title: Temsirolimus: a safety and efficacy review.
abstract: BACKGROUND
  The vascular endothelial growth factor (VEGF) pathway and the mammalian Target of Rapamycin (mTOR) represent the most frequently exploited targets in renal cell carcinoma (RCC). Temsirolimus is an inhibitor of mTOR, and is a unique ester derivative of sirolimus, a macrocyclic lactone, with improved pharmaceutical properties, including stability and solubility. Temsirolimus binds to the cytoplasmic protein FKBP-12, and the complex binds and inhibits mTOR.
  
  
  METHODS
  This review summarizes the clinical findings and safety of temsirolimus in RCC patients.
  
  
  CONCLUSIONS
  A Phase III clinical trial has demonstrated that temsirolimus has statistically significant advantages over treatment with IFN-α in RCC patients with poor prognosis, in terms of OS (overall survival), PFS (progression-free survival), and tumor response. Median OS was improved 49% compared to IFN-α, and median PFS was approximately doubled. It is now considered the standard for RCC patients with poor prognostic features. The possibility that this agent is useful in metastatic non-clear cell carcinoma patients has also been suggested by a subset analysis of the pivotal Phase III trial. Studies in untreated favorable and intermediate risk clear cell and refractory mRCC patients are required.
authors.affiliation: Cleveland Clinic Taussig Cancer Center, Cleveland, OH 44195, USA. bukow464@sbcglobal.net
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Bukowski
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary; D004341:Drug Evaluation; D016903:Drug Monitoring; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D011358:Product Surveillance, Postmarketing; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus