title: Temsirolimus for patients with metastatic renal cell carcinoma: outcomes in patients receiving temsirolimus within a compassionate use program in a tertiary referral center.
abstract: OBJECTIVE
  Temsirolimus has shown efficacy as first-line treatment of patients with metastatic renal cell carcinoma and poor prognostic features. The efficacy of temsirolimus in other clinical settings, such as second-line therapy, is unclear. The aim of this study was to investigate the outcomes of an unselected group of patients with renal cancer treated with temsirolimus in a compassionate use program.
  
  
  METHODS
  This retrospective analysis included all patients receiving temsirolimus at a tertiary referral center between November 2007 and October 2008. Information was obtained through review of patient notes, electronic records, and pharmacy records. Baseline characteristics, prognostic features, and previous treatments were recorded for all patients. Outcome measures were response rate, progression-free survival (PFS), overall survival (OS), and toxicities.
  
  
  RESULTS
  Thirty-eight patients were included in the analysis, with median age of 62 years, among whom 37% were untreated and 63% had received one or more previous treatments. Thirty-four percent of the patients had three or more poor prognostic factors. Four patients (11%) achieved a partial response (PR); in all four of these patients, the PR was confirmed by two subsequent computed tomography (CT) scans, and in one patient, the PR lasted for more than 18 months. A total of 34% achieved stable disease, and 50% had disease progression. Median OS was 7.6 months (95% confidence interval [CI] 4.8-10.5), and median PFS was 3.2 months (95% CI 1.0-5.5). Patients with two or fewer poor prognostic factors had a survival of 10.12 months compared with 5.03 months of those with three or more. Median survival was 14.9 months for untreated patients and 6.4 months for previously treated patients.
  
  
  CONCLUSIONS
  Our results indicate some efficacy of temsirolimus in untreated patients with renal tumors and poor-intermediate prognosis, although the limitations of small sample size and retrospective nature must be taken into account. The role of temsirolimus in previously treated patients remains controversial given the recently published results of the INTORSECT trial and the discrepancies between the few published series.
authors.affiliation: Queen Elizabeth Hospital Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK.
authors.forename: Mehran
authors.initials: M
authors.lastname: Afshar
authors.affiliation: Queen Elizabeth Hospital Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK ; Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pascoe
authors.affiliation: Queen Elizabeth Hospital Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK.
authors.forename: Sue
authors.initials: S
authors.lastname: Whitmarsh
authors.affiliation: Queen Elizabeth Hospital Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK ; Cancer Research Unit, Clinical Trials Unit, University of Warwick, Coventry, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: James
authors.affiliation: Queen Elizabeth Hospital Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK ; Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Emilio
authors.initials: E
authors.lastname: Porfiri
mesh_terms: D061605:Administration, Intravenous; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary*; D057176:Compassionate Use Trials; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016019:Survival Analysis; D062606:Tertiary Care Centers; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C401859:temsirolimus; D020123:Sirolimus
keywords: renal cancer; retrospective; survival; toxicity; tumor