PO45A SYSTEMATIC REVIEW STRATEGY IDENTIFIES CHEMOTHERAPEUTIC CANDIDATES FOR EFFICACIOUS INTRA-CRANIAL DELIVERY IN GLIOBLASTOMA

Abstract

INTRODUCTION: Surgically delivering chemotherapy to a resection cavity offers hope in targeting residual glioblastoma cells responsible for tumour recurrence. We conducted a systematic review of 311 agents combining scientific literature, clinical trial databases and chemical structure directories, to identify candidates suitable to repurpose for localised glioblastoma drug delivery. METHOD: All known anti-neoplastic drugs from Martindale's Online Drug Library were systematically reviewed. Martindale, the British National Formulary, OvidSP, and ChemSpider were used to assess neurotoxicity, efficacy, and Blood Brain Barrier (BBB) penetration to generate inclusion/exclusion criteria: criterion 1 excluded neurotoxic agents, but included those associated with systemic side-effects; criterion 2 included efficacious agents in vitro; criterion 3 included agents with no/low in vivo or Phase II/III clinical efficacy; criterion 4 included agents with observed/predicted lack of, or poor BBB penetration. RESULTS: Seventy-seven drugs were excluded due to neurotoxicity, 107 excluded due to poor in vitro efficacy and 68 excluded due to lack of in vivo or clinical efficacy despite good/moderate BBB penetration. Of the remaining 59 drugs, 13 were recommended as good candidates, where lack of in vivo or clinical efficacy may be due to poor BBB penetration. Candidates included carmustine (already delivered as Gliadel), demonstrating proof-of-concept of our review strategy, cilengitide, irinotecan, bevacizumab diaziquone, docetaxel and trabedersen. CONCLUSION: Localised drug delivery candidates were identified using a systematic review strategy which may be applied in the evaluation of future novel experimental or repurposed agents.