Is it time to reconsider the role of irinotecan for the treatment of high-grade gliomas?

Irinotecan is a topoisomerase 1 inhibitor that is converted to the active metabolite SN-38 by carboxylesterase.¹ Based on preclinical data showing that irinotecan had activity against gliomas, and the assumption that irinotecan crossed the blood–brain barrier (BBB), a single arm phase II study was conducted in 60 patients with recurrent high-grade gliomas (HGGs).² This study used an irinotecan dose of 125 mg/m² once weekly for 4 weeks followed by a 2-week rest, and reported a partial response rate of 15%, with 55% of patients having stable disease for at least 12 weeks. These results suggested that irinotecan had activity in this patient population and led to the adoption of this agent for treatment of recurrent HGG.

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