Phase I pharmacokinetic study of DUP-937, a new anthrapyrazole

Invest New Drugs. 1993 Nov;11(4):301-8. doi: 10.1007/BF00874428.

Abstract

DUP-937 is a new anthrapyrazole intercalator that inhibits DNA synthesis. A phase I trial was conducted in which DUP-937 was given in an intravenous bolus weekly for 3 weeks. Cycles were repeated every 5 weeks. Twenty men and 13 women with median ECOG performance status of 1 completed 74 cycles. The starting dose was 0.55 mg/m2/week and doses were escalated to 16 mg/m2/week. Non-hematological toxicity was generally mild or moderate and consisted mainly of gastro-intestinal effects, fatigue, alopecia and local reactions. Grade 3 neutropenia was first documented at 7.36 mg/m2 and became more common at higher dose levels. Three of four patients had > or = grade 3 neutropenia at the 16 mg/m2 dose level. Thrombocytopenia was minimal. The dose-limiting toxicity was neutropenia and the maximum tolerated dose was 16 mg/m2 weekly for 3 weeks. Mean area under the curve (AUC) values increased with dose. Linear pharmacokinetics were observed as total body clearance (CLtb), half-life (t1/2) and volume of distribution (Vss) did not change with increasing doses. One partial remission in a patient with prostate carcinoma was documented.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anthraquinones / administration & dosage
  • Anthraquinones / adverse effects
  • Anthraquinones / pharmacokinetics*
  • Anthraquinones / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Hematologic Tests
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Models, Biological
  • Neoplasms / drug therapy*
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyrazoles / pharmacokinetics*
  • Pyrazoles / therapeutic use*

Substances

  • Anthraquinones
  • Antineoplastic Agents
  • Pyrazoles
  • teloxantrone