Phase I Trial of Intravenous L-Phenylalanine Mustard plus the Sensitizer Misonidazole

C. Norman Coleman, Michael K. Friedman, Charlotte Jacobs, Joanne Halsey, Robert Ignoffo, Stephen Leibel, V. Kate Hirst, Melanie Gribble, Steven K. Carter, Theodore L. Phillips, C. Norman Coleman, Michael K. Friedman, Charlotte Jacobs, Joanne Halsey, Robert Ignoffo, Stephen Leibel, V. Kate Hirst, Melanie Gribble, Steven K. Carter, Theodore L. PhillipsC. Norman Coleman, Michael K. Friedman, Charlotte Jacobs, Joanne Halsey, Robert Ignoffo, Stephen Leibel, V. Kate Hirst, Melanie Gribble, Steven K. Carter, Theodore L. Phillips, C. Norman Coleman

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Misonidazole (MISO), a hypoxic cell radiosensitizer, has been shown in vivo to enhance tumor cell killing by melphalan (LPAM) with little or no enhancement of normal tissue injury. A Phase I trial was conducted using MISO p.o. 2 hr before i.v. LPAM. The highest closes used were the single maximum tolerated closes of MISO, 4 g/sq m, and LPAM, 0.6 mg/kg. Thirty-five patients were entered; 30 were evaluable for assessment of hematological toxicity, which was predicted to be the dose-limiting toxicity. The median age was 60 years (range, 28 to 72 years). Mild to moderate nausea and vomiting occurred in 80% of patients. Five developed serious hematological toxicity defined as nadir white blood cell count < 1000/cu mm, platelets < 20,000/cu mm or 4-week posttreatment white blood cell count < 2000/cu mm, platelets < 50,000/cu mm. Four of the toxicities occurred at the LPAM (Jose of 0.6 mg/kg but were independent of MISO dose. One patient died of infection. Two patients whose tumor demonstrated an objective response to therapy and 10 others with disease stabilization received additional courses. Four patients developed mild MISO neuropathy. Pharmacokinetic studies demonstrated that MISO did not appear to affect the pharmacokinetics of LPAM in plasma. Both LPAM and MISO can be given safely at their individual maximum tolerated dose. This combination will proceed to Phase II trials.

Original languageEnglish (US)
Pages (from-to)5022-5025
Number of pages4
JournalCancer Research
Volume43
Issue number10
StatePublished - Oct 1 1983
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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