Abstract
Ganetespib, a highly potent, small-molecule Heatshock protein 90 inhibitor, has potential efficacy in malignant pleural mesothelioma (MPM) via activity on critical survival pathways and known synergies with antifolates and platinum chemotherapy. We conducted a dose-escalation study to identify the maximum tolerated dose (MTD) of ganetespib in patients with chemotherapy-naïve MPM. MESO-02 (ClinicalTrials.gov: NCT01590160) was a nonrandomized, multicenter, phase Ib trial of 3-weekly ganetespib (100 mg/m2, 150 mg/m2, 200 mg/m2; days 1 and 15) with pemetrexed (500 mg/m2; day 1) and cisplatin (75 mg/m2; day 1) or carboplatin (area under concentration-time curve 5; day 1) in patients with MPM. Dose escalation was performed using the 3 + 3 design (cisplatin) and accelerated titration design (carboplatin). Secondary endpoints included best response, progression-free survival (PFS), and pharmacogenomic analyses. Of 27 patients enrolled (cisplatin, n = 16; carboplatin, n = 11), 3 experienced dose-limiting toxicities: grade 3 nausea (cisplatin, n = 1; carboplatin, n = 1) and grade 2 infusion-related reaction (carboplatin, n = 1). Ganetespib's MTD was 200 mg/m2. Partial response was observed in 14 of 27 patients (52%; 61% in 23 response-ev...Continue Reading
References
Jul 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nicholas J VogelzangPaolo Paoletti
Feb 5, 2004·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M J Byrne, A K Nowak
Dec 31, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Dean A FennellRobin Rudd
Sep 30, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jan P van MeerbeeckUNKNOWN National Cancer Institute of Canada
Dec 19, 2006·Molecular Cancer Therapeutics·Ju-Hee LeeYung-Jue Bang
Jul 3, 2008·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Armando SantoroChristian Manegold
Nov 1, 2008·International Journal of Cancer. Journal International Du Cancer·Sergey V IvanovHarvey I Pass
Feb 24, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Luisella RighiGiovanni Selvaggi
Jan 20, 2011·Neoplasia : an International Journal for Oncology Research·Wen-Bin OuJonathan A Fletcher
Jan 26, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Paolo Andrea ZucaliArmando Santoro
Jan 31, 2012·Nature·Guangbo ChenRong Li
Aug 8, 2012·Proceedings of the National Academy of Sciences of the United States of America·Shane R SteckleinRoy A Jensen
Mar 28, 2013·BMC Cancer·Jonathan W GoldmanLee S Rosen
Apr 16, 2013·The Lancet Oncology·Wieneke A BuikhuisenPaul Baas
Dec 18, 2013·Cell Death & Disease·J-L RohJ Y Park
Feb 22, 2014·Cancer Research·David A Proia, Richard C Bates
Nov 27, 2014·Nature Communications·Qingming FangRobert W Sobol
Mar 25, 2015·The Lancet Oncology·Lee M KrugPaul Baas
Jun 23, 2015·Oncogene·S BusaccaD A Fennell
Jan 1, 2016·Lancet·Gérard ZalcmanUNKNOWN French Cooperative Thoracic Intergroup (IFCT)
Feb 6, 2016·International Journal of Oncology·Amr S Abu LilaTatsuhiro Ishida
Jul 14, 2016·Journal of the National Comprehensive Cancer Network : JNCCN·David S EttingerMiranda Hughes
Feb 25, 2017·Nature Communications·Atul BhardwajFrank Wuest
Jul 22, 2017·The Lancet Oncology·Michele MaioHedy L Kindler
Sep 4, 2017·Occupational and Environmental Medicine·Chimed-Ochir OdgerelJukka Takala
Feb 6, 2018·Annual Review of Cancer Biology·Devon M FitzgeraldSusan M Rosenberg
May 14, 2018·The Lancet Oncology·Vanesa GregorcMary O'Brien