Metronomic capecitabine as second-line treatment in hepatocellular carcinoma after sorafenib failure

Dig Liver Dis. 2015 Jun;47(6):518-22. doi: 10.1016/j.dld.2015.03.010. Epub 2015 Mar 18.


Background: No standard second-line treatments are available for hepatocellular carcinoma patients who fail sorafenib therapy. We assessed the safety and efficacy of metronomic capecitabine after first-line sorafenib failure.

Methods: Retrospective analysis of consecutive hepatocellular carcinoma patients receiving metronomic capecitabine between January 2012 and November 2014. The primary end-point was safety, secondary end-point was efficacy, including time-to-progression and overall survival.

Results: Twenty-six patients (80% Child-Pugh A, 80% Barcelona Clinic Liver Cancer stage C) received metronomic capecitabine (500 mg/bid). Median treatment duration was 3.2 months (range 0.6-31). Fourteen (53%) patients experienced at least one adverse event. The most frequent drug-related adverse events were bilirubin elevation (23%), fatigue (15%), anaemia (11%), lymphoedema (11%), and hand-foot syndrome (7.6%). Treatment was interrupted in 19 (73%) for disease progression, in 4 (15%) for liver deterioration, and in 1 (3.8%) for adverse event. Disease control was achieved in 6 (23%) patients. Median time-to-progression was 4 months (95% confidence interval 3.2-4.7). Median overall survival was 8 months (95% confidence interval 3.7-12.3).

Conclusions: Metronomic capecitabine was well tolerated in hepatocellular carcinoma patients who had been treated with sorafenib. Preliminary data show potential anti-tumour activity with long-lasting disease control in a subgroup of patients that warrants further evaluation in a phase III study.

Keywords: Hepatocellular carcinoma; Metronomic capecitabine; Second-line treatment.

Publication types

  • Evaluation Study

MeSH terms

  • Administration, Metronomic
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Capecitabine / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Female
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use*
  • Retrospective Studies
  • Sorafenib
  • Survival Analysis
  • Treatment Failure


  • Antineoplastic Agents
  • Phenylurea Compounds
  • Niacinamide
  • Capecitabine
  • Sorafenib