Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation

Franco Trevisani, Giovanni Brandi, Francesca Garuti, Maria Aurelia Barbera, Raffaella Tortora, Andrea Casadei Gardini, Alessandro Granito, Francesco Tovoli, Stefania de Lorenzo, Andrea Lorenzo Inghilesi, Francesco Giuseppe Foschi, Mauro Bernardi, Fabio Marra, Rodolfo Sacco, Giovan Giuseppe Di Costanzo

Research output: Contribution to journalArticlepeer-review


Purpose: Metronomic capecitabine (MC) is a well-tolerated systemic treatment showing promising results in one retrospective study, as second-line therapy after sorafenib failure, in patients with hepatocellular carcinoma (HCC). Methods: 117 patients undergoing MC were compared to 112 patients, eligible for this treatment, but undergoing best supportive care (BSC) after sorafenib discontinuation for toxicity or HCC progression. The two groups were compared for demographic and clinical features. A multivariate regression analysis was conducted to detect independent prognostic factors. To balance confounding factors between the two groups, a propensity score model based on independent prognosticators (performance status, neoplastic thrombosis, causes of sorafenib discontinuation and pre-sorafenib treatment) was performed. Results: Patients undergoing MC showed better performance status, lower tumor burden, lower prevalence of portal vein thrombosis, and better cancer stage. Median (95% CI) post-sorafenib survival (PSS) was longer in MC than in BSC patients [9.5 (7.5–11.6) vs 5.0 (4.2–5.7) months (p < 0.001)]. Neoplastic thrombosis, cause of sorafenib discontinuation, pre-sorafenib treatment and MC were independent prognosticators. The benefit of capecitabine was confirmed in patients after matching with propensity score [PSS: 9.9 (6.8–12.9) vs. 5.8 (4.8–6.8) months, (p = 0.001)]. MC lowered the mortality risk by about 40%. MC achieved better results in patients who stopped sorafenib for adverse events than in those who progressed during it [PSS: 17.3 (10.5–24.1) vs. 7.8 (5.2–10.1) months, (p = 0.035)]. Treatment toxicity was low and easily manageable with dose modulation. Conclusions: MC may be an efficient and safe second-line systemic therapy for HCC patients who discontinued sorafenib for toxicity or tumor progression.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJournal of Cancer Research and Clinical Oncology
Publication statusAccepted/In press - Dec 16 2017


  • Hepatocellular carcinoma
  • Metronomic capecitabine
  • Second-line chemotherapy
  • Survival
  • Toxicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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