Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme Journal Article


Authors: Chang, S. M.; Wen, P.; Cloughesy, T.; Greenberg, H.; Schiff, D.; Conrad, C.; Fink, K.; Robins, H. I.; De Angelis, L.; Raizer, J.; Hess, K.; Aldape, K.; Lamborn, K. R.; Kuhn, J.; Dancey, J.; Prados, M. D.
Article Title: Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme
Abstract: Purpose: Loss of PTEN, which is common in glioblastoma multiforme (GBM), results in activation of the mammalian target of rapapmycin (mTOR), thereby increasing mRNA translation of a number of key proteins required for cell-cycle progression. CCI-779 is an inhibitor of mTOR. The primary objectives of this study were to determine the efficacy of CCI-779 in patients with recurrent GBM and to further assess the toxicity of the drug. Experimental Design: CCI-779 was administered weekly at a dose of 250 mg intravenously for patients on enzyme-inducing anti-epileptic drugs (EIAEDs). Patients not on EIAEDs were initially treated at 250 mg; however, the dose was reduced to 170 mg because of intolerable side effects. Treatment was continued until unacceptable toxicity, tumor progression, or patient withdrawal. The primary endpoint was 6-month progression-free survival. Results: Forty-three patients were enrolled; 29 were not on EIAEDs. The expected toxicity profile of increased lipids, lymphopenia, and stomatitis was seen. There were no grade IV hematological toxicities and no toxic deaths. One patient was progression free at 6 months. Of the patients assessable for response, there were 2 partial responses and 20 with stabilization of disease. The median time to progression was 9 weeks. Conclusions: CCI-779 was well tolerated at this dose schedule; however, there was no evidence of efficacy in patients with recurrent GBM. Despite initial disease stabilization in approximately 50% of patients, the durability of response was short. Because of the low toxicity profile, CCI-779 may merit exploration in combination with other modalities. © 2005 Springer Science + Business Media, Inc.
Keywords: adult; cancer chemotherapy; cancer survival; clinical article; controlled study; treatment outcome; aged; disease-free survival; middle aged; clinical trial; disease course; drug tolerability; dose response; drug dose reduction; drug efficacy; antineoplastic agents; chemotherapy; brain neoplasms; controlled clinical trial; phase 2 clinical trial; neoplasm recurrence, local; anemia; blood toxicity; stomatitis; antineoplastic activity; temsirolimus; lymphocytopenia; drug fatality; glioblastoma; recurrent disease; glioblastoma multiforme; hypercholesterolemia; tumor growth; cancer control; drug dose regimen; infusions, intravenous; lymphopenia; rapamycin; hyperlipidemia; sirolimus; treatment withdrawal; drug interactions; hypertriglyceridemia; anticonvulsants; efficacy; recurrent; dose time effect relation; cci-779
Journal Title: Investigational New Drugs
Volume: 23
Issue: 4
ISSN: 0167-6997
Publisher: Springer  
Date Published: 2005-08-01
Start Page: 357
End Page: 361
Language: English
DOI: 10.1007/s10637-005-1444-0
PUBMED: 16012795
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 189" - "Export Date: 24 October 2012" - "CODEN: INNDD" - "Source: Scopus"
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  1. Jeffrey J Raizer
    22 Raizer