Phase I study of gemcitabine (difluorodeoxycytidine) in children with relapsed on refractory leukemia (CCG-0955): A report from the children's cancer group

P. G. Steinherz, N. L. Seibel, M. M. Ames, V. I. Avramis, M. D. Krailo, W. Liu-Mares, J. M. Reid, S. L. Safgren, G. H. Reaman

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21 Scopus citations


To determine the maximum tolerated dose (MTD) and assess the toxicity profile and pharmacokinetics of weekly gemcitabine infusions in pediatric patients with refractory hematologic malignancies. Fourteen patients under 21 years old were given infusions of gemcitabine for escalating durations at 10 mg/m 2/min weekly for three consecutive weeks. Two males and two females were studied at each dose level. Pharmacokinetics of the drug's metabolism were measured by high pressure-liquid chromatography (HPLC) for 24h after the first dose. Intracellular difluorodeoxycytidine triphosphate formation in leukemic blasts was measured in selected patients. The MTD of gemcitabine in these patients was 3600 mg/m 2/week for three consecutive weeks (10mg/m 2/min for 360 min). Hepatotoxicity was the dose limiting toxicity. Thirty to fifty percent of patients exhibited fever, rash, or myalgia. Rare instances of hypotension and pulmonary toxicity were observed. Two of six patients [one acute lymphoblastic leukemia (ALL) and one acute myelogenous leukemia (AML)] treated at the MTD had at least M 2 marrows, although peripheral blood counts did not recover sufficiently for the patients to be considered in complete response. Pharmacokinetics of gemcitabine fit a two-compartment open model with terminal half-life and plasma clearance value of 62 min and 2.21/min/m 2, respectively. No gender differences were observed. In conclusion, the MTD of gemcitabine was 10mg/m 2/min for 360 min every week for 3 weeks. This is the recommended phase II dose schedule for children with leukemia. The activity of the drug at this schedule in heavily pretreated, refractory patients warrants a phase II trial in hematologic malignancies.

Original languageEnglish (US)
Pages (from-to)1945-1950
Number of pages6
JournalLeukemia and Lymphoma
Issue number10
StatePublished - Oct 2002


  • Children's cancer group
  • Gemcitabine
  • HPCL
  • Relapsed or refractory leukemia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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