Phase I study of O6-benzylguanine and temozolomide administered daily for 5 days to pediatric patients with solid tumors

Katherine E. Warren, Alberta A. Aikin, Madeleine Libucha, Brigitte C. Widemann, Elizabeth Fox, Roger J. Packer, Frank M. Balis

Research output: Contribution to journalArticle

Abstract

Purpose: This pediatric phase I trial of O6-benzylguanine (O6BG) and temozolomide (TMZ) on a daily schedule for 5 days, every 28 days was performed to determine the maximum-tolerated dose of TMZ when given with a biologically active dose of O6BG and to define the toxicity profile of the combination in children with solid tumors. Patients and Methods: Patients ≤ 21 years old with refractory solid tumors were eligible. O 6BG was administered intravenously over 60 minutes daily for 5 days. TMZ was administered orally 30 minutes after completion of each O6BG infusion. Starting doses of O6BG and TMZ were 60 mg/m2/d and 28 mg/m2/d, respectively. O6BG was escalated to 90 and 120 mg/m2/d; TMZ was subsequently escalated to 40, 55, 75, and 100 mg/m2/d. Cycles were repeated every 28 days. Results: Forty-one patients were enrolled; 32 patients were assessable for toxicity. The combination of O6BG and TMZ was tolerable at TMZ doses less than half of the conventional dose of 200 mg/m2/d. Myelosuppression occurred sporadically at all dose levels and was the dose-limiting toxicity (DLT) at 100 mg/m2/d of TMZ combined with 120 mg/m2/d O6BG. Nonhematologic toxicities were generally mild. Evidence of antitumor activity was observed at 120 mg/m2/d O6BG combined with TMZ doses of 55 mg/m2/d and above. Conclusion: The recommended doses of O 6BG administered with TMZ on a 5-day schedule in children are 120 mg/m2/d of O6BG and 75 mg/m2/d of TMZ. Evidence of activity was observed at these doses. Myelosuppression was the DLT.

Original languageEnglish (US)
Pages (from-to)7646-7653
Number of pages8
JournalJournal of Clinical Oncology
Volume23
Issue number30
DOIs
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Warren, K. E., Aikin, A. A., Libucha, M., Widemann, B. C., Fox, E., Packer, R. J., & Balis, F. M. (2005). Phase I study of O6-benzylguanine and temozolomide administered daily for 5 days to pediatric patients with solid tumors. Journal of Clinical Oncology, 23(30), 7646-7653. https://doi.org/10.1200/JCO.2005.02.0024