Chemotherapy for Advanced Hepatocellular Cancer

Summary and Comment |
November 7, 2013

Chemotherapy for Advanced Hepatocellular Cancer

  1. David H. Ilson, MD, PhD

A trend toward superior overall survival was observed with FOLFOX4 versus doxorubicin.

  1. David H. Ilson, MD, PhD

Advanced Hepatocellular cancer (HCC) is common globally and is becoming more common in the U.S. due to the increasing prevalence of hepatitis C virus infection. The standard of care for advanced HCC is sorafenib, a tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor, RAF, and other tyrosine kinases. To determine the potential benefit of chemotherapy in this setting, international investigators conducted a phase III, multicenter, randomized, open-label trial (EACH), comparing doxorubicin with FOLFOX4 (infusional fluorouracil, leucovorin, and oxaliplatin) in 371 Asian patients with advanced HCC.

Patients received either doxorubicin (50 mg/m2) once every 3 weeks or oxaliplatin (85 mg/m2 on day 1), leucovorin (200 mg/m2 on days 1 and 2) plus fluorouracil (400 mg/m2 on days 1 and 2) and continuous infusion fluorouracil (600 mg/m2 per day for 2 days) once every 2 weeks. Most patients were male (87%–90%) with hepatitis B infection (90%–92%), concurrent cirrhosis (54%–56%), Child-Pugh A liver disease (87%–89%), and distant metastatic disease (57%–60%).

The first two interim analyses indicated that median overall survival (OS) was superior with FOLFOX4 versus doxorubicin (hazard ratio, 0.56, then HR, 0.69). However, at final analysis, a trend toward superior median OS was seen with FOLFOX4 (6.4 vs. 5.0 months; HR, 0.80; P=0.07). Progression-free survival was superior with FOLFOX4 (2.9 vs. 1.8 months; HR, 0.62; P<0.001), as was antitumor response (8.7% vs. 2.7%; P=0.01). Rates of serious adverse events were similar in the two treatment arms.


The EACH trial is the first international randomized study to compare chemotherapy treatments in hepatocellular cancer. Neither treatment demonstrated any significant degree of efficacy. However, the slightly greater response, the longer progression-free survival, and the trend toward superior survival with FOLFOX4 argue that it can be considered a chemotherapy alternative to doxorubicin. Initial therapy with sorafenib, which improves survival, albeit with limited antitumor response, remains the care standard.

  • Disclosures for David H. Ilson, MD, PhD at time of publication Consultant / Advisory board Clovis; Eli-Lilly; ImClone Speaker's bureau Genentech Grant / research support Bayer Editorial boards HemOnc Today; Journal of Clinical Oncology


Reader Comments (1)

singh navdeep Physician, Oncology, ludhiana

Good to see another option for HCC patients.
But , where to place sorafenib ? Before FOLFOX4 or after it .
Dr Navdeep S

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