Cancer research
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Clinical Trial
Phase I pharmacokinetic and pharmacodynamic study of a new anthrapyrazole, CI-937 (DUP937).
We performed a phase I trial of CI-937 (DUP937), an anthrapyrazole, with the following objectives: (a) to determine the maximally tolerated dose in humans; (b) to define the toxicity spectrum of this agent; (c) to describe the pharmacokinetics of the drug; (d) to test a pharmacokinetics based hypothesis of dose escalation; and (e) to relate drug pharmacokinetics to pharmacodynamics. CI-937 was administered as a single bolus injection every 3-4 weeks at doses ranging from 3.6 to 25.2 mg/m2. Thirty-two patients and 57 courses were evaluable for toxicity. ⋯ Only dose and baseline neutrophil count predicted a percentage change in WBCs in a multifactor analysis. Dose and prior chemotherapy predicted percentage change in neutrophil count in a multifactor analysis. We conclude that the dose-limiting toxicity of CI-937 is neutropenia and that the recommended phase II starting dose is 22 mg/m2.