Abstract
Background
This study was conducted to assess the efficacy and safety of sorafenib monotherapy in clinical practice settings for Korean patients with hepatocellular carcinoma (HCC) related primarily to HBV infection.
Methods
Medical records of 57 consecutive patients with unresectable or metastatic HCC treated with 400 mg bid sorafenib at the National Cancer Center, Korea between June 2007 and March 2008, were retrospectively reviewed.
Results
The median patient age was 55 years (range, 28–76 years), and all patients had performance status 0–2 and Child–Pugh class A or B disease. HCC was etiologically related to HBV in 79.0% of patients. Eleven patients (19.3%) had modified UICC stage III tumors, 11 (19.3%) had stage IVa, and 35 (61.4%) had stage IVb. Following sorafenib monotherapy, 3 patients (5.3%) achieved a partial response and 18 (35.1%) achieved stable disease, with a disease control rate of 40.4%. The median times to progression (TTP) was 9.1 weeks (95% CI 3.4–14.8 weeks). Multivariate analyses showed that serum alpha-fetoprotein (α-FP) ≥400 ng/mL (HR, 2.810; P = 0.023) and the presence of massive intrahepatic tumors (HR, 7.633; P = 0.033) were independent predictors of shorter TTP. The most common grade 3/4 adverse events were hand-foot syndrome (8.8%), diarrhea (7.0%), and skin rash (7.0%). Exacerbation of underlying chronic hepatitis B was not found.
Conclusion
Sorafenib monotherapy showed better outcomes with tolerable toxicity in Korean advanced HCC patients, who had intrahepatic nodular tumors and/or metastatic tumors, coupled with low levels of serum α-FP.
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References
(1998) A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 28(3):751–755 doi:10.1002/hep.510280322
(2006) Annual Report Cause of Death 2005. National Statistical Office
Abou-Alfa GK, Schwartz L et al (2006) Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24(26):4293–4300
Akaza H, Tsukamoto T et al (2007) Phase II study to investigate the efficacy, safety, and pharmacokinetics of sorafenib in Japanese patients with advanced renal cell carcinoma. Jpn J Clin Oncol 37(10):755–762
Bruix J, Llovet JM (2002) Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 35(3):519–524
Bruix J, Sherman M et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35(3):421–430
Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42(5):1208–1236
Cheng A, Kang Y et al (2008) Randomized phase III trial of sorafenib versus placebo in Asian patients with advanced hepatocellular carcinoma. J Clin Oncol 26:May 20 suppl; abstr 4509
Furuse J, Ishii H et al (2008) Phase I study of sorafenib in Japanese patients with hepatocellular carcinoma. Cancer Sci 99(1):159–165
Giambartolomei S, Covone F et al (2001) Sustained activation of the Raf/MEK/Erk pathway in response to EGF in stable cell lines expressing the Hepatitis C Virus (HCV) core protein. Oncogene 20(20):2606–2610
Llovet JM, Ricci S et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390
Lo CM, Ngan H et al (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35(5):1164–1171
Park JW (2004) Practice guideline for diagnosis and treatment of hepatocellular carcinoma. Korean J Hepatol 10(2):88–98
Park JW, An M et al (2007) Accuracy of clinical criteria for the diagnosis of hepatocellular carcinoma without biopsy in a Hepatitis B virus-endemic area. J Cancer Res Clin Oncol 133(12):937–943
Park KW, Park JW et al (2008) Survival analysis of 904 patients with hepatocellular carcinoma in a hepatitis B virus-endemic area. J Gastroenterol Hepatol 23(3):467–473
Parkin DM (2001) Global cancer statistics in the year 2000. Lancet Oncol 2(9):533–543
Raboisson P, Lenz O et al (2007) Evaluation of the anti-hepatitis C virus effect of novel potent, selective, and orally bioavailable JNK and VEGFR kinase inhibitors. Bioorg Med Chem Lett 17(7):1843–1849
Ratain MJ, Eckhardt SG (2004) Phase II studies of modern drugs directed against new targets: if you are fazed, too, then resist RECIST. J Clin Oncol 22(22):4442–4445
Seong J, Park HC et al (2000) Local radiotherapy for unresectable hepatocellular carcinoma patients who failed with transcatheter arterial chemoembolization. Int J Radiat Oncol Biol Phys 47(5):1331–1335
Shim JH, Park JW et al (2008) Efficacy of combination chemotherapy with capecitabine plus cisplatin in patients with unresectable hepatocellular carcinoma. Cancer Chemother Pharmacol (Epub ahead of print)
Therasse P, Arbuck SG et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216
Ueno S, Tanabe G et al (2002) Prognostic performance of the new classification of primary liver cancer of Japan (4th edition) for patients with hepatocellular carcinoma: a validation analysis. Hepatol Res 24(4):395–403
Wu S, Chen JJ et al (2008) Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncol 9(2):117–123
Zhu AX (2008) Development of sorafenib and other molecularly targeted agents in hepatocellular carcinoma. Cancer 112(2):250–259
Acknowledgments
This work was supported by National Cancer Center, Korea (Grant #0810260-1).
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Shim, J.H., Park, JW., Choi, JI. et al. Practical efficacy of sorafenib monotherapy for advanced hepatocellular carcinoma patients in a Hepatitis B virus-endemic area. J Cancer Res Clin Oncol 135, 617–625 (2009). https://doi.org/10.1007/s00432-008-0496-x
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DOI: https://doi.org/10.1007/s00432-008-0496-x