Larkin, J. M. G., Clarke, R. E. J., Pickering, L. M. (2009) Everolimus (RAD001) in the treatment of advanced renal cell carcinoma: biology and pathways. MEDICAL ONCOLOGY, 26 (Supple). pp. 40-45. ISSN 1357-0560

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Abstract

Everolimus (RAD001) is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), an intracellular serine/threonine kinase that regulates protein synthesis and cell growth, proliferation and survival. Dysfunction of mTOR has been implicated in a number of human illnesses including cancer and everolimus is used for a variety of therapeutic indications and is under evaluation in clinical trials for the treatment of cancer. Two phase I studies evaluating the dosing, toxicity, pharmacokinetics, pharmacodynamics and potential biomarkers of everolimus in advanced cancer have been reported. Daily doses of 10 mg and weekly doses of 50 mg of everolimus appear to inhibit relevant therapeutic targets in both tumour tissue and in skin but maximum-tolerated doses of everolimus were not determined formally in these studies. A phase III study of everolimus at 10 mg daily in the treatment of patients with advanced renal cell carcinoma who had failed prior treatment with sorafenib or sunitinib has also been reported. In this study everolimus was generally well tolerated, causing rash, stomatitis and fatigue in approximately a third of patients which generally were not severe. Hyperglycaemia, hypertriglyceridaemia and hypercholesterolaemia were reported in approximately two-thirds of patients but again were easy to manage and mainly of mild or moderate severity. Severe infections and non-infectious pneumonitis were reported in less than 5% of study participants but generally responded to standard therapies. Further work is necessary to define mechanisms of activity and toxicity of everolimus in the treatment of advanced renal cell carcinoma.

Item Type:	Article
All Authors:	Larkin, J. M. G., Clarke, R. E. J., Pickering, L. M.
Uncontrolled Keywords:	Mammalian target of rapamycin; mTOR; Everolimus; RAD001; Renal cell carcinoma ENDOTHELIAL GROWTH-FACTOR; CANCER-TREATMENT-GROUP; ADVANCED SOLID TUMORS; MAMMALIAN TARGET; RAPAMYCIN INHIBITOR; PHASE-II; TEMSIROLIMUS CCI-779; DEFOROLIMUS AP23573; INTERFERON-ALPHA; RANDOMIZED-TRIAL
Research teams:	Clinical Units > Medicine
Depositing User:	Users 10 not found.
Date Deposited:	26 Feb 2009 16:13
Last Modified:	07 Sep 2011 15:02
URI:	http://publications.icr.ac.uk/id/eprint/7530

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