RTOG #89-06: A phase I study to evaluate intraoperative radiation therapy and the hypoxic cell sensitizer etanidazole in locally advanced malignancies

Francine E. Halberg, Dennis Cosmatis, Leonard L. Gunderson, R. Dirk Noyes, Gerald R. Hanks, Laura Buswell, David M. Nagorney, C. Norman Coleman

Research output: Contribution to journalArticle

Abstract

Purpose: To identify the maximum tolerated dose of the oxygen mimetic radiation sensitizer Etanidazole in the setting of surgery and intraoperative radiation therapy. 12 grams/meter2 was the maximum chosen target dose based on tolerance from other trials. Methods and Materials: 42 patients were entered in an escalating dose scheme, 5.5, 7.5, 9, 10.5, and 12.0 grams/meter2. Etanidazole was given via intravenous infusion over 15 minutes, followed within 20 to 30 minutes by intraoperative radiation therapy. Multiple tissue samples from tumor, tumor bed, and/or normal tissue were obtained with simultaneous plasma samples. Etanidazole concentrations in tissue and serum were determined in 33 of the 42 patients. Results: The median time to maximum serum concentration was 25 minutes. Median time to maximum tissue concentration was 40 minutes. Tissue concentrations began falling approximately one hour after infusion. Acute drug toxicities were minimal. Toxicities reported during follow-up related to surgery and/or radiation, not to drug. The concentration of sensitizer in tumor/tumor bed tissues was ten-fold greater than in previous trials. A sensitizer enhancement ratio for the hypoxic cells of 2 to 2.5 is projected. Conclusion: On the basis of tissue biopsy information, intraoperative radiation therapy will be given 40 minutes after the start of the 15 minute infusion allowing time for maximum intracellular uptake into tumor cells. In view of these findings, a Phase III trial testing etanidazole with intraoperative radiation therapy will be conducted. The tolerable single dose level of 12 grams/meter2 has potential with other high-dose radiation settings such as brachy-therapy or stereotactic radiosurgery.

Original languageEnglish (US)
Pages (from-to)201-206
Number of pages6
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume28
Issue number1
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Etanidazole
radiation therapy
Radiotherapy
tumors
dosage
Neoplasms
surgery
toxicity
serums
beds
drugs
radiation
Accidental Falls
Radiation
Radiation-Sensitizing Agents
Maximum Tolerated Dose
Radiosurgery
Drug-Related Side Effects and Adverse Reactions
Serum
falling

Keywords

  • Enhancement
  • Etanidazole
  • Hypoxic cell
  • Intraoperative radiotherapy
  • Radiation sensitizer
  • SR-2508

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

RTOG #89-06 : A phase I study to evaluate intraoperative radiation therapy and the hypoxic cell sensitizer etanidazole in locally advanced malignancies. / Halberg, Francine E.; Cosmatis, Dennis; Gunderson, Leonard L.; Dirk Noyes, R.; Hanks, Gerald R.; Buswell, Laura; Nagorney, David M.; Coleman, C. Norman.

In: International Journal of Radiation Oncology, Biology, Physics, Vol. 28, No. 1, 01.01.1994, p. 201-206.

Research output: Contribution to journalArticle

Halberg, Francine E. ; Cosmatis, Dennis ; Gunderson, Leonard L. ; Dirk Noyes, R. ; Hanks, Gerald R. ; Buswell, Laura ; Nagorney, David M. ; Coleman, C. Norman. / RTOG #89-06 : A phase I study to evaluate intraoperative radiation therapy and the hypoxic cell sensitizer etanidazole in locally advanced malignancies. In: International Journal of Radiation Oncology, Biology, Physics. 1994 ; Vol. 28, No. 1. pp. 201-206.
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