Bevacizumab and irinotecan in recurrent malignant glioma, a single institution experience

Abstract

Background: Treatment options of recurrent malignant glioma are very limited and with a poor survival benefit. Malignant gliomas are highly vascular tumors and represent potentially promising target for anti-vascular endothelial growth factor therapies. Results from phase II trials suggest that the combination of bevacizumab and irinotecan is beneficial to patients.

Material and methods: We retrospectively reviewed medical documentation of 19 patients with recurrent malignant gliomas treated with bevacizumab and irinotecan. All patients received bevacizumab at 10mg/kg in combination with irinotecan 340mg/m² or 125mg/m² (with or without concomitant enzyme inducing antiepileptic drugs, respectively) every two weeks. Patient clinical characteristics, drug toxicities, response rate, progression free survival (PFS) and overall survival (OS) were evaluated.

Results: We treated 14 (73.7%) man and 5 (26.3%) women. Mean age was 44.7 years (range 27-74). Thirteen patients had glioblastoma multiforme, 5 anaplastic astrocitoma and 1 anaplastic oligoastrocytoma. As an initial therapy all had a standard therapy with primary resection followed by postoperative chemoradiotherapy, except one. WHO performance status range 0-2. In our group average number of chemotherapy applications was 9.3 (range 1-17). Radiological response after 3 months was observed in 9 patients (1 complete response, 8 partial response), seven patients had stable disease and three patients have progressed. The median progression free survival interval was 6.8 months (95%CI: 5.3-8.3); 6 months PFS rate was 52.6%. The median overall survival was 7.7 months (95%CI: 6.6-8.7). Six-month survival rate and twelve-month survival rate were 68.4% and 31.6% respectivelly. There were 16 cases of haematopoetic toxicity, all G1-2. Non-haematopoetic toxicity was present in 14 cases, all G1-2, except one patient with proteinuria G3. No grade 4 toxicities, no trombembolic event and no intracranial hemorrhage were observed.

Conclusion: The combination of bevacizumab and irinotecan is an active regimen with acceptable toxicity in malignant glioma patients. Comparison of progression free survival and survival rates with historical data indicate a trend to better survival, still randomized controlled trials are needed to confirm any survival benefit.