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. 2018 Feb;144(2):403-414.
doi: 10.1007/s00432-017-2556-6. Epub 2017 Dec 16.

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

Franco Trevisani  1 , Giovanni Brandi  2 , Francesca Garuti  3 , Maria Aurelia Barbera  2 , Raffaella Tortora  4 , Andrea Casadei Gardini  5 , Alessandro Granito  6 , Francesco Tovoli  6 , Stefania De Lorenzo  2 , Andrea Lorenzo Inghilesi  7 , Francesco Giuseppe Foschi  8 , Mauro Bernardi  3 , Fabio Marra  7 , Rodolfo Sacco  9 , Giovan Giuseppe Di Costanzo  4
Affiliations

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

Franco Trevisani et al. J Cancer Res Clin Oncol. 2018 Feb.

Abstract

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.

Keywords: Hepatocellular carcinoma; Metronomic capecitabine; Second-line chemotherapy; Survival; Toxicity.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
CONSORT diagram of the study
Fig. 2
Fig. 2
Overall survival of patients from the date of sorafenib discontinuation to death before (a) and after (c) propensity score matching and survival of patients from the start date of sorafenib therapy to death before (b) and after (d) propensity score matching
Fig. 3
Fig. 3
Overall survival of metronomic capecitabine and best supportive care patients according to causes of sorafenib discontinuation
See this image and copyright information in PMC

References

    1. Abdel-Rahman O, Abdel-Wahab M, Shaker M, Abdel-Wahab S, Elbassiony M, Ellithy M (2013) Sorafenib versus capecitabine in the management of advanced hepatocellular carcinoma. Med Oncol 30:655 - PubMed
    1. Brandi G, de Rosa F, Bolondi L, Agostini V, Di Girolamo S, Nobili E, Biasco G (2010) Durable complete response of hepatocellular carcinoma after metronomic capecitabine. Tumori 96:1028–1030 - PubMed
    1. Brandi G, de Rosa F, Agostini V, di Girolamo S, Andreone P, Bolondi L, Serra C, Sama C, Golfieri R, Gramenzi A, Cucchetti A, Pinna AD, Trevisani F, Biasco G, Italian Liver Cancer (ITA.LI.CA) Group (2013) Metronomic capecitabine in advanced hepatocellular carcinoma patients: a phase II study. Oncologist 18:1256–1257 - PMC - PubMed
    1. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodés J, EASL Panel of Experts on HCC (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35:421–430 - PubMed
    1. Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236 - PubMed

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