Role of temozolomide in pediatric brain tumors

Palma Maurizi, Gianpiero Tamburrini, Giuseppe Barone, Riccardo Riccardi

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

FEATURES OF TEMOZOLOMIDE: Temozolomide (TMZ) belongs to the imidazotetrazine class and it is a DNA-methylating agent that has a good antitumor activity. Despite of dacarbazine, TMZ is spontaneously converted into its active metabolite 5-(3-methyltriazen-l-yl)imidazole-4-carboxamide at physiologic pH, so it is not required in enzymatic demethylation in the liver. TMZ is able to cross the blood brain barrier and is stable at gastric acid pH so it has almost 100% oral bioavailability and is rapidly absorbed after it is taken orally. TEMOZOLOMIDE IN CANCER PATIENTS: On the basis of the relatively safe toxicity and the findings achieved in adult malignant gliomas, phase I and II clinical trials were set up to evaluate the opportunity of using this novel drug in pediatric cancer, too. In this review, we evaluate the antitumor activity of TMZ against high-grade gliomas, low-grade-gliomas, and medulloblastoma/primitive neuroectodermal tumors analyzing several phases I and II clinical trials in children. CONCLUSIONS: In spite of the poor activity of TMZ against pediatric brain tumors, the use of the drug in combination with other compounds should be evaluated in phases I and II clinical trials. Moreover, the evaluation of the methylation status of the O6-methylguanine DNA methyltransferase promoter in glioblastoma biopsy specimens could be assayed as a predictive factor of TMZ efficacy.
Original languageEnglish
Pages (from-to)652-661
Number of pages10
JournalCHILDS NERVOUS SYSTEM
Volume22
DOIs
Publication statusPublished - 2006

Keywords

  • child tumors
  • temozolomide

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