Journal article
The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: A phase 1 dose-escalation trial
SK Sandhu, WR Schelman, G Wilding, V Moreno, RD Baird, S Miranda, L Hylands, R Riisnaes, M Forster, A Omlin, N Kreischer, K Thway, H Gevensleben, L Sun, J Loughney, M Chatterjee, C Toniatti, CL Carpenter, R Iannone, SB Kaye Show all
Lancet Oncology | ELSEVIER SCIENCE INC | Published : 2013
Abstract
Background: Poly(ADP-ribose) polymerase (PARP) is implicated in DNA repair and transcription regulation. Niraparib (MK4827) is an oral potent, selective PARP-1 and PARP-2 inhibitor that induces synthetic lethality in preclinical tumour models with loss of BRCA and PTEN function. We investigated the safety, tolerability, maximum tolerated dose, pharmacokinetic and pharmacodynamic profiles, and preliminary antitumour activity of niraparib. Methods: In a phase 1 dose-escalation study, we enrolled patients with advanced solid tumours at one site in the UK and two sites in the USA. Eligible patients were aged at least 18 years; had a life expectancy of at least 12 weeks; had an Eastern Cooperativ..
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Awarded by National Cancer Institute
Funding Acknowledgements
This trial was funded by Merck Sharp and Dohme, a subsidiary of Merck. SKS was awarded the 2010 ASCO Annual Meeting Merit Award by the ASCO Conquer Cancer Foundation for presentation of parts of this work. SM was funded by the Prostate Cancer Foundation. The Drug Development Unit of the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research is supported in part by a programme grant from Cancer Research UK. Support to the Institute of Cancer Research was also provided by the Experimental Cancer Medicine Centre. We also acknowledge support from Prostate Cancer UK.