Sorafenib for treatment of hepatocellular carcinoma: a systematic review - PubMed (original) (raw)

Review

Sorafenib for treatment of hepatocellular carcinoma: a systematic review

Bingru Xie et al. Dig Dis Sci. 2012 May.

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.

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Conflict of interest statement

There is no financial or personal interest to report.

Figures

Figure 1

Figure 1

Sorafenib targets cell proliferation, apoptosis and angiogenesis. Red Xs indicate inhibition by sorafenib. Black arrows/lines indicate established pathways. Pink arrows/lines indicate proposed pathways affected by sorafenib. In tumor cells, sorafenib blocks the Raf/MEK/ERK pathway and induces apoptosis by inhibiting Raf isoforms. Sorafenib also appears to induce apoptosis through mechanisms independent of the Raf/MEK/ERK pathway including inhibition of eIF4E phosphorylation, and downregulation of Mcl-1. In vascular endothelial cells, sorafenib inhibits receptor tyrosine kinases involved in angiogenesis including VEGFR and PDGFR.

Figure 2

Figure 2

Trial selection flow

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