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

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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

Fingerprint

Bromodeoxyuridine
Brain Neoplasms
Pharmacology
Glioma
Floxuridine
Radiation-Sensitizing Agents
Carotid Arteries
Fluorouracil
Thymidine
Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Russo, A., Gianni, L., Kinsella, T. J., Klecker, R. W., Jenkins, J., Rowland, J., ... Myers, C. (1984). Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors. Cancer Research, 44(4), 1702-1705.

Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors. / Russo, A.; Gianni, L.; Kinsella, T. J.; Klecker, R. W.; Jenkins, J.; Rowland, J.; Glatstein, E.; Mitchell, J. B.; Collins, J.; Myers, C.

In: Cancer Research, Vol. 44, No. 4, 1984, p. 1702-1705.

Research output: Contribution to journalArticle

Russo, A, Gianni, L, Kinsella, TJ, Klecker, RW, Jenkins, J, Rowland, J, Glatstein, E, Mitchell, JB, Collins, J & Myers, C 1984, 'Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors', Cancer Research, vol. 44, no. 4, pp. 1702-1705.
Russo A, Gianni L, Kinsella TJ, Klecker RW, Jenkins J, Rowland J et al. Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors. Cancer Research. 1984;44(4):1702-1705.
Russo, A. ; Gianni, L. ; Kinsella, T. J. ; Klecker, R. W. ; Jenkins, J. ; Rowland, J. ; Glatstein, E. ; Mitchell, J. B. ; Collins, J. ; Myers, C. / Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors. In: Cancer Research. 1984 ; Vol. 44, No. 4. pp. 1702-1705.
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