Intra-arterial bromodeoxyuridine radiosensitization of malignant gliomas

Journal Article · Wed Aug 01 00:00:00 EDT 1990 · International Journal of Radiation Oncology, Biology and Physics; (USA)

DOI:https://doi.org/10.1016/0360-3016(90)90552-U· OSTI ID:6427432

Hegarty, T J; Thornton, A F; Diaz, R F; Chandler, W F; Ensminger, W D; Junck, L; Page, M A; Gebarski, S S; Hood, T W; Stetson, P L ^[1]

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1. Univ. of Michigan Medical Center, Ann Arbor (USA)

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.

• OSTI ID: 6427432
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (USA), Vol. 19:2; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
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BUDR
RADIOSENSITIVITY EFFECTS
GLIOMAS
COMBINED THERAPY
SIDE EFFECTS
SURVIVAL CURVES
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ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
RIBOSIDES
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