A phase I and pharmacologic study of DMP 840 administered by 24-hour infusion

S. O'Reilly, S. D. Baker, S. Sartorius, E. K. Rowinsky, M. Finizio, G. M. Lubiniecki, L. B. Grochow, J. E. Gray, H. J. Pieniaszek, R. C. Donehower

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: DMP 840, a novel bisnaphthalimide, has demonstrated promising schedule dependent anti-tumor activity in vitro and in vivo against several tumor cell lines. A phase I study was conducted to evaluate the effect of a 24-hour infusion schedule repeated every three weeks, on the therapeutic efficacy of DMP 840. Patients and methods: Fourteen patients with refractory solid tumor malignancies were treated with DMP 840 at doses of 20, 40, 50 and 60 mg/m2. Results: A combination of neutropenia, thrombocytopenia and stomatitis were dose-limiting at doses of 50 and 60 mg/m2 in both minimally- and extensively-pretreated patients. In contrast, all courses at lower dose levels were well tolerated. Pharmacokinetic analysis demonstrated that DMP 840 had a prolonged terminal half life (median 39 hours; range 25-86) and that dose-limiting events were significantly related to several indices of systemic DMP 840 exposure (P < 0.01, Wilcoxon Rank Sum test). Conclusion: The recommended dose of DMP 840 for further disease oriented evaluation is 40 mg/m2 administered over 24 hours every three weeks. The infusion duration evaluated in this study did not result in a substantial increase in the tolerable dose compared to shorter, less cumbersome schedules.

Original languageEnglish (US)
Pages (from-to)101-104
Number of pages4
JournalAnnals of Oncology
Volume9
Issue number1
DOIs
StatePublished - Jan 1998

Keywords

  • DMP 840
  • Pharmacodynamics
  • Pharmacokinetics
  • Phase I

ASJC Scopus subject areas

  • Hematology
  • Oncology

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