Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastatic renal cell carcinoma has harboured a poor prognosis for decades with immunotherapy being the only available therapy with high toxicity and modest effect. Dependance of renal cell carcinoma oncogenesis on the mTOR pathway has led to clinical development of temsirolimus in this setting. This sirolimus derivative has shown clinical efficacy in monotherapy for poor-risk renal cell carcinoma leading to an overall survival of 10.8 months in the pivotal phase III trial of this agent. Its specific adverse events consist of metabolic dysregulation (hyperlipemia, hyperglycemia), mucositis, rash and pneumonitis which can be severe and need careful monitoring and management. In this review, we will discuss of the clinical development of this molecule, its efficacy, its safety profile and future perspectives.
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PMID:Renal cell carcinoma: focus on safety and efficacy of temsirolimus. 2123 95

mTOR-inhibitors are part of targeted agents and are already in use in the clinic, especially for treatment of metastatic renal cell carcinoma. Distinct from conventional chemotherapeutics, targeted agents imply chronic treatment, which has changed our perspective on the commerce of adverse events (AE). In principle, mTOR-inhibitors are associated with a broad number of AEs. The occurrence of stomatitis, infection, pneumonitis, hyperlipidemia and hyperglycemia are considered major class effects of mTOR-inhibitors. However, severe adverse events remain scarce among mTOR-inhibitors and support chronic use of these agents. Based on their good clinical tolerability mTOR-inhibitors are prone to be developed in combinational therapies. However, the hepatic metabolism of these agents may limit their use to partners with a distinct metabolism in order to avoid drug interaction. Meanwhile about 40 different trials use mTOR-inhibitors in different tumor entities. The use of mTOR-inhibitors in neuroendocine tumors of the intestine, mantle cell lymphoma and sarcomas has hereby shown to be very promising. The mainstay of therapy already incorporates the use of everolimus in second line and temsirolimus in first line treatment in patients with metastatic renal cell carcinoma.
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PMID:[Use of mTOR-inhibitors in solid tumors]. 2152 29

CASE STUDY Tom, a 75-year-old white male, was recently diagnosed with metastatic renal cell carcinoma (RCC; Tom's case is not an actual clinical case but has been developed by the authors as an exemplar). Two years prior, he had undergone a left partial (laparoscopic) nephrectomy for clear cell RCC. At that time, he had a stage 3 disease (the tumor extended into perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota's fascia [Cancer.net, 2016]), and regularly (every 3-6 months) scheduled surveillance imaging did not show metastatic disease. Recent imaging with a computed tomography (CT) of the chest/abdomen/pelvis revealed small bilateral pulmonary nodules that did not have the radiographic appearance of a primary lung tumor, but rather that of metastatic disease. Therefore, a decision was made to repeat CT scans in a shorter interval (in 6 weeks) to assess growth kinetics. Subsequent CT scan showed an increase in size and number of pulmonary nodules, so the decision was made to begin systemic treatment. At the time of Tom's metastatic evaluation, his Eastern Cooperative Oncology Group performance status was 0 as he was asymptomatic and fully active (Table 1). He was classified as favorable risk according to Heng criteria (Table 2). Tom is married and lives with his wife. He is independent in his self-care but also relies on his wife for health-care decision-making. He does not drink alcohol and is a former smoker with a history of 30 pack-years. Tom's medical history includes hypertension that is adequately controlled with lisinopril (20 mg/day), coronary artery disease (on daily aspirin 81 mg) with left ventricular ejection fraction (LVEF) of > 50%, which is within the normal range (50%-75%), benign prostatic hyperplasia for which he is treated with finasteride, and hyperlipidemia that is treated with atorvastatin.
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PMID:Management of Older Patients With Metastatic Renal Cell Carcinoma Receiving Sunitinib: A Hypothetical, Illustrative Case Scenario. 3056 69