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

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Summary

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 ≥ 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.

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Correspondence to Karl Bélanger.

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Bélanger, K., Jolivet, J., Maroun, J. et al. Phase I pharmacokinetic study of DUP-937, a new anthrapyrazole. Invest New Drugs 11, 301–308 (1993). https://doi.org/10.1007/BF00874428

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Key words

  • anthrapyrazole
  • DUP-937
  • phase I
  • pharmacokinetics