Olaparib penetrates glioblastoma at therapeutic levels: results of stage 1 of the OPARATIC trial; a phase I study of olaparib in combination with temozolomide in patients with relapsed glioblastoma


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Anthony Chalmers1, Alan Jackson2, Helen Swaisland3, William Stewart4, Sarah Halford5, Rhoda Molife6, Darren Hargrave7, Alex McCormick3
1University of Glasgow, Glasgow, UK,2University of Manchester, Manchester, UK,3AstraZeneca Ltd, Macclesfield, UK,4NHS Greater Glasgow & Clyde, Glasgow, UK,5Cancer Research UK Drug Development Office, London, UK,6Royal Marsden Hospital, London, UK,7Great Ormond Street Hospital, London, UK

Abstract

Background

Drug delivery is a major problem in the treatment of glioblastoma (GBM). Tumour pharmacokinetics (PK) of small molecule targeted agents have not been widely studied in GBM, and poor activity may result either from lack of biological efficacy or from adverse PK. Olaparib, a small molecule inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP), has potential to overcome treatment resistance of GBM [1]. Despite radiological responses in brain metastases [2], GBM penetration by olaparib has not been studied.