title: Sunitinib in patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  Current treatment options for metastatic renal cell carcinoma (RCC) are limited and there is a need to identify novel and effective therapies. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, which has shown activity in an initial study of cytokine-refractory metastatic RCC patients.
  
  
  OBJECTIVE
  To confirm the antitumor efficacy of sunitinib as second-line treatment in patients with metastatic clear-cell RCC, the predominant cell type of this malignancy.
  
  
  METHODS
  Open-label, single-arm, multicenter clinical trial. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The reported data apply through August 2005. Patients (N = 106) had metastatic clear-cell RCC, which had progressed despite previous cytokine therapy.
  
  
  METHODS
  Repeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle.
  
  
  METHODS
  Assessment of clinical response, degree of tumor regression on imaging studies using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Primary end point was overall objective response rate (complete plus partial). Secondary end points were progression-free survival and safety. Response was evaluated by independent third-party core imaging laboratory and by treating physicians (investigator assessment).
  
  
  RESULTS
  All 106 patients received sunitinib and were included in the intent-to-treat population for safety analyses. Of these, 105 patients were evaluable for efficacy analyses. The objective response rate according to an independent third-party assessment resulted in 36 patients with partial response (34%; 95% confidence interval, 25%-44%), and a median progression-free survival of 8.3 months (95% confidence interval, 7.8-14.5 months). The most common adverse events experienced by patients were fatigue in 30 (28%) and diarrhea 21 (20%). Neutropenia, elevation of lipase, and anemia were the most common laboratory abnormalities observed in 45 (42%), 30 (28%), and 27 (26%) patients, respectively.
  
  
  CONCLUSIONS
  The results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00077974.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. motzerr@mskcc.org
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Bukowski
authors.forename: Brendan D
authors.initials: BD
authors.lastname: Curti
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hudes
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Redman
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
authors.forename: Jaime R
authors.initials: JR
authors.lastname: Merchan
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Ginsberg
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bacik
authors.forename: Sindy T
authors.initials: ST
authors.lastname: Kim
authors.forename: Charles M
authors.initials: CM
authors.lastname: Baum
authors.forename: M Dror
authors.initials: MD
authors.lastname: Michaelson
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000077210:Sunitinib