Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors

A. Russo, L. Gianni, T. J. Kinsella, R. W. Klecker, J. Jenkins, J. Rowland, E. Glatstein, J. B. Mitchell, J. Collins, C. Myers

Research output: Contribution to journalArticlepeer-review

Abstract

Previously, 5-bromodeoxyuridine (BrdUrd) has been shown to be an effective radiosensitizing agent in rapidly dividing cells. As part of a Phase I/II study to evaluate BrdUrd as a radiosensitizer in gliomas, the pharmacology was studied in eight patients. BrdUrd was infused using an i.v. route as a 12-hr constant infusion each day for as long as 14 days. BrdUrd steady-state arterial levels are described for three different infusional rates: 1.6 μmol/sq m/min (350 mg/sq m/12 hr) produced a steady state arterial level of 0.7 μM; 3.2 μmol/sq m/min (700 mg/sq m/12 hr) resulted in 2.1 μM; 5.9 μmol/sq m/min (650 mg/sq m/6 hr) showed a level of 3.9 μM. Because of myelosuppression, the highest tolerable dose for this intermittent long-term infusional therapy with BrdUrd appears to be 700 mg/sq m/12 hr. Contrary to the nonlinear pharmacokinetics of thymidine, 5-fluorouracil, and 5-fluorodeoxyuridine described previously, BrdUrd shows linear behavior in the range studied. BrdUrd still has promise as a radiosensitizer for gliomas in humans, but an alternative means of safe delivery into the carotid artery is needed. Because of an estimated 11- to 16-fold-higher local concentration, use of the intraarterial route could deliver optimum levels of BrdUrd to the tumor with minimal systemic toxicity.

Original languageEnglish
Pages (from-to)1702-1705
Number of pages4
JournalCancer Research
Volume44
Issue number4
Publication statusPublished - 1984

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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