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Promising Early Results With Single-Agent Erlotinib in Recurrent Glioblastoma Multiforme

Promising Early Results With Single-Agent Erlotinib in Recurrent Glioblastoma Multiforme

CLEVELAND-Interim analysis of a phase II trial of erlotinib (Tarceva) for single-agent therapy for recurrent glioblastoma multiforme showed promising (although not durable) responses in about half of pa- tients, according to Michael A. Vogelbaum, MD, PhD, of the Cleveland Clinic Foundation (abstract 1558). The trial enrolled 31 patients with documented recurrent or progressive glioblastoma multiforme who had received previous radiation therapy and cytotoxic chemotherapy. No enzymeinducing antiepileptic agents were allowed. Patients were treated with 150 mg of erlotinib per day orally until tumor progression or study withdrawal. Tumor response was determined by magnetic resonance imaging, and tumor tissue samples were analyzed for epidermal growth factor receptor (EGFR) amplification. Six Partial Responses In an interim analysis of 27 of 31 patients, 6 patients had partial responses. One patient showed a partial response of his original tumor but then developed a separate unresponsive focus, and five have had disease stabilization for more than 3 months. Sixteen patients had tumor progression within 3 months of starting erlotinib. Six of the 11 patients with either partial response or stable disease later progressed and died. Median survival was 198.5 days, with a range of 55 to 360 days. Median overall survival of the entire cohort was 153 days, and median time to progression was 84 days. The median time to progression of the responders was 180 days. "The pattern of subsequent treatment failure in responders has suggested a diffuse spread of tumor (eg, gliomatosis cerebri or leptomeningeal spread). One patient had a tumorassociated cyst in which the steady state erlotinib level was determined and found to be approximately 40% of that observed in plasma." Approximately one-half of the tumors have had EGFR amplification, but EGFR amplification has not ensured a response to erlotinib, and responses have been observed in the absence of amplification. Encouraged by Responses "Although these results are preliminary in nature, we are encouraged by the response rate observed to date. The apparent lack of durability of response and the pattern of postresponse failure may be due, in part, to reduced drug penetration into the brain, to an inadequate dose, and/or to tumor heterogeneity," Dr. Vogelbaum concluded.

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