Irinotecan: promising activity in the treatment of malignant glioma

Patients with malignant glioma continue to have a dismal outcome. Those with glioblastoma multiforme, the most common type of malignant glioma, have a median survival of 40 to 60 weeks following diagnosis and only 16 to 24 weeks after recurrence. While standard therapy is surgery and external-beam radiotherapy, data indicate that chemotherapy improves the clinical outcome of some patients. Irinotecan (CPT-11, Camptosar) possesses significant activity against malignant glioma, and potentiation of this activity with combination partners, including the alkylator 1,2-bis(2-chloroethyl)-1-nitrosourea (carmustine, BCNU), is being evaluated in an ongoing phase II study. Also, the combination of irinotecan plus temozolomide (Temodar) has produced synergism in preclinical studies as well as encouraging responses in ongoing clinical trials. Other investigative directions include studies of irinotecan plus temozolomide and O6-benzylguanine (O6-BG) to assess the ability of O6-BG to maximize the therapeutic benefits of irinotecan combined with temozolomide.