Final report of the phase i trial of the hypoxic cell radiosensitizer SR 2508 (etanidazole) radiation therapy oncology group 83-03

C. Norman Coleman, Todd H. Wasserman, Raul C. Urtasun, Joanne Halsey, Lisa Noll, Steven Hancock, Theodore L. Phillips

Research output: Contribution to journalArticlepeer-review

Abstract

In a Phase I trial SR 2508 was administered by rapid intravenous infusion to 102 patients receiving radiation therapy. The dose-limiting toxicity was peripheral sensory neuropathy (PN) which was related to the cumulative dose administered. The highest single daily dose, 3.7 g/m2, was tolerated without toxicity. The lowest cumulative toxic dose was 21.6 g/m2, and the highest non-toxic dose was 40.8 g/m2. Grade 1 neuropathies were mild and self-limited; grade 2 neuropathies were long-lasting and debilitating. In a retrospective analysis, the risk of developing neurotoxicity was related to the cumulative drug exposure calculated by the area-under-the-curve (AUC) of plasma concentration versus time. There was an increased incidence of neuropathy in patients with a cumulative AUC of ≥36 mM-hr. At a total dose of 34 g/m2 over 6 weeks, the incidence of Grade 1 neuropathy was approximately 30%; no grade 2 neuropathy occurred at this dose and schedule. Additional toxicities observed included nausea and vomiting (6%), skin rash (4%), and transient arthralgias (3%). One patient had transient abnormalities in liver function tests of unknown etiology. (In a more recent Phase II trial neutropenia has been observed which may be related to SR2508). Approximately three times more SR 2508 is tolerable compared to misonidazole, and it appears that severe neuropathy can be avoided by monitoring individual patient pharmacokinetic parameters. Evaluation of the efficacy of this hypoxic cell sensitizer is in progress.

Original languageEnglish (US)
Pages (from-to)389-393
Number of pages5
JournalInternational journal of radiation oncology, biology, physics
Volume18
Issue number2
DOIs
StatePublished - Feb 1990

Keywords

  • 2-nitroimidazoles
  • Etanidazole
  • Hypoxic cell sensitizers
  • Misonidazole
  • Neuropathy
  • Pharmacokinetics
  • Radiosensitizers
  • SR2508

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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