PURPOSE: This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib. MATERIALS AND 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.
PURPOSE: This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib. MATERIALS AND 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: Brian I Rini; M Dror Michaelson; Jonathan E Rosenberg; Ronald M Bukowski; Jeffrey A Sosman; Walter M Stadler; Thomas E Hutson; Kim Margolin; Charles S Harmon; Samuel E DePrimo; Sindy T Kim; Isan Chen; Daniel J George Journal: J Clin Oncol Date: 2008-08-01 Impact factor: 44.544
Authors: Brian I Rini; George Wilding; Gary Hudes; Walter M Stadler; Sinil Kim; Jamal Tarazi; Brad Rosbrook; Peter C Trask; Laura Wood; Janice P Dutcher Journal: J Clin Oncol Date: 2009-08-03 Impact factor: 44.544
Authors: Daniel H Albert; Paul Tapang; Terrance J Magoc; Lori J Pease; David R Reuter; Ru-Qi Wei; Junling Li; Jun Guo; Peter F Bousquet; Nayereh S Ghoreishi-Haack; Baole Wang; Gail T Bukofzer; Yi-Chun Wang; Jason A Stavropoulos; Kresna Hartandi; Amanda L Niquette; Nirupama Soni; Eric F Johnson; J Owen McCall; Jennifer J Bouska; Yanping Luo; Cherrie K Donawho; Yujia Dai; Patrick A Marcotte; Keith B Glaser; Michael R Michaelides; Steven K Davidsen Journal: Mol Cancer Ther Date: 2006-04 Impact factor: 6.261
Authors: M R Matrana; C Duran; A Shetty; L Xiao; B J Atkinson; P Corn; L C Pagliaro; R E Millikan; C Charnsangave; E Jonasch; N M Tannir Journal: Eur J Cancer Date: 2013-06-26 Impact factor: 9.162
Authors: Shundong Ji; Yang Zhou; Martin J Voorbach; Guoqiang Shao; Yumin Zhang; Gerard B Fox; Daniel H Albert; Yanping Luo; Shuang Liu; Sarah R Mudd Journal: J Pharmacol Exp Ther Date: 2013-06-07 Impact factor: 4.030