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


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Colin Watts1, Katharina Wanek2, Nicolas Counsell2, Paul Smith2
1University of Cambridge, Cambridge, UK, 2UCL Clinical Trials Unit, London, UK

Background

Objective: 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 prior to standard treatment with radiotherapy and temozolomide

Method

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 sites between August 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 in 6 eligible patients (10%): wound infections were reported in 5 patients (8%) and cerebrospinal fluid leakage in 3 patients (5%). One patient was not able to begin chemoRT (1/31, 3%), and 3 patients (3/31, 10%) were not able to begin chemoRT within 6 weeks of surgery, due to surgical complications.

After a median follow-up of 6.6 months, 36 patients (61%) are alive without progression, 8 patients (14%) are alive having progressed and 15 patients (25%) have died. Thirty patients (51%) have reported 61 adverse events of grade 3 or higher, the most common of which was muscle weakness reported in 5 patients (8%).

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 test efficacy of the combination.