasibility of continuous intravenous (IV) infusion of BUdR, 
have reported significant dose limiting skin and bone marrow toxicities and have 
questioned the optimal method of BUdR delivery. To exploit the high mitotic 
activity of malignant gliomas relative to surrounding normal brain tissue, we 
have developed a permanently implantable infusion pump system for safe, 
continuous intraarterial (IA) internal carotid BUdR delivery. Since July 1985, 
23 patients with malignant brain tumors (18 grade 4, 5 grade 3) have been 
treated in a Phase I clinical trial using IA BUdR (400-600 mg/m2/day X 8 1/2 
weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy/day in 6 1/2 
weeks). Following initial biopsy/surgery the infusion pump system was implanted; 
BUdR infusion began 2 weeks prior to and continued throughout the 6 1/2 week 
course of radiotherapy. There have been no vascular complications. Side-effects 
in all patients have included varying degrees of anorexia, fatigue, ipsilateral 
forehead dermatitis, blepharitis, and conjunctivitis. Myelosuppression requiring 
dose reduction occurred in one patient. An overall Kaplan-Meier estimated median 
survival of 20 months has been achieved. As in larger controlled series, 
histologic grade and age are prognostically significant. We have shown in a 
Phase I study that IA BUdR radiosensitization is safe, tolerable, may lead to 
improved survival, and appears to be an efficacious primary treatment of 
malignant gliomas.