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

Al Musella's Comments: (This is his personal views and are not necessarily the views of the Musella Foundation!)


Posted on: 04/29/2003

1: Cancer 2003 May 1;97(9 Suppl):2359-62 Related Articles, Links

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

Friedman HS, Keir ST, Houghton PJ.

Department of Surgery, Duke University Medical Center, Durham, North Carolina.

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.

Cancer 2003;97(9 Suppl):2359-62. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11305

PMID: 12712457 [PubMed - in process]

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