Phase II Study of Bevacizumab Plus Irinotecan in Patients with Recurrent High-Grade Gliomas
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- Category: Vol. 78, December 2010
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Phase II Study of Bevacizumab Plus Irinotecan in Patients with Recurrent High-Grade Gliomas,SOHAIR ISMAIL, EMAN EL-SHEIKH, DALIA ABD EL-GHANY and ASHRAF AL-ABYAD
Abstract
Aim of the Study: This prospective phase II study was conducted to determine if the combination of a novel antian-giogenic therapy, bevacizumab, and a cytotoxic agent, irino-tecan, is effective and safe for patients with recurrent high-grade gliomas.
Patients and Methods: Patients with recurrent high-grade gliomas were treated with bevacizumab 1 0mg/kg in combina-tion with irinotecan. Patients taking enzyme-inducing antie-pileptic drugs (EIAED) received irinotecan 340mg/m2, whereas patients not taking EIAED received 125mg/m2 i.v. The com-bination were given every 2 weeks until the occurrence of grade 3/4 toxicity or tumor progression. Tumor response and toxicity were assessed.
Results: The present study included 23 patients with recurrent high-grade gliomas (13 patients had grade IV glioma, and 10 patients had grade III glioma). The study was carried out in the Clinical Oncology Department, Ain-Shams Univer-sity Specialized Hospital between February 2009 to August 2010. There were 15 males and 8 females, the median age was 44 years (range 26-62 years), with a median karnofsky performance status (KPS) of 80%. All patients had undergone prior surgical resection with radia tion therapy and temozo-lomide. Out of the 23 patients, 11 patients (47.8%) achieved an objective response (partial response). All objective responses were evident on the first radiologic evaluation performed after the 4 initial treatments. Five patients (21.7%) had stable dis-ease and 7 patients (30.4%) had disease progression. The patients who responded were able to taper their steroids and improved neurologically. The 6-month progression free sur-vival (PFS) rate was 64.9% (CI: 44%-85.8%) and at 12 month was 58.4% (CI: 34.3%-82.6%). The 6-month overall survival (OS) rate was 65.2% (CI: 45.8%-84.7%) and at 12 month was 60.9% (CI: 38.3%-83.4%). When survival was analyzed accor-ding to the different prognostic factors, it was found that responders showed significantly better OS and PFS (p=0.032, 0.036 respectively). The 23 patients received 4-16 doses of treatment (median 8). Overall, patients tolerated treatment well. None of the patients discontinued treatment or had dose reduction because of side effects or poor compliance. Impor-tantly, we did not observe any thrombotic complications or severe bleeding other than epistaxis in 2 patients (8.6%). There were no grade 3/4 hematologic toxicities. Grade 3 non-hematologic toxicities included; 3 cases (13%) of fatigue and another 2 cases (8.6%) of hypertension.
Conclusions: The combination of bevacizumab and irino-tecan is an active regimen for recurrent grade III-IVglioma with acceptable toxicity.