The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors.

Journal Article (Review)

Irinotecan is a water-soluble derivative of camptothecin, an alkylator originally extracted from the Chinese tree Camptotheca acuminata. Laboratory studies have demonstrated the activity of irinotecan in a broad panel of pediatric and adult central nervous system tumor xenografts in athymic nude mice. These studies led to a Phase II trial that confirmed the activity of this agent in the treatment of recurrent malignant glioma. Subsequent laboratory studies have demonstrated that a combination of irinotecan (CPT-11) and alkylating agents, particularly 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), increases antitumor effects to a level well above the additive effects of the individual agents. These laboratory studies generated a recently completed Phase I trial of CPT-11 + BCNU, which now is being evaluated in a formal Phase II trial for adults with newly diagnosed or recurrent malignant glioma. More recent studies have demonstrated similar interaction between CPT-11 and temozolomide and have led to a Phase I trial of these agents in the treatment of adults with malignant glioma. Studies currently are addressing the role of O(6)-alkylguanine-DNA alkyltransferase (AGT) in reducing the benefits of combining CPT-11 with temozolomide and the potential therapeutic gain from utilizing an inhibitor of AGT.

Full Text

Duke Authors

Cited Authors

  • Friedman, HS; Keir, ST; Houghton, PJ

Published Date

  • May 1, 2003

Published In

Volume / Issue

  • 97 / 9 Suppl

Start / End Page

  • 2359 - 2362

PubMed ID

  • 12712457

International Standard Serial Number (ISSN)

  • 0008-543X

Digital Object Identifier (DOI)

  • 10.1002/cncr.11305

Language

  • eng

Conference Location

  • United States