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

Annals of Oncology : Official Journal of the European Society for Medical Oncology
S O'ReillyR C Donehower

Abstract

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. Fourteen patients with refractory solid tumor malignancies were treated with DMP 840 at doses of 20, 40, 50 and 60 mg/m2. 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). The recommended dose of DMP 840 for further disease oriented evaluations 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.

Citations

Mar 3, 2004·Chemical & Pharmaceutical Bulletin·Jaskiran KaurRamesh Chandra
Mar 15, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H J BursteinE P Winer
Feb 7, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M A Villalona-CaleroE K Rowinsky
Aug 12, 2005·Dalton Transactions : an International Journal of Inorganic Chemistry·Susan L WoodhouseLouis M Rendina
Jun 18, 2020·Breast Cancer : Targets and Therapy·Sundaram SubramanianImran Ahmad
Feb 1, 2008·Journal of Medicinal Chemistry·Ippolito AntoniniGloria Cristalli

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