Sorafenib for treatment of hepatocellular carcinoma: A systematic review

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Background Sorafenib, a drug that inhibits Raf serine/threonine kinases mediating cell proliferation and receptor tyrosine kinases involved in angiogenesis, is approved for treatment of advanced hepatocellular carcinoma. Aims To explore the efficacy and safety of sorafenib for treating advanced HCC, and to identify clinical factors that might affect that efficacy and safety. Methods We conducted a systematic review using the PRISMA guidelines to identify prospective studies on sorafenib used alone or in combination with systemic and/or loco regional anti-tumor therapy for treating advanced HCC. Results We identified 21 prospective trials of sorafenib treatment alone (7) or combined with other treatment (14). In randomized, placebo-controlled trials, sorafenib prolonged overall survival by 2.3-2.8 months, extended the time to tumor progression by 1.4-2.7 months, and increased disease control by 11-19 %. OS and DCRs were lowest for studies with the highest percentage of hepatitis B patients. Most studies reported major side effects (diarrhea, fatigue, and hand-foot syndrome) in \15 % of patients, with greater incidence in patients with advanced cirrhosis and those treated with sorafenib in combination with 5-FU drugs. Conclusions Treatment with sorafenib results in statistically significant, but clinically modest, improvements in OS, TTP, and DCR. For patients with hepatitis B, response seems to be poorer than for those with hepatitis C. The frequency of hand-foot syndrome seems to be higher when sorafenib is used in advanced cirrhosis and is combined with 5-FU drugs. It is not clear that sorafenib combined with other treatments is more effective than sorafenib alone.

Original languageEnglish (US)
Pages (from-to)1122-1129
Number of pages8
JournalDigestive Diseases and Sciences
Volume57
Issue number5
DOIs
StatePublished - May 2012

Fingerprint

Hepatocellular Carcinoma
Hand-Foot Syndrome
Therapeutics
Hepatitis B
Fluorouracil
Fibrosis
raf Kinases
sorafenib
Pharmaceutical Preparations
Safety
Protein-Serine-Threonine Kinases
Receptor Protein-Tyrosine Kinases
Hepatitis C
Fatigue
Diarrhea
Neoplasms
Randomized Controlled Trials
Placebos
Cell Proliferation
Prospective Studies

Keywords

  • Cirrhosis
  • Hepatocellular carcinoma
  • Sorafenib
  • Systematic review
  • Transarterial chemoembolization

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Sorafenib for treatment of hepatocellular carcinoma : A systematic review. / Xie, Bingru; Wang, David H.; Spechler, Stuart Jon.

In: Digestive Diseases and Sciences, Vol. 57, No. 5, 05.2012, p. 1122-1129.

Research output: Contribution to journalArticle

@article{9a6179fb281c4519bb0909e01f5ab981,
title = "Sorafenib for treatment of hepatocellular carcinoma: A systematic review",
abstract = "Background Sorafenib, a drug that inhibits Raf serine/threonine kinases mediating cell proliferation and receptor tyrosine kinases involved in angiogenesis, is approved for treatment of advanced hepatocellular carcinoma. Aims To explore the efficacy and safety of sorafenib for treating advanced HCC, and to identify clinical factors that might affect that efficacy and safety. Methods We conducted a systematic review using the PRISMA guidelines to identify prospective studies on sorafenib used alone or in combination with systemic and/or loco regional anti-tumor therapy for treating advanced HCC. Results We identified 21 prospective trials of sorafenib treatment alone (7) or combined with other treatment (14). In randomized, placebo-controlled trials, sorafenib prolonged overall survival by 2.3-2.8 months, extended the time to tumor progression by 1.4-2.7 months, and increased disease control by 11-19 {\%}. OS and DCRs were lowest for studies with the highest percentage of hepatitis B patients. Most studies reported major side effects (diarrhea, fatigue, and hand-foot syndrome) in \15 {\%} of patients, with greater incidence in patients with advanced cirrhosis and those treated with sorafenib in combination with 5-FU drugs. Conclusions Treatment with sorafenib results in statistically significant, but clinically modest, improvements in OS, TTP, and DCR. For patients with hepatitis B, response seems to be poorer than for those with hepatitis C. The frequency of hand-foot syndrome seems to be higher when sorafenib is used in advanced cirrhosis and is combined with 5-FU drugs. It is not clear that sorafenib combined with other treatments is more effective than sorafenib alone.",
keywords = "Cirrhosis, Hepatocellular carcinoma, Sorafenib, Systematic review, Transarterial chemoembolization",
author = "Bingru Xie and Wang, {David H.} and Spechler, {Stuart Jon}",
year = "2012",
month = "5",
doi = "10.1007/s10620-012-2136-1",
language = "English (US)",
volume = "57",
pages = "1122--1129",
journal = "Digestive Diseases and Sciences",
issn = "0163-2116",
publisher = "Springer New York",
number = "5",

}

TY - JOUR

T1 - Sorafenib for treatment of hepatocellular carcinoma

T2 - A systematic review

AU - Xie, Bingru

AU - Wang, David H.

