Asian Pacific Journal of Cancer Prevention

Asian Pacific Organization for Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Sorafenib Continuation after First Disease Progression Could Reduce Disease Flares and Provide Survival Benefits in Patients with Hepatocellular Carcinoma: a Pilot Retrospective Study

  • Fu, Si-Rui (Department of Interventional Oncology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital Guangdong Academy of Medical Sciences) ;
  • Zhang, Ying-Qiang (Department of Interventional Oncology, The First Affiliate Hospital, Sun Yat-Sen University) ;
  • Li, Yong (Department of Interventional Oncology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital Guangdong Academy of Medical Sciences) ;
  • Hu, Bao-Shan (Department of Interventional Oncology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital Guangdong Academy of Medical Sciences) ;
  • He, Xu (Department of Interventional Oncology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital Guangdong Academy of Medical Sciences) ;
  • Huang, Jian-Wen (Department of Interventional Oncology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital Guangdong Academy of Medical Sciences) ;
  • Zhan, Mei-Xiao (Department of Interventional Oncology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital Guangdong Academy of Medical Sciences) ;
  • Lu, Li-Gong (Department of Interventional Oncology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital Guangdong Academy of Medical Sciences) ;
  • Li, Jia-Ping (Department of Interventional Oncology, The First Affiliate Hospital, Sun Yat-Sen University)
  • Published : 2014.04.01

Abstract

Background: Sorafenib is a promising drug for advanced hepatocellular carcinoma (HCC); however, treatment may be discontinued for multiple reasons, such as progressive disease, adverse events, or the cost of treatment. The consequences of sorafenib discontinuation and continuation are uncertain. Materials and Methods: We retrospectively analyzed 88 HCC patients treated with sorafenib from July 2007 to January 2013. Overall survival (OS), post-disease progression overall survival (pOS), and time to disease progression (TTP) were compared for survival analysis. Cox proportional hazard regression was performed to assess the effect of important factors on OS in the overall patient population and on pOS in patients who continued sorafenib treatment. Results: Sorafenib was discontinued and continued in 24 and 64 patients, respectively. The median OS (355 vs 517 days respectively; p=0.015) and median post-PD OS (260 vs 317 days, respectively; p=0.020) were statistically different between the discontinuation and continuation groups. Neither the median time to first PD nor the time to second PD were significantly different between the 2 groups. In the discontinuation group, 3 of the 24 patients (12.5%) suffered disease outbreaks. In Cox proportional hazard regression analysis after correction for confounding factors, BCLC stage (p=0.002) and PD site (p=0.024) were significantly correlated with pOS in patients who continued sorafenib treatment. Conclusions: Sorafenib discontinuation may cause HCC flares or outbreaks. It is advisable to continue sorafenib treatment after first PD, particularly in patients with Barcelona Clinic Liver Cancer stage B disease or only intrahepatic PD.

Keywords

Hepatocellular carcinoma;sorafenib;discontinua tion;continuation;disease progression

