Motexafin gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: A Children's Oncology Group phase i study

Kristin A. Bradley, Ian F. Pollack, Joel M. Reid, Peter C. Adamson, Matthew M. Ames, Gilbert Vezina, Susan Blaney, Percy Ivy, Tianni Zhou, Mark Krailo, Gregory Reaman, Minesh P. Mehta

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

The purpose of this study was to determine the dose-limiting toxicities, maximum tolerated dose, pharmacokinetics, and intratumor and brain distribution of motexafin gadolinium (MGd) with involved field radiation therapy in children with newly diagnosed intrinsic pontine gliomas. MGd was administered as a 5-min intravenous bolus 2-5 h prior to standard radiation. The starting dose was 1.7 mg/kg. After first establishing that 5 doses/week for 6 weeks was tolerable, the dose of MGd was escalated until dose-limiting toxicity was reached. Radiation therapy was administered to 54 Gy in 30 once-daily fractions. Forty-four children received MGd at doses of 1.7 to 9.2 mg/kg daily prior to radiation therapy for 6 weeks. The maximum tolerated dose was 4.4 mg/kg. The primary dose-limiting toxicities were grade 3 and 4 hypertension and elevations in serum transaminases. Median elimination half-life and clearance values were 6.6 h and 25.4 ml/kg/h, respectively. The estimated median survival was 313 days (95% confidence interval, 248-389 days). The maximum tolerated dose of MGd and the recommended phase II dose was 4.4 mg/kg when administered as a daily intravenous bolus in conjunction with 6 weeks of involved field radiation therapy for pediatric intrinsic pontine gliomas.

Original languageEnglish (US)
Pages (from-to)752-758
Number of pages7
JournalNeuro-oncology
Volume10
Issue number5
DOIs
StatePublished - Oct 1 2008

Keywords

  • Motexafin gadolinium
  • Pontine glioma
  • Radiation therapy

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Bradley, K. A., Pollack, I. F., Reid, J. M., Adamson, P. C., Ames, M. M., Vezina, G., Blaney, S., Ivy, P., Zhou, T., Krailo, M., Reaman, G., & Mehta, M. P. (2008). Motexafin gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: A Children's Oncology Group phase i study. Neuro-oncology, 10(5), 752-758. https://doi.org/10.1215/15228517-2008-043