Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Everolimus (RAD001, Afinitor((R)) Novartis) is the first oral inhibitor of mTOR (mammalian target of rapamycin) to reach the oncology clinic. Everolimus 10 mg daily achieves complete inhibition of its target at below the maximum tolerable dose for most patients. A phase III randomized placebo-controlled trial has examined the impact of everolimus in patients with clear cell renal cancers and progressive disease on or within 6 months of the VEGFR tyrosine kinase inhibitors sunitinib and/or sorafenib. The primary endpoint of progression-free survival was increased from median 1.9 to 4.9 months (hazard ratio 0.33, P < 0.001) and 25% were still progression-free after 10 months of everolimus therapy. There was a delay in time to decline of performance status and trends to improvement in quality of life, disease-related symptoms, and overall survival despite crossover of the majority of patients assigned to placebo. In 2009, everolimus was approved in the US and Europe as the only validated option for this indication. Toxicities are usually mild to moderate and can be managed with dose reduction or interruption if necessary. Opportunistic infections and non-infectious pneumonitis are seen as a class effect. Management of common practical management issues are discussed. Clinical trials are in progress to examine additional roles for everolimus in renal cancer, alone and in combination with other agents.
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PMID:Everolimus: the first approved product for patients with advanced renal cell cancer after sunitinib and/or sorafenib. 2053 64

Several types of pulmonary complications can occur during treatment with targeted therapies: haemoptysis; cough; dyspnoea; pleural effusions, etc. Only bevacizumab seems to be associated with an increased risk of haemoptysis, but this risk is low (less than 2% for haemoptysis greater or equal to grade 3). There are no validated predictive criteria for haemoptysis with bevacizumab in pulmonary metastases of renal cancer. In cases of haemoptysis, its severity must be evaluated and appropriate examinations used to determine its cause. Administration of an mTOR inhibitor, in particular everolimus, is associated with the occurrence of both asymptomatic and potentially life-threatening pneumopathies. In cases of respiratory symptoms with normal chest radiography, a chest CT scan must be carried out, due to its superior sensitivity and specificity in the diagnosis of pneumopathies with everolimus. In cases of pneumopathies with mTOR inhibitors, specialist advice (pulmonologist) is recommended. A bronchoscopy with lavage must be discussed if an opportunistic infection is suspected. A temporary stop to mTOR inhibitor, dose reduction and treatment with corticosteroids are discussed depending on the symptoms.
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PMID:[Management of side effects of targeted therapies in renal cancer: pulmonary side effects]. 2581 31