Final report of the phase I trial of continuous infusion etanidazole (SR 2508): A radiation therapy oncology group study

C. Norman Coleman, Lisa Noll, Nancy Riese, Lori Buswell, Anthony E. Howes, Jay S. Loeffler, Eben Alexander, Patrick Wen, Jay R. Harris, Robert A. Kramer, Selwyn J. Hurwitz, Tamlyn Yee Neben, Perry Grigsby

Research output: Contribution to journalArticle

Abstract

Seventy-eight patients have been treated on a Phase I trial using continuous infusion etanidazole while undergoing brachytherapy for locally advanced tumors. There were two sequential schemata, the first treated 63 patients with doses ranging from 8-23 g/m2 over 48 hr and the second treated 15 patients with doses ranging from 20-23 g/m2 over 96 hr. The tumor sites were: brain (n = 42), cervix (n = 22), and breast (n = 14). Patients received a loading dose of etanidazole of 2 g/m2 followed by a continuous infusion for a total of 48 or 96 hr while radioactive implants were in place. Of the 63 patients in the 48-hr study, 52 were entered at doses of ≤ 21 g/m2 and there were no definite neuropathies but two patients with the cramping/arthralgia syndrome. Of the 11 patients entered at 22-23 g/m2, 1 patient had symptoms of peripheral neuropathy (Grade II) and 6 had the cramping/arthralgia syndrome. This is a new syndrome, distinct from the peripheral neuropathy, characterized by transient alterations in sensations consisting of cramping, arthralgias, or tingling that resolved completely at intervals varying from a few hours to about 1 week post-treatment. The cramping/arthralgia syndrome limited dose escalation; therefore, the maximum tolerated dose over 48 hr was determined to be 20-21 g/m2. The 96-hr infusion was limited to patients with recurrent gliomas undergoing stereotactic Implantation. To date, 15 patients have been treated with doses of 20-23 g/m2. No toxicity was encountered at doses 22 g/m2. At 23 g/m2, one patient developed Grade III neuropathy and three patients had mild cramping/arthralgia syndrome, for whom the drug was discontinued. Therefore, it appears the maximum tolerated dose at 96 hr will be approximately 23 g/m2, which is 10-15% higher than for the 48-hr infusion.

Original languageEnglish (US)
Pages (from-to)577-580
Number of pages4
JournalInternational journal of radiation oncology, biology, physics
Volume22
Issue number3
DOIs
StatePublished - 1992

Keywords

  • 2-nitroimidazoles
  • Brachytherapy
  • Chemical modifiers
  • Continuous infusion
  • Etanidazole
  • Hypoxic cell sensitizers
  • Radiosensitizers
  • SR 2508

ASJC Scopus subject areas

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

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  • Cite this

    Norman Coleman, C., Noll, L., Riese, N., Buswell, L., Howes, A. E., Loeffler, J. S., Alexander, E., Wen, P., Harris, J. R., Kramer, R. A., Hurwitz, S. J., Neben, T. Y., & Grigsby, P. (1992). Final report of the phase I trial of continuous infusion etanidazole (SR 2508): A radiation therapy oncology group study. International journal of radiation oncology, biology, physics, 22(3), 577-580. https://doi.org/10.1016/0360-3016(92)90880-Q