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Survival and tolerance to sorafenib in Child-Pugh B patients with hepatocellular carcinoma: a prospective study

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Summary

Sorafenib has been widely used to treat unresectable hepatocellular carcinoma (HCC) but most studies have been done in Child-Pugh A (CP-A) patients with well-preserved liver function. We evaluated the overall survival (OS) and tolerance to sorafenib in a large cohort of Child-Pugh B (CP-B) HCC patients as compared to CP-A HCC patients. We prospectively studied 130 patients with advanced HCC who started sorafenib between January 2011 and December 2015. Patients were classified as CP-A (n = 65) or CP-B (n = 65). The average OS for all 130 patients was 10 months. CP-A patients had a median survival rate significantly longer than CP-B patients: 12 months vs. 6 months. The OS found in our group of CP-B patients was 6.5 months, which is higher than that found in most studies done so far. When stratified, our CP-B patients had better OS than ever reported. The dose of the drug was interrupted due to adverse events (AEs) in 38 (29%) of the patients, of whom 20 (30%) were CP-A patients and 18 (28%) were CP-B patients. This real-life cohort of CP-B HCC patients treated with sorafenib had a higher survival than that described in the literature, with a satisfactory safety profile. Despite the high prevalence of severe AEs in CP-B patients, there were fewer treatment interruptions in this group, indicating that Child-Pugh B patients can tolerate treatment and may benefit from sorafenib.

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References

  1. Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108. https://doi.org/10.3322/caac.21262

    Article  PubMed  Google Scholar 

  2. Llovet JM, Fuster J, Bruix J (2004) The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl 10:S115–S120. https://doi.org/10.1002/lt.20034

    Article  PubMed  Google Scholar 

  3. Reig M, Gazzola A, Di Donato R, Bruix J (2014) Systemic treatment. Best Pract Res Clin Gastroenterol 28(5):921–935 https://www.ncbi.nlm.nih.gov/pubmed/25260318

    Article  PubMed  CAS  Google Scholar 

  4. Llovet JM, Ricci S, Mazzaferro V, Hilgard P et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390. https://doi.org/10.1056/NEJMoa0708857

    Article  PubMed  CAS  Google Scholar 

  5. Cheng AL, Kang YK, Chen Z et al (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomized, double-blind, placebo- controlled trial. Lancet Oncol 10:25–34. https://doi.org/10.1016/S1470-2045(08)70285-7

    Article  PubMed  CAS  Google Scholar 

  6. European Association For The Study Of The Liver; European Organisation ForResearch And Treatment Of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56(4):908–943. https://doi.org/10.1016/j.jhep.2011.12.001

    Article  Google Scholar 

  7. Bruix J, Sherman M (2011) American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084991

    Article  PubMed  Google Scholar 

  8. Oken MM, Creech RH, Tormey DC et al (1982) Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol 5:649–655

    Article  PubMed  CAS  Google Scholar 

  9. Pugh RN, Murray-Lyon IM, Dawson JL et al (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60(8):646–649

    Article  PubMed  CAS  Google Scholar 

  10. Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30(1):052–060

    Article  CAS  Google Scholar 

  11. U.S. Department of health and human services. National Institutes of Health. National Cancer Institute. Common Terminology Criteria for Adverse Events v4.0 (CTCAE). (2009) [cited 2018 Jun 1]; Available from: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/Archive/CTCAE_4.0_2009-05-29_QuickReference_8.5x11.pdf

  12. Wada Y, Takami Y, Tateishi M et al (2016) The efficacy of continued sorafenib treatment after radiologic confirmation of progressive disease in patients with advanced hepatocellular carcinoma. PLoS One 11(1):e0146456. https://doi.org/10.1371/journal.pone.0146456

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Marrero JA, Kudo M, Venook AP et al (2016) Observationl registry of Sorafenib use in clinical practice across child-Pugh subgroups: the GIDEON study. J Hepatol 65:1140–1147. https://doi.org/10.1016/j.jhep.2016.07.020

    Article  PubMed  CAS  Google Scholar 

  14. Abou-Alfa GK, Amadori D, Santoro A et al (2008) Is sorafenib (S) safe and effective in patients (pts) with hepatocellular carcinoma (HCC) and child-Pugh B (CPB) cirrhosis? J Clin Oncol 26(15_suppl):4518. https://doi.org/10.1200/jco.2008.26.15_suppl.4518

    Article  Google Scholar 

  15. Da Fonseca LG, Sousa RB, Bento ASA et al (2015) Safety and efficacy of sorafenib in patients with child-Pugh B advanced hepatocellular carcinoma. Mol Clin Oncol 3:793–796. https://doi.org/10.3892/mco.2015.536

    Article  CAS  Google Scholar 

  16. Chiu J, Tang YF, Yao T et al (2012) The use of single-agent Sorafenib in the treatment of advanced hepatocellular carcinoma patients with underlying child-Pugh B liver cirrhosis. A retrospective analysis of efficacy, safety, and survival benefits. Cancer 118(21):5293–5301. https://doi.org/10.1002/cncr.27543

