PMID- 25565269
OWN - NLM
STAT- MEDLINE
DCOM- 20150713
LR  - 20181202
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 121
IP  - 10
DP  - 2015 May 15
TI  - A phase II trial of second-line axitinib following prior antiangiogenic therapy 
      in advanced hepatocellular carcinoma.
PG  - 1620-7
LID - 10.1002/cncr.29227 [doi]
AB  - BACKGROUND: Second-line treatment options in advanced hepatocellular carcinoma 
      (HCC) are limited. Axitinib, a selective potent tyrosine kinase inhibitor (TKI) 
      of vascular endothelial growth factor VEGF) receptors 1, 2, and 3, merits 
      exploration in HCC. METHODS: This was a single-arm phase II trial of axitinib in 
      advanced HCC. Eligible patients were Child-Pugh A/B7, with measurable progressive 
      disease after TKIs/antiangiogenic drugs. Axitinib was started at 5 mg twice daily 
      orally, titrated from 2 to 10 mg twice daily as tolerated. The primary end point 
      was tumor control at 16 weeks by RECIST1.1; secondary end points were response 
      rate, comparing response by RECIST1.1 to Choi and modified RECIST, exploring 
      dynamic contrast-enhanced imaging models, safety, progression-free (PFS), and 
      overall survival (OS). RESULTS: Thirty patients were treated. Of 26 patients 
      evaluable for response, there were 3 partial responses (PR) per RECIST1.1; 13 PR 
      by Choi, 6 PR and 1 complete response by modified RECIST. Tumor control rate at 
      16 weeks was 42.3%. Two-week perfusion changes were noted on functional imaging. 
      Of 21 patients with evaluable alpha-fetoprotein response, 43% had >50% decrease from 
      baseline. Most common axitinib-related grade 3/4 adverse events (AEs) were 
      hypertension, thrombocytopenia and diarrhea. Of 11 patients with any grade 
      hypertension, 7 had disease control >36 wks. Four patients discontinued treatment 
      due to AEs. Median PFS was 3.6 months. Median OS was 7.1 months. CONCLUSIONS: 
      With 42.3% tumor control at 16 weeks, primary endpoint was met. Axitinib has 
      shown encouraging tolerable clinical activity in VEGF-pretreated HCC patients but 
      further study should be in a selected population incorporating potential 
      biomarkers of response.
CI  - (c) 2015 American Cancer Society.
FAU - McNamara, Mairead G
AU  - McNamara MG
AD  - Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, 
      Ontario, Canada; The Christie NHS Foundation Trust/University of Manchester, 
      Withington, Manchester, United Kingdom.
FAU - Le, Lisa W
AU  - Le LW
FAU - Horgan, Anne M
AU  - Horgan AM
FAU - Aspinall, Alex
AU  - Aspinall A
FAU - Burak, Kelly W
AU  - Burak KW
FAU - Dhani, Neesha
AU  - Dhani N
FAU - Chen, Eric
AU  - Chen E
FAU - Sinaei, Mehrdad
AU  - Sinaei M
FAU - Lo, Glen
AU  - Lo G
FAU - Kim, Tae Kyoung
AU  - Kim TK
FAU - Rogalla, Patrik
AU  - Rogalla P
FAU - Bathe, Oliver F
AU  - Bathe OF
FAU - Knox, Jennifer J
AU  - Knox JJ
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150106
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Imidazoles)
RN  - 0 (Indazoles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (alpha-Fetoproteins)
RN  - C9LVQ0YUXG (Axitinib)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/*therapeutic use
MH  - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Axitinib
MH  - Biomarkers, Tumor/blood
MH  - Carcinoma, Hepatocellular/blood/blood supply/*drug 
      therapy/metabolism/mortality/pathology
MH  - Disease-Free Survival
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Imidazoles/administration & dosage/adverse effects/*therapeutic use
MH  - Indazoles/administration & dosage/adverse effects/*therapeutic use
MH  - Kaplan-Meier Estimate
MH  - Liver Neoplasms/blood/blood supply/*drug therapy/metabolism/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Patient Selection
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects/*therapeutic 
      use
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism
MH  - Recurrence
MH  - Treatment Outcome
MH  - Vascular Endothelial Growth Factor A/drug effects/metabolism
MH  - alpha-Fetoproteins/metabolism
OTO - NOTNLM
OT  - HCC
OT  - axitinib
OT  - phase II trial
OT  - prior antiangiogenic therapy
OT  - second-line treatment
EDAT- 2015/01/08 06:00
MHDA- 2015/07/15 06:00
CRDT- 2015/01/08 06:00
PHST- 2014/09/06 00:00 [received]
PHST- 2014/11/07 00:00 [revised]
PHST- 2014/11/25 00:00 [accepted]
PHST- 2015/01/08 06:00 [entrez]
PHST- 2015/01/08 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - 10.1002/cncr.29227 [doi]
PST - ppublish
SO  - Cancer. 2015 May 15;121(10):1620-7. doi: 10.1002/cncr.29227. Epub 2015 Jan 6.