Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Evanthia GalanisNorth Central Cancer Treatment Group

Abstract

Temsirolimus (CCI-779) is a small-molecule inhibitor of the mammalian target of rapamycin (mTOR) and represents a rational therapeutic target against glioblastoma multiforme (GBM). Recurrent GBM patients with < or = 1 chemotherapy regimen for progressive disease were eligible. Temsirolimus was administered in a 250-mg intravenous dose weekly. Sixty-five patients were treated. The incidence of grade 3 or higher nonhematologic toxicity was 51%, and consisted mostly of hypercholesterolemia (11%), hypertriglyceridemia (8%), and hyperglycemia (8%). Grade 3 hematologic toxicity was observed in 11% of patients. Temsirolimus peak concentration (Cmax), and sirolimus Cmax and area under the concentration-time curve were decreased in patients receiving p450 enzyme-inducing anticonvulsants (EIACs) by 73%, 47%, and 50%, respectively, but were still within the therapeutic range of preclinical models. Twenty patients (36%) had evidence of improvement in neuroimaging, consisting of decrease in T2 signal abnormality +/- decrease in T1 gadolinium enhancement, on stable or reduced steroid doses. Progression-free survival at 6 months was 7.8% and median overall survival was 4.4 months. Median time to progression (TTP) for all patients was 2.3 mont...Continue Reading

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May 16, 2012·Cancer Discovery·Wolfgang WickMarkus Weiler
Feb 10, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Courtney A GranvillePhillip A Dennis
Jun 3, 2006·Cancer Research·Markus J RiemenschneiderDavid N Louis
Jul 5, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christopher E PelloskiKenneth D Aldape
Feb 1, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David A ReardonJohann de Bono
Sep 14, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Beatrice GiniPaul S Mischel
Oct 16, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·H Artee LuchmanSamuel Weiss
Feb 10, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David A ReardonJeremy N Rich
Oct 6, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Manuel HidalgoEric K Rowinsky
Jul 11, 2007·Molecular Cancer Therapeutics·Antonio M P OmuroEric Raymond
May 5, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wolfgang WickMonika E Hegi
Aug 18, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Inan OlmezBenjamin Purow
Mar 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Brian I Rini
Jun 11, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Valsamo K AnagnostouDavid L Rimm
Apr 5, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chee Khoon LeePaul de Souza
Jun 5, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert T Abraham, James J Gibbons
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Jan 16, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Patrick Y WenJordi Rodon
Jun 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Liu Hua WeiWolfgang A Weber
Feb 2, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Taofeek K OwonikokoFadlo Raja Khuri
Jul 12, 2011·Bulletin du cancer·Laetitia CoutteEric Raymond
Feb 3, 2021·NPJ Genomic Medicine·Fawz S AlHarthiMalak Abedalthagafi

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