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

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. © 2003 American Cancer Society. DOI 10.1002/cncr.11305