AU - Spechler, Stuart Jon

PY - 2012/5

Y1 - 2012/5

N2 - Background Sorafenib, a drug that inhibits Raf serine/threonine kinases mediating cell proliferation and receptor tyrosine kinases involved in angiogenesis, is approved for treatment of advanced hepatocellular carcinoma. Aims To explore the efficacy and safety of sorafenib for treating advanced HCC, and to identify clinical factors that might affect that efficacy and safety. Methods We conducted a systematic review using the PRISMA guidelines to identify prospective studies on sorafenib used alone or in combination with systemic and/or loco regional anti-tumor therapy for treating advanced HCC. Results We identified 21 prospective trials of sorafenib treatment alone (7) or combined with other treatment (14). In randomized, placebo-controlled trials, sorafenib prolonged overall survival by 2.3-2.8 months, extended the time to tumor progression by 1.4-2.7 months, and increased disease control by 11-19 %. OS and DCRs were lowest for studies with the highest percentage of hepatitis B patients. Most studies reported major side effects (diarrhea, fatigue, and hand-foot syndrome) in \15 % of patients, with greater incidence in patients with advanced cirrhosis and those treated with sorafenib in combination with 5-FU drugs. Conclusions Treatment with sorafenib results in statistically significant, but clinically modest, improvements in OS, TTP, and DCR. For patients with hepatitis B, response seems to be poorer than for those with hepatitis C. The frequency of hand-foot syndrome seems to be higher when sorafenib is used in advanced cirrhosis and is combined with 5-FU drugs. It is not clear that sorafenib combined with other treatments is more effective than sorafenib alone.

AB - Background Sorafenib, a drug that inhibits Raf serine/threonine kinases mediating cell proliferation and receptor tyrosine kinases involved in angiogenesis, is approved for treatment of advanced hepatocellular carcinoma. Aims To explore the efficacy and safety of sorafenib for treating advanced HCC, and to identify clinical factors that might affect that efficacy and safety. Methods We conducted a systematic review using the PRISMA guidelines to identify prospective studies on sorafenib used alone or in combination with systemic and/or loco regional anti-tumor therapy for treating advanced HCC. Results We identified 21 prospective trials of sorafenib treatment alone (7) or combined with other treatment (14). In randomized, placebo-controlled trials, sorafenib prolonged overall survival by 2.3-2.8 months, extended the time to tumor progression by 1.4-2.7 months, and increased disease control by 11-19 %. OS and DCRs were lowest for studies with the highest percentage of hepatitis B patients. Most studies reported major side effects (diarrhea, fatigue, and hand-foot syndrome) in \15 % of patients, with greater incidence in patients with advanced cirrhosis and those treated with sorafenib in combination with 5-FU drugs. Conclusions Treatment with sorafenib results in statistically significant, but clinically modest, improvements in OS, TTP, and DCR. For patients with hepatitis B, response seems to be poorer than for those with hepatitis C. The frequency of hand-foot syndrome seems to be higher when sorafenib is used in advanced cirrhosis and is combined with 5-FU drugs. It is not clear that sorafenib combined with other treatments is more effective than sorafenib alone.

KW - Cirrhosis

KW - Hepatocellular carcinoma

KW - Sorafenib

KW - Systematic review

KW - Transarterial chemoembolization

UR - http://www.scopus.com/inward/record.url?scp=84863606957&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863606957&partnerID=8YFLogxK

U2 - 10.1007/s10620-012-2136-1

DO - 10.1007/s10620-012-2136-1

M3 - Article

C2 - 22451120

AN - SCOPUS:84863606957

VL - 57

SP - 1122

EP - 1129

JO - Digestive Diseases and Sciences

JF - Digestive Diseases and Sciences

SN - 0163-2116

IS - 5

ER -