O5.04 * preliminary results of the gala-5 study: an evaluation of the tolerability and feasibility of combining 5-amino-levulinic acid (5-ala) with carmustine wafers (gliadel) in the surgical management of primary glioblastoma

BACKGROUND: Fluorescence-guided resection of glioblastoma improves surgical cytoreduction. Intra-operative carmustine wafers may enhance survival in patients with good surgical resection. The objective of this study was to establish the safety and tolerability of combining fluorescence-guided surgical resection (5-ALA) with intra–operative chemotherapy (carmustine wafers) in patients with primary glioblastoma (GBM) prior to standard treatment with radiotherapy and temozolomide. METHODS: A single arm design with the following inclusion criteria: • Age 18+ years • Patient reviewed at a specialist neuro-oncology MDT • Imaging evaluated by a neuro-radiologist and judged to be a GBM • Radical resection judged to be realistic by the neurosurgeons (i.e. NICE criteria for the use of Carmustine wafers can be met) • WHO performance status 0 or 1 on clinical review. RESULTS: Seventy-two patients were recruited from 8 UK sites between July 2011 and May 2013; 64 patients received carmustine wafer implants and 59 patients were found to be eligible after surgery. Thirteen patients were found to be ineligible due to: wafers not inserted (n = 8); GBM not diagnosed post-operatively (n = 4); simultaneous diagnosis of unrelated cutaneous sebaceous carcinoma (n = 1). There were 8 surgical complications reported in 6 patients: wound infections were reported in 5 patients (8%) and cerebrospinal fluid leakage in 3 patients (5%). One patient was not able to begin chemoRT (1/33, 3%), and 4 patients (4/33, 12%) were not able to begin chemoRT within 6 weeks of surgery, due to surgical complications. After a median follow-up of 10.8 months, 25 patients (42%) are alive without progression, 16 patients (27%) are alive having progressed and 18 patients (31%) have died. Thirty-three patients (56%) have reported 68 adverse events of grade 3 or higher, 5 of these were reported as being ‘possibly’ related to the combination of 5-ALA and carmustine wafers: sepsis (n = 2), wound infection (n = 2), seizure (n = 1). CONCLUSION: The combination of 5-ALA and carmustine wafers is safe and tolerable in the surgical management of primary glioblastoma. A phase III randomised controlled trial is being designed to evaluate efficacy.