title: Metronomic capecitabine as second-line treatment in hepatocellular carcinoma after sorafenib failure.
abstract: 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.
authors: Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy. Electronic address: alessandro.granito@unibo.it.
authors: Alessandro
authors: A
authors: Granito
authors: Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: Sara
authors: S
authors: Marinelli
authors: Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: Eleonora
authors: E
authors: Terzi
authors: Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: Fabio
authors: F
authors: Piscaglia
authors: Radiology Unit, Department of Digestive Diseases and Internal Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: Matteo
authors: M
authors: Renzulli
authors: Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: Laura
authors: L
authors: Venerandi
authors: Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: Francesca
authors: F
authors: Benevento
authors: Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors: Luigi
authors: L
authors: Bolondi
mesh_terms: D059250:Administration, Metronomic; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069287:Capecitabine / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077157:Sorafenib; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000069287:Capecitabine; D000077157:Sorafenib
keywords: Hepatocellular carcinoma; Metronomic capecitabine; Second-line treatment