PMID- 26250585
OWN - NLM
STAT- MEDLINE
DCOM- 20160719
LR  - 20220311
IS  - 1573-7233 (Electronic)
IS  - 0167-7659 (Linking)
VI  - 34
IP  - 3
DP  - 2015 Sep
TI  - Evaluating the role of treatment-related toxicities in the challenges facing 
      targeted therapies for advanced hepatocellular carcinoma.
PG  - 497-509
LID - 10.1007/s10555-015-9580-2 [doi]
AB  - Advanced hepatocellular carcinoma (aHCC) is a complex disease beset by underlying 
      liver dysfunction and high molecular heterogeneity. Sorafenib, introduced in 
      2007, is considered the standard systemic therapy for aHCC, yet only a minority 
      of patients show objective evidence of a response radiologically, and median 
      overall survival is still under 1 year. Other targeted drugs for the treatment of 
      aHCC have failed to reach their primary endpoints of improved/non-inferior 
      overall survival in comparison with sorafenib in recent phase 3 trials. Toxicity 
      was a significant problem, raising the question as to whether outcomes in aHCC 
      trials are being hindered by high levels of adverse events (AEs), particularly in 
      populations with underlying cirrhosis. This is true of six recently failed phase 
      3 studies involving sunitinib, erlotinib, linifanib, brivanib (two trials), and 
      everolimus, as well as ongoing phase 2 and 3 trials of other drugs that work 
      through similar molecular pathways. This article reviews these drugs' toxicities, 
      with a focus on AEs as a reason for their failure in phase 3 trials of patients 
      with aHCC. We also review completed and ongoing phase 3 studies of combination 
      therapies with sorafenib, as well as toxicities of many of the targeted agents in 
      aHCC, including geographic/ethnic differences, measures of toxicity, and 
      strategies to improve management.
FAU - Palmer, Daniel H
AU  - Palmer DH
AD  - Department of Molecular and Clinical Cancer Medicine, Institute of Translational 
      Medicine, University of Liverpool and Clatterbridge Cancer Centre, The Duncan 
      Building, Daulby Street, Liverpool, L69 3GA, UK. Daniel.Palmer@liverpool.ac.uk.
FAU - Johnson, Phillip J
AU  - Johnson PJ
AD  - Department of Molecular and Clinical Cancer Medicine, Institute of Translational 
      Medicine, University of Liverpool and Clatterbridge Cancer Centre, The Duncan 
      Building, Daulby Street, Liverpool, L69 3GA, UK.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Netherlands
TA  - Cancer Metastasis Rev
JT  - Cancer metastasis reviews
JID - 8605731
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Antineoplastic Agents/*adverse effects
MH  - Carcinoma, Hepatocellular/*drug therapy
MH  - Clinical Trials as Topic
MH  - Humans
MH  - Liver Neoplasms/*drug therapy
MH  - Molecular Targeted Therapy/*adverse effects
OTO - NOTNLM
OT  - Brivanib
OT  - HCC
OT  - Nintedanib
OT  - Sorafenib
OT  - Sunitinib
OT  - Toxicity
EDAT- 2015/08/08 06:00
MHDA- 2016/07/20 06:00
CRDT- 2015/08/08 06:00
PHST- 2015/08/08 06:00 [entrez]
PHST- 2015/08/08 06:00 [pubmed]
PHST- 2016/07/20 06:00 [medline]
AID - 10.1007/s10555-015-9580-2 [pii]
AID - 10.1007/s10555-015-9580-2 [doi]
PST - ppublish
SO  - Cancer Metastasis Rev. 2015 Sep;34(3):497-509. doi: 10.1007/s10555-015-9580-2.