PMID- 22078932
OWN - NLM
STAT- MEDLINE
DCOM- 20120112
LR  - 20220602
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Print)
IS  - 0959-8049 (Linking)
VI  - 47
IP  - 18
DP  - 2011 Dec
TI  - Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer 
      after sunitinib failure.
PG  - 2706-14
LID - 10.1016/j.ejca.2011.09.002 [doi]
AB  - 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.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Tannir, Nizar M
AU  - Tannir NM
AD  - University of Texas, MD Anderson Cancer Center, Houston, 77030, USA. 
      ntannir@mdanderson.org
FAU - Wong, Yu-Ning
AU  - Wong YN
FAU - Kollmannsberger, Christian K
AU  - Kollmannsberger CK
FAU - Ernstoff, Marc S
AU  - Ernstoff MS
FAU - Perry, David J
AU  - Perry DJ
FAU - Appleman, Leonard J
AU  - Appleman LJ
FAU - Posadas, Edwin M
AU  - Posadas EM
FAU - Cho, Daniel
AU  - Cho D
FAU - Choueiri, Toni K
AU  - Choueiri TK
FAU - Coates, Andrew
AU  - Coates A
FAU - Gupta, Neeraj
AU  - Gupta N
FAU - Pradhan, Rajendra
AU  - Pradhan R
FAU - Qian, Jiang
AU  - Qian J
FAU - Chen, Jihong
AU  - Chen J
FAU - Scappaticci, Frank A
AU  - Scappaticci FA
FAU - Ricker, Justin L
AU  - Ricker JL
FAU - Carlson, Dawn M
AU  - Carlson DM
FAU - Michaelson, M Dror
AU  - Michaelson MD
LA  - eng
SI  - ClinicalTrials.gov/NCT00486538
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20111110
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Indazoles)
RN  - 0 (Indoles)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Pyrroles)
RN  - CO93X137CW (linifanib)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy/mortality
MH  - Female
MH  - Humans
MH  - Indazoles/adverse effects/*therapeutic use
MH  - Indoles/adverse effects/*therapeutic use
MH  - Kidney Neoplasms/*drug therapy/mortality
MH  - Male
MH  - Middle Aged
MH  - Phenylurea Compounds/adverse effects/*therapeutic use
MH  - Pyrroles/adverse effects/*therapeutic use
MH  - Sunitinib
MH  - Treatment Failure
PMC - PMC4167844
MID - NIHMS610239
COIS- Conflict of Interest Statement The other authors have no conflicts of interest.
EDAT- 2011/11/15 06:00
MHDA- 2012/01/13 06:00
PMCR- 2014/09/19
CRDT- 2011/11/15 06:00
PHST- 2011/07/21 00:00 [received]
PHST- 2011/09/08 00:00 [revised]
PHST- 2011/09/12 00:00 [accepted]
PHST- 2011/11/15 06:00 [entrez]
PHST- 2011/11/15 06:00 [pubmed]
PHST- 2012/01/13 06:00 [medline]
PHST- 2014/09/19 00:00 [pmc-release]
AID - S0959-8049(11)00713-1 [pii]
AID - 10.1016/j.ejca.2011.09.002 [doi]
PST - ppublish
SO  - Eur J Cancer. 2011 Dec;47(18):2706-14. doi: 10.1016/j.ejca.2011.09.002. Epub 2011 
      Nov 10.