title: Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure.
abstract: OBJECTIVE
  This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib.
  
  
  METHODS
  This open-label, multicentre, phase 2 trial of oral linifanib 0.25 mg/kg/day enrolled patients who had prior nephrectomy and adequate organ function. The primary end-point was objective response rate (ORR) per response evaluation criteria in solid tumors (RECIST) by central imaging. Secondary end-points were progression-free survival (PFS), overall survival (OS) and time to progression (TTP). Safety was also assessed.
  
  
  RESULTS
  Fifty-three patients, median age 61 years (range 40-80) were enrolled (August 2007 to October 2008) across 12 North-American centres. Median number of prior therapies was 2 (range 1-4); 43 patients (81%) had clear-cell histology. ORR was 13.2%, median PFS was 5.4 months (95% Confidence Interval (CI): 3.6, 6.0) and TTP was the same; median OS was 14.5 months (95% CI: 10.8, 24.1). The most common treatment-related adverse events (AEs) were diarrhoea (74%), fatigue (74%) and hypertension (66%), and the most common treatment-related Grade 3/4 AE was hypertension (40%).
  
  
  CONCLUSIONS
  Linifanib demonstrated clinically meaningful activity in patients with advanced RCC after sunitinib failure. At 0.25 mg/kg/day, significant dose modifications were required. An alternative, fixed-dosing strategy is being evaluated in other trials.
authors.affiliation: University of Texas, MD Anderson Cancer Center, Houston, 77030, USA. ntannir@mdanderson.org
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Wong
authors.forename: Christian K
authors.initials: CK
authors.lastname: Kollmannsberger
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
authors.forename: David J
authors.initials: DJ
authors.lastname: Perry
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Appleman
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Posadas
authors.forename: Daniel
authors.initials: D
authors.lastname: Cho
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Andrew
authors.initials: A
authors.lastname: Coates
authors.forename: Neeraj
authors.initials: N
authors.lastname: Gupta
authors.forename: Rajendra
authors.initials: R
authors.lastname: Pradhan
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
authors.forename: Jihong
authors.initials: J
authors.lastname: Chen
authors.forename: Frank A
authors.initials: FA
authors.lastname: Scappaticci
authors.forename: Justin L
authors.initials: JL
authors.lastname: Ricker
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Carlson
authors.forename: M Dror
authors.initials: MD
authors.lastname: Michaelson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007191:Indazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; C513486:linifanib; D000077210:Sunitinib
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