Abstract
BACKGROUND: In the last years, few advances have been made improving progression-free survival and overall survival in patients with glioblastoma multiforme. There is no standard treatment for recurrent disease. We analyzed the feasibility of a multimodal strategy with second surgery plus carmustine wafers in the surgical cavity followed by intravenous fotemustine administration. METHODS: Retrospectively, we analyzed patients with recurrent glioblastoma treated with this multimodal strategy: carmustine wafers positioned during second surgery and subsequently, fotemustine drug as second-line treatment performed between 14 and 21 days after the second surgery. Intravenous fotemustine was administrated at 100mg/m2 every week for 3 consecutive weeks followed by a 5-week rest period; subsequently, an infusion every 3 weeks until progression disease or unacceptable toxicity or until a maximum of 12 cycles. During fotemustine therapy tumor response was evaluated by clinician assessment and by brain magnetic resonance imaging according to Macdonald criteria every two months or when clinically indicated. RESULTS: Twenty-four patients were analyzed. The median age was 53.6 years; all patients had KPS between 90 and 100, 19 patients (79%) performed a gross total resection >98% and 5 (21%) a gross total resection >90%. Seventeen patients were available for MGMT gene analysis and 10 (59%) patients had methylated MGMT gene promoter. The median time from first and second surgery was 17 months. The median progression-free survival from second surgery was 6 months (95% CI 3.9-8.05) and the median OS was 14 months (95% CI 11.1 - 16.8 months). No significant association was found between the resection rate (GTR >98% vs GTR >90%) and PFS (p = 0.4) and OS (p = 0.9). All patients were evaluable for toxicity which was predominantly haematological: 5 patients (21%) experienced grade 3-4 thrombocytopenia and 3 patients (12%) grade 3-4 leukopenia . Among non-haematological toxicity: 5 patients (21%) had grade 1-2 asthenia, 2 patients (8%) had grade 1-2 nausea/vomiting and 2 patients (8%) reported hypertransaminasemia. CONCLUSION: This multimodal strategy may be feasible in patients with recurrent glioblastoma; in particular, for patients in good clinical conditions