To assess the efficacy and safety of alternative fotemustine administration schedule in elderly patients with recurrent glioblastoma. Patients aged >65 years with recurrent glioblastoma received fotemustine (80 mg/m; days 1, 15, 30, 45 and 60, and subsequently every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months. Main secondary end point was safety. 58 patients were enrolled at two centers. PFS at 6 months was 47% (27 patients) and overall response rate was 29%. Median PFS and survival were 6 and 7 months, respectively, and longer in responders versus nonresponders. No grade 3-4 hematological toxicities occurred. The alternative fotemustine administration schedule was an effective and safe treatment for recurrent glioblastoma in elderly patients.