    Article  PubMed  CAS  Google Scholar 

  17. Ogasawara S, Chiba T, Ooka Y et al (2015) Sorafenib treatment in child-Pugh a and B patients with advanced hepatocellular carcinoma: safety, efficacy and prognostic factors. Investig New Drugs 33:729–739. https://doi.org/10.1007/s10637-015-0237-3

    Article  CAS  Google Scholar 

  18. Abou-Alfa GK, Amadori D, Santoro A et al (2011) Safety and efficacy of Sorafenib in patients with hepatocellular carcinoma (HCC) and child-Pugh a versus B cirrhosis. Gastrointest Cancer Res 4(2):40–44

    PubMed  PubMed Central  Google Scholar 

  19. Federico A, Orditura M, Cotticelli G et al (2015) Safety and efficacy of Sorafenib in patients with advanced hepatocellular carcinoma and child-Pugh a or B cirrhosis. Oncol Lett 9:1628–1632. https://doi.org/10.3892/ol.2015.2960

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Pinter M, Sieghart W, Graziadel I et al (2009) Sorafenib in Unresectable hepatocellular carcinoma from mild to advanced stage liver cirrhosis. Oncologist 14:70–76. https://doi.org/10.1634/theoncologist.2008-0191

    Article  PubMed  Google Scholar 

  21. Hollebecque A, Cattan S, Romano O et al (2011) Safety and efficacy of Sorafenib in hepatocellular carcinoma: the impact of the child-Pugh score. Aliment Pharmacol Ther 34:1193–1201. https://doi.org/10.1111/j.1365-2036.2011.04860.x

    Article  PubMed  CAS  Google Scholar 

  22. Pressiani T, Boni C, Rimassa L et al (2013) Sorafenib in patients with child-Pugh class a and B advanced hepatocellular carcinoma: a prospective feasibility analysis. Ann Oncol 24(2):406–411. https://doi.org/10.1093/annonc/mds343

    Article  PubMed  CAS  Google Scholar 

  23. Pinter M, Sieghart W, Hucke F et al (2011) Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib. Aliment Pharmacol Ther 34:949–959. https://doi.org/10.1111/j.1365-2036.2011.04823.x

    Article  PubMed  CAS  Google Scholar 

  24. Koschny R, Gotthardt D, Koehler C et al (2013) Diarrhea is a positive outcome predictor for Sorafenib treatment of advanced hepatocellular carcinoma. Oncology 84:6–13. https://doi.org/10.1159/000342425

    Article  PubMed  CAS  Google Scholar 

  25. Reig M, Lope CR, Llarch N et al (2013) Dermatologic adverse events within the first 60 days of sorafenib treatment are associated with better overall survival (OS) in patients with hepatocellular carcinoma (HCC). J Hepatol 58(Suppl. 1):S63–S227. https://doi.org/10.1016/S0168-8278(13)60269-X https://www.journal-of-hepatology.eu/article/S0168-8278(13)60269-X/abstract

    Article  Google Scholar 

  26. Raoul J, Adhoute X, Gilabert M, Edeline J (2016) How to assess the efficacy or failure of targeted therapy: deciding when to stop Sorafenib in hepatocellular carcinoma. World J Hepatol 8(35):1541–1546. https://doi.org/10.4254/wjh.v8.i35.1541

    Article  PubMed  PubMed Central  Google Scholar 

  27. Colagrande S, Regini F, Taliani GG et al (2015) Advanced hepatocellular carcinoma and Sorafenib: diagnosis, indications, clinical and radiological Folllow-up. World J Hepatol 7(8):1041–1053. https://doi.org/10.4254/wjh.v7.i8.1041

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Hospital Federal dos Servidores do Estado, Rua Sacadura Cabral, 178, Saúde, Rio de Janeiro, RJ, 20221-903, Brazil

    Cassia Regina Guedes Leal, Daniel Barbosa, Diogo Aquino, Bernardo Carvalho & Paulo de Tarso Pinto

  2. Universidade Federal Fluminense, Niterói, Brazil

    Cassia Regina Guedes Leal & Sérgio Setubal

  3. Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil

    Cristiane Magalhães

  4. Hospital Quinta D’Or, Rio de Janeiro, Brazil

    Elizabeth Balbi & Lucio Pacheco

  5. Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Renata Perez

  6. Instituto D’Or de Pesquisa e Ensino, Rio de Janeiro, Brazil

    Renata Perez

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  1. Cassia Regina Guedes Leal
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  2. Cristiane Magalhães
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  3. Daniel Barbosa
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  4. Diogo Aquino
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Correspondence to Cassia Regina Guedes Leal.

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All authors declare that they have no conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The study protocol was approved by the local Ethics Committee and all patients signed a consent form.

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Leal, C.R.G., Magalhães, C., Barbosa, D. et al. Survival and tolerance to sorafenib in Child-Pugh B patients with hepatocellular carcinoma: a prospective study. Invest New Drugs 36, 911–918 (2018). https://doi.org/10.1007/s10637-018-0621-x

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  • DOI: https://doi.org/10.1007/s10637-018-0621-x

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