title: Everolimus: a new mammalian target of rapamycin inhibitor for the treatment of advanced renal cell carcinoma.
abstract: OBJECTIVE
  To review clinical trials and main characteristics of everolimus, with focus on treatment of advanced renal cell carcinoma.
  
  
  METHODS
  Pertinent data were identified primarily through a search of MEDLINE and PubMed (1966-November 2010) using the primary search terms everolimus, RAD001, renal cell carcinoma, and mTOR inhibitors.
  
  
  METHODS
  Studies evaluating the safety and efficacy of everolimus in patients with cancer were evaluated, including Phase 1, 2, and 3 trials. Preference was given to Phase 2 and 3 studies evaluating use of everolimus in patients with renal cell carcinoma.
  
  
  RESULTS
  Everolimus is an oral mammalian target of rapamycin (mTOR) inhibitor approved for the management of patients with advanced renal cell carcinoma who progressed on tyrosine kinase inhibitor therapy. Actions of everolimus within the mTOR pathway result in decreased protein synthesis and cell cycle arrest, as well as decreased angiogenesis. A usual starting dose for patients with renal cell carcinoma is 10 mg daily. Everolimus undergoes extensive hepatic metabolism, primarily through the CYP3A4 isoenzyme, which predisposes it to drug interactions with inducers and inhibitors of this enzyme. Most commonly reported adverse events associated with everolimus include anemia, hyperglycemia, hypercholesterolemia, mucositis, fatigue, and rash. Approval of everolimus was based on the results of a Phase 3 trial that demonstrated an increase in median progression-free survival by 2.1 months in patients receiving everolimus therapy as compared to placebo. The drug was recently added to the National Comprehensive Cancer Network guidelines as a treatment option for patients with advanced renal cell carcinoma who have progressed on tyrosine kinase therapy.
  
  
  CONCLUSIONS
  Based on a review of the currently available literature, everolimus provides a safe and efficacious treatment option for patients with renal cell carcinoma who have progressed on treatment with sunitinib and/or sorafenib.
authors.affiliation: Department of Pharmacy, Duke University Medical Center, Durham, NC, USA. tatjana.grgic@duke.edu
authors.forename: Tatjana
authors.initials: T
authors.lastname: Grgic
authors.forename: Lydia
authors.initials: L
authors.lastname: Mis
authors.forename: Julia M
authors.initials: JM
authors.lastname: Hammond
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism; D016527:Drug Costs; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus