2027 Background: Bevacizumab has shown activity in recurrent glioblastoma (GBM), and few data are available on the combination of bevacizumab and nitrosoureas, that represent the standard cytotoxic option. Fotemustine (FTM) is a nitrosourea with elevated lipophilic properties.
METHODS
In this phase II study patients with GBM recurrent after surgery, radiation therapy, and concomitant/adjuvant temozolomide were elegible. The treatment consisted of an induction phase with BV at 10 mg/kg intravenously on day 1 and 15 and fotemustine (FTM) at 75mg/m2intravenously on day 1 and 8, followed after 3 week interval by a maintenance phase with BV at 10 mg/kg i.v. and FTM 75mg/ m2 every 3 weeks until tumor progression or unacceptable toxicity. Patients had undergone clinical and MRI assessment 1 month after the start of treatment and thereafter every 2 months. The primary endpoint was progression-free survival at 6 months (PFS6), whereas secondary endpoints were response rate (RR), based on RANO criteria, progression-free (PFS) and overall survival (OS), and safety.
RESULTS
From April 2008 until November 2010, 54 patients (males 35, females 19, median age 57) were enrolled. PFS6, PFS12 and mPFS were 44%, 21% and 5.29 months respectively. mOS was 9.13 months with 77.4% and 31% of patients surviving at 6 and 12 months respectively. Response rates were as follows: 2CR (4%), 24 PR (44%), 22 SD (41%) and 6 PD (11%). A significant neurological improvement was observed in 57 % of patients, being steroids reduced or interrupted in 64%. 44/54 (81%) patients have progressed and patterns of progression were local in 29/44 (66%), multicentric 10/44 (23%), gliomatosis 3/44 (6%) and isolated leptomeningeal spread 2/44 (5%). 12/54 (22%) patients with grade 3/4 piastrinopenia/leukopenia discontinued fotemustine, whereas 4/54 (7.4%)discontinued bevacizumab (1 stroke, 1 intratumoral haemorrhage, 1 GI perforation and 1 pulmonary embolism).
CONCLUSIONS
Combination of bevacizumab and fotemustine in glioblastomas recurrent after standard radiotherapy + temozolomide is safe and promising. The analysis of MGMT methylation status is ongoing.