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

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Abstract
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 O6‐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. © 2003 American Cancer Society. DOI 10.1002/cncr.11305