Phase I trial of the hypoxic cell radiosensitizer SR-2508: The results of the five to six week drug schedule

C. Norman Coleman, Todd H. Wasserman, Raul C. Urtasun, Joanne Halsey, V. Kate Hirst, Steven Hancock, Theodore L. Phillips

Research output: Contribution to journalArticle

Abstract

Sixty-five patients were entered on the long schedule of the Phase I trial of SR-2508. The planned total doses ranged from 30 to 40.8 g/m2 using various treatment schema including daily, split course, and every-other-day schedules. The individual dose size was 2 g/m2 for 56 patients and 1.7 g/m2 for nine. In contrast to misonidazole and desmethylmisonidazole, more SR-2508 can be administered as the duration of therapy is lengthened. All six patients on the 30 g/m2 step tolerated the drug without toxicity. This total dose was not achievable in the three week schedule. Additionally, a number of patients did not develop neuropathy at a cumulative dose of 40.8 g/m2. Although the analysis is not yet complete, a given patient's drug exposure as measured by their total AUC (mMxhr), defined as the area-under-the-curve of serum concentration of SR-2508 vs. time for a single dose times the number of doses given, is useful in predicting toxicity for that patient. The recommended starting schedule for the Phase II and III trials is 34 g/m' over a 6 week period (2 g/m2 every other day). A total AUC of approximately 39 mMxhr should be tolerable. The drug regimen must be altered for patients who have a high AUC. Therefore, it is mandatory to have an accurate and rapid pharmacokinetic analysis for each patient. The clinical efficacy of the hypoxic cell sensitizers remains to be proven. However, using the guidelines derived from the Phase I trial, SR-2508 should be a relatively safe drug, producing minor or no toxicity.

Original languageEnglish (US)
Pages (from-to)1105-1108
Number of pages4
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume12
Issue number7 PART 1
DOIs
StatePublished - 1986
Externally publishedYes

Fingerprint

Etanidazole
schedules
Appointments and Schedules
drugs
Pharmaceutical Preparations
dosage
Area Under Curve
toxicity
Misonidazole
Drug-Related Side Effects and Adverse Reactions
serums
therapy
Pharmacokinetics
Guidelines

Keywords

  • 2-nitroimidazoles
  • Hypoxic cell sensitizers
  • Misonidazole
  • Neuropathy
  • Pharmacokinetics
  • Radiosensitizers
  • SR-2508

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Norman Coleman, C., Wasserman, T. H., Urtasun, R. C., Halsey, J., Hirst, V. K., Hancock, S., & Phillips, T. L. (1986). Phase I trial of the hypoxic cell radiosensitizer SR-2508: The results of the five to six week drug schedule. International Journal of Radiation Oncology, Biology, Physics, 12(7 PART 1), 1105-1108. https://doi.org/10.1016/0360-3016(86)90236-1

Phase I trial of the hypoxic cell radiosensitizer SR-2508 : The results of the five to six week drug schedule. / Norman Coleman, C.; Wasserman, Todd H.; Urtasun, Raul C.; Halsey, Joanne; Hirst, V. Kate; Hancock, Steven; Phillips, Theodore L.

In: International Journal of Radiation Oncology, Biology, Physics, Vol. 12, No. 7 PART 1, 1986, p. 1105-1108.

Research output: Contribution to journalArticle

Norman Coleman, C, Wasserman, TH, Urtasun, RC, Halsey, J, Hirst, VK, Hancock, S & Phillips, TL 1986, 'Phase I trial of the hypoxic cell radiosensitizer SR-2508: The results of the five to six week drug schedule', International Journal of Radiation Oncology, Biology, Physics, vol. 12, no. 7 PART 1, pp. 1105-1108. https://doi.org/10.1016/0360-3016(86)90236-1
Norman Coleman, C. ; Wasserman, Todd H. ; Urtasun, Raul C. ; Halsey, Joanne ; Hirst, V. Kate ; Hancock, Steven ; Phillips, Theodore L. / Phase I trial of the hypoxic cell radiosensitizer SR-2508 : The results of the five to six week drug schedule. In: International Journal of Radiation Oncology, Biology, Physics. 1986 ; Vol. 12, No. 7 PART 1. pp. 1105-1108.
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