title: Temsirolimus in VEGF-refractory metastatic renal cell carcinoma.
abstract: BACKGROUND
  Temsirolimus is an i.v. administered inhibitor of mammalian target of rapamycin with activity in the first-line setting in poor-prognosis patients with metastatic renal cell carcinoma (RCC). The efficacy of this agent after failure of prior inhibitors of vascular endothelial growth factor (VEGF) is unknown.
  
  
  METHODS
  a retrospective review of patients with metastatic RCC treated at the Cleveland Clinic Taussig Cancer Institute and three regional cancer centers in Ontario, Canada, through the Torisel (temsirolimus) Compassionate Use Program was conducted. Demographic, toxicity and response data were collected.
  
  
  RESULTS
  a total of 87 patients with metastatic RCC were identified who had previously been treated with inhibitors of VEGF subsequently treated with temsirolimus. The majority of patients had either intermediate or poor-prognosis disease at baseline. Expected toxic effects including hyperglycemia and noninfectious pneumonitis were observed. The RECIST-defined objective response rate was 5% and the stable disease rate was 65%. The median time to progression (TTP) was 3.9 months (95% confidence interval 2.8-4.8 months), and median overall survival was 11.2 months.
  
  
  CONCLUSIONS
  in a cohort of pre-treated intermediate to poor-prognosis patients with metastatic RCC, weekly i.v. temsirolimus is associated with predictable, but manageable toxicity, and a TTP approaching 4 months.
authors.affiliation: Department of Medical Oncology, London Regional Cancer Program, London, Ontario, Canada. Electronic address: Mary.mackenzie@lhsc.on.ca.
authors.forename: M J
authors.initials: MJ
authors.lastname: MacKenzie
authors.affiliation: Department of Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: B I
authors.initials: BI
authors.lastname: Rini
authors.affiliation: Department of Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: P
authors.initials: P
authors.lastname: Elson
authors.affiliation: Department of Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Schwandt
authors.affiliation: Department of Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wood
authors.affiliation: Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre.
authors.forename: M
authors.initials: M
authors.lastname: Trinkhaus
authors.affiliation: Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre.
authors.forename: G
authors.initials: G
authors.lastname: Bjarnason
authors.affiliation: Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Knox
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D057176:Compassionate Use Trials; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012189:Retrospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C401859:temsirolimus; D020123:Sirolimus