Phase I trial and pharmacokinetics of gemcitabine in children with advanced solid tumors

Joel M. Reid, Wenchun Qu, Stephanie L. Safgren, Matthew M. Ames, Mark D. Krailo, Nita L. Seibel, John Kuttesch, John Holcenberg

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64 Scopus citations

Abstract

Purpose: To determine the maximum tolerated dose, toxicity, and pharmacokinetics of gemcitabine in children with refractory solid tumors. Patients and Methods: Gemcitabine was given as a 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks, to 42 patients aged 1 to 21 years. Doses of 1,000, 1,200 and 1,500 mg/m2 were administered for 3 weeks. Subsequently, gemcitabine was given for only 2 consecutive weeks at 1,500, 1,800, and 2,100 mg/m2. Plasma concentrations of gemcitabine and its metabolite, 2′2′-difluorodeoxyuridine, were measured in 28 patients. Results: Forty patients who received 132 courses of gemcitabine were assessable for toxicity. The maximum tolerated dose of gemcitabine given weekly for 3 weeks was 1,200 mg/m2. Dose-limiting toxicity was not seen in one-third of children treated at any doses given for 2 weeks. The major toxicity was myelosuppression in three of five patients at 1,500 mg/m2 for 3 weeks, and one of seven patients at 1,800 mg/m2 for 2 weeks. Other serious adverse events were somnolence, fever and hypotension, and rash in three patients. Gemcitabine plasma concentration-time data were fit to a one- (n = 5) or two-compartment (n = 23) open model. Mean gemcitabine clearance and half-life values were 2,140 mL/min/m2 and 13.7 minutes, respectively. One patient with pancreatic cancer had a partial response. Seven patients had stable disease for 2 to 17 months. Conclusion: Gemcitabine given by 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks was tolerated well by children at doses of 2,100 mg/m2 and 1,200 mg/m2, respectively.

Original languageEnglish (US)
Pages (from-to)2445-2451
Number of pages7
JournalJournal of Clinical Oncology
Volume22
Issue number12
DOIs
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Reid, J. M., Qu, W., Safgren, S. L., Ames, M. M., Krailo, M. D., Seibel, N. L., Kuttesch, J., & Holcenberg, J. (2004). Phase I trial and pharmacokinetics of gemcitabine in children with advanced solid tumors. Journal of Clinical Oncology, 22(12), 2445-2451. https://doi.org/10.1200/JCO.2004.10.142