title: Randomized phase II trial of sunitinib on an intermittent versus continuous dosing schedule as first-line therapy for advanced renal cell carcinoma.
abstract: OBJECTIVE
  Sunitinib has shown antitumor activity with a manageable safety profile as metastatic renal cell carcinoma (RCC) treatment, when given by the standard intermittent schedule as well as a continuous daily dosing (CDD) schedule. A trial was conducted to compare the schedules.
  
  
  METHODS
  Patients with treatment-naive, clear cell advanced RCC were randomly assigned 1:1 to receive sunitinib 50 mg/d for 4 weeks followed by 2 weeks off treatment (schedule 4/2; n = 146) or 37.5 mg/d on the CDD schedule (n = 146) for up to 2 years. The primary end point was time to tumor progression.
  
  
  RESULTS
  Median time to tumor progression was 9.9 months for schedule 4/2 and 7.1 months for the CDD schedule (hazard ratio, 0.77; 95% CI, 0.57 to 1.04; P = .090). No significant difference was observed in overall survival (23.1 v 23.5 months; P = .615), commonly reported adverse events, or patient-reported kidney cancer symptoms. Schedule 4/2 was statistically superior to CDD in time to deterioration, a composite end point of death, progression, and disease-related symptoms (P = .034). CONCLUSION; There was no benefit in efficacy or safety for continuous dosing of sunitinib compared with the approved 50 mg/d dose on schedule 4/2. Given the numerically longer time to tumor progression with the approved 50 mg/d dose on schedule 4/2, adherence to this dose and schedule remains the treatment goal for patients with advanced RCC.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. motzerr@mskcc.org
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
authors.forename: Mark R
authors.initials: MR
authors.lastname: Olsen
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hudes
authors.forename: John M
authors.initials: JM
authors.lastname: Burke
authors.forename: William J
authors.initials: WJ
authors.lastname: Edenfield
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.forename: John A
authors.initials: JA
authors.lastname: Thompson
authors.forename: David
authors.initials: D
authors.lastname: Cella
authors.forename: Akintunde
authors.initials: A
authors.lastname: Bello
authors.forename: Beata
authors.initials: B
authors.lastname: Korytowsky
authors.forename: Jinyu
authors.initials: J
authors.lastname: Yuan
authors.forename: Olga
authors.initials: O
authors.lastname: Valota
authors.forename: Bridget
authors.initials: B
authors.lastname: Martell
authors.forename: Subramanian
authors.initials: S
authors.lastname: Hariharan
authors.forename: Robert A
authors.initials: RA
authors.lastname: Figlin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D000077210:Sunitinib; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib