DGI-017 Bevacizumab Plus Irinotecan in Malignant Gliomas

Background Malignant gliomas (MG) comprise the most common types of primary central nervous system tumours. Purpose An observational study to evaluate the efficacy and safety of bevacizumab plus irinotecan used off-label in recurrent malignant gliomas. Materials and Methods Pharmacy records were reviewed to identify patients with histologically proven MG who had been treated with bevacizumab plus irinotecan as second- or third-line chemotherapy. Eligible patients: radiological evidence of tumour recurrence or progression prior to initiation of chemotherapy and STUPP regimen as first line. Patients were treated with IV bevacizumab (10 mg/kg) on days 1, 15 and 29 every 6 weeks and IV irinotecan (340 mg/m² if concomitant enzyme-inducing antiepileptic drugs (EIAEDs) or 125 mg/m 2 if no EIAEDs) on days 1, 15 and 29 every 6 weeks. Treatment was continued until disease progression or unacceptable toxicity. Tumours were evaluated by brain MRIs. Response to treatment was assessed at baseline and every 3 cycles or whenever progression was clinically suspected. The Macdonald criteria were used to evaluate the response. Toxicity was assessed before each cycle by medical history, haematology and biochemistry. Adverse events were graded according to NCI-CTCAEv4. Antiepileptics were administered as medically indicated. Results Seven patients (5 men, 2 women) were evaluated. Mean age was 52.4 years and glioblastoma multiforme (GBM) was the major histotype (71%). 71.4% of patients had had a total resection as primary surgery and 14.3% of patients had undergone second surgery at disease recurrence. The median number of cycles administered was 4. Overall activity comprised 3 partial responses (42.86%); and 1 (14.28%) disease stabilisation for a Disease Control Rate of 57.14%. Three patients (42.86%) experienced disease progression. The median progression-free survival was 8.2 months (95% confidence interval (CI): 5.4–10.9) and the median overall survival was 11.8 months (95% CI: 6.1–17.5). No central nervous system haemorrhages occurred, but one patient developed deep venous thromboses. Conclusions The combination of bevacizumab and irinotecan seems to run as an alternative and active regimen for recurrent MG with acceptable toxicity but it is necessary to expand the study population to draw definitive conclusions. No conflict of interest.