Initial report of the phase I trial of the hypoxic cell radiosensitizer SR-2508

C. Norman Coleman, Raul C. Urtasun, Todd H. Wasserman, Steven Hancock, John W. Harris, Joanne Halsey, V. Kate Hirst

Research output: Contribution to journalArticle

Abstract

From March 15, through August 31, 1983, 37 patients have been entered on the RTOG Phase I trial of SR-2508. The drug was given intravenously three times weekly for three weeks. The starting total dose was 11.7 g/m2 and the highest total dose given was 32 g/m2. The lower lipophilicity of SR-2508 has produced the expected decrease in terminal half-life (5.4 hrs) of drug excretion and increase in total drug excreted unchanged in the urine (71%) compared to misouidazole or desmethylmisonidazole. The maximum single dose (3.7 g/m2) administered was well tolerated. With multiple doses peripheral neuropathy is the dose-limiting toxicity. The lowest cumulative dose producing toxicity was 21.6 g/m2, the highest non-toxic dose was 29.7 g/m2. The use of an individual patient's drug exposure as measured by the area under the curve of drug concentration vs time may be an excellent predictor of toxicity. This may eventually permit individualization of dose and prevention of serious toxicity. A single dose of 2 g/m2 will produce a tumor concentration of drug (approx. 100 μg/ml) that will yield a sensitizer enhancement ratio of 1.5 to 1.7. Using a starting dose of 2 g/m2 three times weekly, patients are now being studied on a five week drug schedule to further evaluate predictability of drug toxicity in preparation for clinical trials of drug efficacy.

Original languageEnglish (US)
Pages (from-to)1749-1753
Number of pages5
JournalInternational journal of radiation oncology, biology, physics
Volume10
Issue number9
DOIs
StatePublished - Sep 1984

Keywords

  • Nitroimidazoles
  • Radiosensitizers
  • Radiotherapy

ASJC Scopus subject areas

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

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    Coleman, C. N., Urtasun, R. C., Wasserman, T. H., Hancock, S., Harris, J. W., Halsey, J., & Hirst, V. K. (1984). Initial report of the phase I trial of the hypoxic cell radiosensitizer SR-2508. International journal of radiation oncology, biology, physics, 10(9), 1749-1753. https://doi.org/10.1016/0360-3016(84)90542-X