Bevacizumab/Irinotecan. An active treatment for recurrent high grade gliomas: Preliminary results of an ANOCEF Multicenter Study

Rationale. - Second-line chemotherapy is disappointing in recurrent high-grade gliomas. Dramatic responses in recurrent high-grade gliomas have been reported in a recent monocentric trial with a novel association combining bevacizumab (anti-VEGF monoclonal antibody agent) and irinitecan. Objective. - To report the experience of the ANOCEF group (French speaking neuro-oncology association) using the bevacizumab-irinotecan combination in recurrent high-grade gliomas. Methods. - Eight centers were involved in this retrospective multicenter study. Bevacizumab-irinotecan was delivered as previously described in a compassional setting to non-selected patients suffering from a high-grade glioma (WHO grade III and IV). Response rate at two months of the onset of the treatment was analyzed using the Macdonald criteria. The toxicity profile of the treatment was also investigated. Results. - From 2006 to 2007, 77 patients were treated (median age: 52 years; median Karnofsky score: 70) for a recurrent high-grade glioma (49 grade IV, 28 grade III). At two months, the response rates were objective response = 36% (54% in grade III and 27% in grade IV); stable disease = 39%; progressive disease = 13%; patients not evaluable because of a rapid fatal clinical deterioration = 12%. Improvement was noted in 49% of patients. Among the main toxicities, we noted; intratumoral hemorrage (n = 5 with spontaneous regression in three) and thromboembolic complications including venous thrombophlebitis (n = 4), pulmonary embolism (n = 2), myocardial infarction (n = 1), grade III-IV hematotoxicity (n = 2), reversible leukoencephalopathy (n = 1). Conclusion. - This retrospective multicenter study adds further arguments in favor of the promising results of this new combination and its potential rapidity of action in recurrent high-grade gliomas. Antiangiogenic agents expose the patients to a well-known risk of thromboembolic and hemorragic complications, necessitating careful follow-up and patient selection in light of the cardiovascular contraindications. (C) 2008 Elsevier Masson SAS. Tous droits reserves.