Phase I trial and pharmacokinetic study of raltitrexed in children with recurrent or refractory leukemia: A pediatric oncology group study

Terzah M. Horton, Susan M. Blaney, Anne Marie Langevin, John Kuhn, Barton Kamen, Stacey L. Berg, Mark Bernstein, Steven Weitman

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Purpose: To evaluate the toxicity, antileukemic activity, and pharmacology of raltitrexed administered weekly for 3 weeks to patients with refractory or recurrent leukemia. Experimental Design: Raltitrexed was administered as a 15-minute infusion for 3 consecutive weeks every 5 weeks, at doses ranging from 1.3 to 2.8 mg/m2. The first course was used to determine the dose-limiting toxicities and maximum tolerated dose. Correlative studies included an assessment of raltitrexed pharmacokinetics and measurement of plasma 2′-deoxyuridine concentrations, a surrogate measure of thymidylate synthase inhibition. Results: Twenty-one children (18 evaluable) with refractory leukemia received 25 courses of raltitrexed. The dose-limiting toxicity was reversible elevation in liver transaminases at the 2.8-mg/m2 dose level and the maximum tolerated dose was 2.1 mg/m2 per dose. Pharmacokinetics were best characterized by a two-compartment model with a clearance of 139 mL/min/m2 (8.3 L/h/m2), a 2.4-L volume of distribution, an initial half-life (t1/2α) of 6 minutes, and a terminal half-life (t1/2β) of 45 minutes. There were three objective responses. Conclusions: Raltitrexed was well tolerated when administered as a single agent to children with recurrent or refractory leukemia. We observed preliminary evidence of antileukemia activity using this weekly dosing schedule and these observations support further evaluation of raltitrexed in this population.

Original languageEnglish (US)
Pages (from-to)1884-1889
Number of pages6
JournalClinical Cancer Research
Volume11
Issue number5
DOIs
StatePublished - Mar 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Phase I trial and pharmacokinetic study of raltitrexed in children with recurrent or refractory leukemia: A pediatric oncology group study'. Together they form a unique fingerprint.

Cite this