File

Download PDF

References

  1. Yang JJ, Chen HJ, Yan HH, et al (2013). Clinical modes of EGFR tyrosine kinase inhibitor failure and subsequent management in advanced non-small cell lung cancer. Lung Cancer, 79, 33-9. https://doi.org/10.1016/j.lungcan.2012.09.016
  2. Yau T, Chan P, NG KK, et al (2009). Phase 2 open-label study of single-agent sorafenib in treating advanced hepatocellular carcinoma in a hepatitis B-endemic Asian population: presence of lung metastasis predicts poor response. Cancer, 115, 428-36. https://doi.org/10.1002/cncr.24029
  3. Pop O, Pirvu A, Toffart AC, Moro-Sibilot D (2012). Disease flare after treatment discontinuation in a patient with EML4-ALK lung cancer and acquired resistance to crizotinib. J Thorac Oncol, 7, 1-2. https://doi.org/10.1097/JTO.0b013e31823d4543
  4. Miyahara K, Nouso K, Morimoto Y, et al (2013). Efficacy of sorafenib beyond first progression in patients with metastatic hepatocellular carcinoma. Hepatol Res, 44, 296-301
  5. Park JW, Koh YH, Kim HB, et al (2012). Phase II study of concurrent transarterial chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma. J Hepatol, 56, 1336-42. https://doi.org/10.1016/j.jhep.2012.01.006
  6. Pinter M, Sieghart W, Graziadei I, et al (2009). Sorafenib in unresectable hepatocellular carcinoma from mild to advanced stage liver cirrhosis. Oncologist, 14, 70-6. https://doi.org/10.1634/theoncologist.2008-0191
  7. Stock P, Monga D, Tan X, et al (2007). Platelet-derived growth factor receptor-alpha: a novel therapeutic target in human hepatocellular cancer. Mol Cancer Ther, 6, 1932-41.
  8. Strumberg D (2005). Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment. Drugs Today, 41, 773-84. https://doi.org/10.1358/dot.2005.41.12.937959
  9. Wang Z, Wu Xl, Zeng WZ, et al (2013). Meta-analysis of the efficacy of sorafenib for hepatocellular carcinoma. Asian Pac J Cancer Prev, 14, 691-4. https://doi.org/10.7314/APJCP.2013.14.2.691
  10. Wilhelm S, Carter C, Lynch M, et al (2006). Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov, 5, 835-44. https://doi.org/10.1038/nrd2130
  11. Worns MA, Weinmann A, Pfingst K, et al (2009). Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma in consideration of concomitant stage of liver cirrhosis. J Clin Gastroenterol, 43, 489-95. https://doi.org/10.1097/MCG.0b013e31818ddfc6
  12. El-Serag HB, Rudolph Kl (2007). Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 132, 2557-76. https://doi.org/10.1053/j.gastro.2007.04.061
  13. Chung YH, Han G, Yoon JH, et al (2013). Interim analysis of START: Study in Asia of the combination of TACE (transcatheter arterial chemoembolization). with sorafenib in patients with hepatocellular carcinoma trial. Int J Cancer, 132, 2448-58. https://doi.org/10.1002/ijc.27925
  14. Dufour JF, Hoppe H, Heim MH, et al (2010). Continuous administration of sorafenib in combination with transarterial chemoembolization in patients with hepatocellular carcinoma: results of a phase I study. Oncologist, 15, 1198-204. https://doi.org/10.1634/theoncologist.2010-0180
  15. Eisenhauer EA, Therasse P, Bogaerts J, et al (2009). New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer, 45, 228-47. https://doi.org/10.1016/j.ejca.2008.10.026
  16. Gedaly R, Angulo P, Hundley J, et al (2010). PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. Anticancer Res, 30, 4951-8.
  17. Huynh H, Ngo VC, Koong HN, et al (2009). Sorafenib and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma. J Cell Mol Med, 13, 2673-83. https://doi.org/10.1111/j.1582-4934.2009.00692.x
  18. Huynh H, Nguyen TT, Chow KH, et al (2003). Over-expression of the mitogen-activated protein kinase (MAPK). kinase (MEK)-MAPK in hepatocellular carcinoma: its role in tumor progression and apoptosis. BMC Gastroenterol, 3, 19. https://doi.org/10.1186/1471-230X-3-19
  19. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  20. Llovet JM, Bru C, Bruix J (1999). Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis, 19, 329-38. https://doi.org/10.1055/s-2007-1007122
  21. Llovet JM, Ricci S, Mazzaferro V, et al (2008). Sorafenib in Advanced Hepatocellular Carcinoma. N Engl J Med, 359, 378-90. https://doi.org/10.1056/NEJMoa0708857
  22. Bruix J, Sherman M (2011b). Management of hepatocellular carcinoma: an update. Hepatology, 53, 1020-2. https://doi.org/10.1002/hep.24199
  23. Avila MA, Berasain C, Sangro B, Prieto J (2006). New therapies for hepatocellular carcinoma. Oncogene, 25, 3866-84. https://doi.org/10.1038/sj.onc.1209550
  24. Berk V, Kaplan MA, Tonyali O, et al (2013). Efficiency and side effects of sorafenib therapy for advanced hepatocellular carcinoma: a retrospective study by the anatolian society of medical oncology. Asian Pac J Cancer Prev, 14, 7367-9. https://doi.org/10.7314/APJCP.2013.14.12.7367
  25. Bruix J, Sherman M (2011a). Management of hepatocellular carcinoma: an update. Hepatology, 53, 1020-2. https://doi.org/10.1002/hep.24199
  26. Carlomagno F, Anaganti S, Guida T, et al (2006). BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst, 98, 326-34. https://doi.org/10.1093/jnci/djj069
  27. Chaft JE, Oxnard GR, Sima CS, et al (2011). Disease flare after tyrosine kinase inhibitor discontinuation in patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib: implications for clinical trial design. Clin Cancer Res, 17, 6298-303. https://doi.org/10.1158/1078-0432.CCR-11-1468
  28. Chen HJ, Yan HH, Yang JJ, et al (2013). Disease flare after egfr tyrosine kinase inhibitor cessation predicts poor survival in patients with non-small cell lung cancer. Pathol Oncol Res, 19, 833-8. https://doi.org/10.1007/s12253-013-9651-z
  29. 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 randomised, double-blind, placebo-controlled trial. Lancet Oncol, 10, 25-34. https://doi.org/10.1016/S1470-2045(08)70285-7

Cited by

  1. Survival of Hepatocellular Carcinoma Patients Treated with Sorafenib beyond Progression vol.5, pp.1-2, 2018, https://doi.org/10.1159/000487635