Phase I trial and pharmacokinetic study of intravenous and oral α-Difluoromethylornithine

Constance A. Griffin, Milan Slavik, Shu Chean Chien, Joachim Hermann, George Thompson, Oscar Blanc, Gordon D. Luk, Stephen B. Baylin, Martin D. Abeloff

Research output: Contribution to journalArticle


Eflornithine-HCl (α-difluoromethylornithine or DFMO), an irreversible inhibitor of ornithine decarboxylase, blocks polyamine synthesis and has demonstrated antitumor activity in cell culture and animal tumor models. This phase I study was designed to determine and compare toxicity and the maximally tolerated dose of a 4-day course of DFMO given to patients in oral, continuous intravenous infusion or pulse intravenous infusion forms. Twenty-four patients were entered into this study: 8 received intravenous pulse drug, 10 intravenous continuous infusion of drug, and 6 oral DFMO. The most frequent toxicity was nausea and vomiting which occurred in 9 courses of oral drug. Only two patients receiving intravenous DFMO had nausea and vomiting. Clinically significant thrombocytopenia and audiometric abnormalities were not encountered in contrast to previous experience with 28-day courses of oral DFMO. The maximally tolerated dose of a four-day course of oral DFMO was 3.75 gm/M2 every 6 hours. The maximally tolerated dose of intravenous pulse and continuous infusion DFMO was not attained. Pharmacokinetic studies demonstrated that the intravenous schedules achieved higher plasma levels of DFMO than those previously obtained with chronic oral dosing.

Original languageEnglish (US)
Pages (from-to)177-186
Number of pages10
JournalInvestigational New Drugs
Issue number2
StatePublished - Jun 1987


  • pharmacokinetics
  • phase I study
  • polyamines
  • α-difluoromethylornithine

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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    Griffin, C. A., Slavik, M., Chien, S. C., Hermann, J., Thompson, G., Blanc, O., Luk, G. D., Baylin, S. B., & Abeloff, M. D. (1987). Phase I trial and pharmacokinetic study of intravenous and oral α-Difluoromethylornithine. Investigational New Drugs, 5(2), 177-186.