Phase I clinical and pharmacokinetic study of flavopiridol in children with refractory solid tumors: A Children's Oncology Group Study

James A. Whitlock, Mark Krailo, Joel M Reid, Stacie L. Ruben, Matthew M. Ames, William Owen, Gregory Reaman

Research output: Contribution to journalArticle

29 Scopus citations


Purpose: To determine the dose-limiting toxicities, maximum-tolerated dose, and pharmacokinetics of the cyclin-dependent kinase inhibitor flavopiridol (NSC 649890) when administered as a 1-hour infusion over 3 consecutive days to children with recurrent or refractory solid tumors. Patients and Methods: Flavopiridol was administered as a 1-hour intravenous infusion daily for 3 consecutive days every 21 days, or when hematologic toxicity or any grade 2 or greater nonhematologic toxicity resolved. The starting dose was 37.5 mg/m 2/d. Dose escalation was in cohorts of three patients in a standard fashion until dose-limiting toxicity and the maximum-tolerated dose were determined. Flavopiridol levels were measured on days 1, 2, and 3. Results: Twenty-five children received flavopiridol at doses of 37.5 to 80 mg/m 2/day over 3 consecutive days. The maximum-tolerated dose was 62.5 mg/m2/d. The primary dose-limiting toxicities were neutropenia and diarrhea. No antitumor effect was observed in this population. Mean peak plasma concentrations of 3.71 and 9.11 μmol/L were achieved at the end of the 1-hour infusion, following dose escalation from 37.5 mg/m2 to 80 mg/m 2, respectively. The median flavopiridol plasma clearance was 8.0 L/h/m2 (range, 2.6 to 17.1 L/h/m2). Conclusion: The maximum-tolerated dose of flavopiridol in children, and the recommended phase II dose for pediatric studies, was 62.5 mg/m2/day when administered as a 1-hour infusion for 3 consecutive days. Dose-limiting toxicities of neutropenia and diarrhea were similar to those in adult studies.

Original languageEnglish (US)
Pages (from-to)9179-9186
Number of pages8
JournalJournal of Clinical Oncology
Issue number36
StatePublished - 2005


ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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