PMID- 25618828
OWN - NLM
STAT- MEDLINE
DCOM- 20150512
LR  - 20211203
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 51
IP  - 5
DP  - 2015 Mar
TI  - Phase II study of pazopanib as second-line treatment after sunitinib in patients 
      with metastatic renal cell carcinoma: a Southern China Urology Cancer Consortium 
      Trial.
PG  - 595-603
LID - S0959-8049(15)00013-1 [pii]
LID - 10.1016/j.ejca.2015.01.005 [doi]
AB  - This multicentre, single arm, phase II study was aimed to assess the efficacy and 
      safety of pazopanib as second-line treatment after failure of sunitinib in 
      patients with metastatic renal cell carcinoma (mRCC) and explore biomarkers for 
      pazopanib response. Patients received pazopanib 800mgperday. The primary 
      end-point was progression-free survival (PFS). Secondary end-points included 
      objective response rate (ORR), overall survival (OS) and safety. Serum proteins 
      (Delta-like ligand (DLL4), Notch1, hypoxia inducible factor-1alpha (HIF-1alpha), HIF-2alpha, 
      vascular endothelial growth factor A (VEGFA) and platelet-derived growth factor 
      receptor beta (PDGFRB)) levels were measured using enzyme-linked immunosorbent assay 
      (ELISA). 86 patients with clear cell mRCC were enrolled from December 2009 to 
      March 2012 from three centres in Southern China. Of 85 evaluable patients, the 
      median PFS was 5.6months (95% confidence interval (CI), 4.1-6.7months) by 
      independent review. No complete response (CR) was observed in all patients. 13 
      (15.3%; 95% confidence interval [CI], 11.2-23.9%) patients achieved partial 
      responses (PR) (ORR 15.3%). Median OS was 18.1months (95% CI, 13.2-19.8months). 
      The most common adverse events (AEs) were mild to moderate and clinically 
      manageable, including hypertension (37.6%), diarrhoea (36.5%), increased AST 
      (51.8%), and anaemia (60%). AEs resulted in dose reduction in 24.7% of patients. 
      Multivariable analysis showed that higher baseline levels of DLL4 and VEGFA and 
      lower baseline level of HIF-2alpha were associated with shorter PFS; only lower 
      baseline level of HIF-2alpha was correlated with shorter OS. The lower expression 
      level of DLL4 after pazopanib treatment was associated with higher response rate 
      probability. In conclusion, pazopanib was clinically active and well tolerated as 
      second-line treatment after sunitinib in mRCC patients. Baseline levels of serum 
      DLL4, VEGFA and HIF-2alpha may have potential utility as biomarkers of clinical 
      efficacy in this setting (chiCTR-TRC-13004016).
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Xie, Mian
AU  - Xie M
AD  - Laboratory of translational research, The First Affiliated Hospital of Guangzhou 
      Medical University, Guangzhou, China. Electronic address: mianxie@gird.cn.
FAU - He, Chao Sheng
AU  - He CS
AD  - Department of Urology, Guangdong General Hospital, Guangzhou, China.
FAU - Huang, Jin Kun
AU  - Huang JK
AD  - Department of Urology, The First Affiliated Hospital of Guangzhou Medical 
      University, Guangzhou, China.
FAU - Lin, Qi Zhan
AU  - Lin QZ
AD  - Department of Urology, Traditional Chinese Medical Hospital of Guangdong 
      Province, Guangzhou, China.
LA  - eng
SI  - ChiCTR/TRC13004016
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150121
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (DLL4 protein, human)
RN  - 0 (Indazoles)
RN  - 0 (Indoles)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 0 (Sulfonamides)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
RN  - 7RN5DR86CK (pazopanib)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angiogenesis Inhibitors/adverse effects/*therapeutic use
MH  - Basic Helix-Loop-Helix Transcription Factors/blood
MH  - Biomarkers, Tumor/blood
MH  - Calcium-Binding Proteins
MH  - Carcinoma, Renal Cell/blood/*drug therapy/mortality/secondary
MH  - China
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Indazoles
MH  - Indoles/adverse effects/*therapeutic use
MH  - Intercellular Signaling Peptides and Proteins/blood
MH  - Kaplan-Meier Estimate
MH  - Kidney Neoplasms/blood/*drug therapy/mortality/pathology
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Proportional Hazards Models
MH  - Prospective Studies
MH  - Pyrimidines/adverse effects/*therapeutic use
MH  - Pyrroles/adverse effects/*therapeutic use
MH  - Risk Factors
MH  - Sulfonamides/adverse effects/*therapeutic use
MH  - Sunitinib
MH  - Time Factors
MH  - Treatment Failure
MH  - Vascular Endothelial Growth Factor A/blood
OTO - NOTNLM
OT  - Delta-like ligand 4
OT  - Hypoxia-inducible factor
OT  - Metastatic renal cell carcinoma
OT  - Pazopanib
OT  - Phase II
EDAT- 2015/01/27 06:00
MHDA- 2015/05/13 06:00
CRDT- 2015/01/26 06:00
PHST- 2014/08/24 00:00 [received]
PHST- 2014/12/16 00:00 [revised]
PHST- 2015/01/05 00:00 [accepted]
PHST- 2015/01/26 06:00 [entrez]
PHST- 2015/01/27 06:00 [pubmed]
PHST- 2015/05/13 06:00 [medline]
AID - S0959-8049(15)00013-1 [pii]
AID - 10.1016/j.ejca.2015.01.005 [doi]
PST - ppublish
SO  - Eur J Cancer. 2015 Mar;51(5):595-603. doi: 10.1016/j.ejca.2015.01.005. Epub 2015 
      Jan 21.