Practical Effect of Sorafenib Monotherapy on Advanced Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis
2
조회
0
다운로드
5
인용
0
참고문헌
키워드
초록
Background/Aims: We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC)and portal vein tumor thrombosis (PVTT) in a clinical setting. Methods: In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients,30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. Results: All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B,17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. Conclusions: A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.
Abstract
Background/Aims: We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC)and portal vein tumor thrombosis (PVTT) in a clinical setting. Methods: In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients,30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. Results: All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B,17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. Conclusions: A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.
참고문헌 (29)
- Parkin DM, "Global cancer statistics, 2002", CA Cancer J Clin, 55, pp.74~108 (2005)
- Bruix J, "Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma", Hepatology, 42, pp.1208~1236 (2005)
- Llovet JM, "Hepatocellular carcinoma", Lancet, 362, pp.1907~1917 (2003)
- Wilhelm SM, "BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF", MEK, Cancer Res, pp.2004, 64[DOI]
- Villanueva A, "Genomics and signaling pathways in hepatocellular carcinoma", Semin Liver Dis, 27, pp.55~76 (2007)
- Chang YS, "Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models", Cancer Chemother Pharmacol, 59, pp.561~574 (2007)
- Llovet JM, "Sorafenib in advanced hepatocellular carcinoma", N Engl J Med, 359, pp.378~390 (2008)
- Yamakado K, "Clinical efficacy of portal vein stent placement in patients with hepatocellular carcinoma invading the main portal vein", J Hepatol, 30, pp.660~668 (1999)
- The Cancer of the Liver Italian Program (CLIP) investigators, "A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients", Hepatology, 28, pp.751~755 (1998)
- Nihon Kangan Kenkyukai, "The general rules for the clinical and pathological study of primary liver cancer. 5th ed" (2008), Kanehara Shuppan
- Ando E, "A novel chemotherapy for advanced hepatocellular carcinoma with tumor thrombosis of the main trunk of the portal vein", Cancer, 79, pp.1890~1896 (1997)
- Iwamiya T, "Repeated arterial infusion chemotherapy for inoperable hepatocellular carcinoma using an implantable drug delivery system", Cancer Chemother Pharmacol, (33 Suppl), pp.S134~S138 (1994)
- Chen SC, "The effect of external radiotherapy in treatment of portal vein invasion in hepatocellular carcinoma", Cancer Chemother Pharmacol, (33 Suppl), pp.S124~S127 (1994)
- Cheng AL, "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 ONCOLOGY, 10(0), pp.25~34 (2009), LANCET LTD, 84 THEOBALDS RD, LONDON, ENGLAND, WC1X 8RR
- Park JW, "Korean Liver Cancer Study Group and National Cancer Center. Practice guideline for diagnosis and treatment of hepatocellular carcinoma", Korean J Hepatol, 10, pp.88~98 (2004)
- Lacouture ME, "Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib", Oncologist, 13, pp.1001~1011 (2008)
- Lencioni R, "Modified RECIST (mRECIST) assessment for hepatocellular carcinoma", Semin Liver Dis, 30, pp.52~60 (2010)
- Shah ZK, "Enhancing and expansile portal vein thrombosis: value in the diagnosis of hepatocellular carcinoma in patients with multiple hepatic lesions", AJR Am J Roentgenol, 188, pp.1320~1323 (2007)
- Rossi S, "Contrast-enhanced ultrasonography and spiral computed tomography in the detection and characterization of portal vein thrombosis complicating hepatocellular carcinoma", Eur Radiol, 18, pp.1749~1756 (2008)
- Ueno S, "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, pp.395~403 (2002)
- Li Q, "Correlation of four vascular specific growth factors with carcinogenesis and portal vein tumor thrombus formation in human hepatocellular carcinoma", J Exp Clin Cancer Res, 25, pp.403~409 (2006)
- Leung TW, "Factors predicting response and survival in 149 patients with unresectable hepatocellular carcinoma treated by combination cisplatin, interferon-alpha, doxoruTable bicin and 5-fluorouracil chemotherapy", Cancer, 94, pp.421~427 (2002)
- Stuart KE, "Hepatocellular carcinoma in the United States. Prognostic features, treatment outcome, and survival", Cancer, 77, pp.2217~2222 (1996)
- Vora SR, "Serum alpha-fetoprotein response as a surrogate for clinical outcome in patients receiving systemic therapy for advanced hepatocellular carcinoma", Oncologist, 14, pp.717~725 (2009)
- Zhang Z, "Phosphorylated ERK is a potential predictor of sensitivity to sorafenib when treating hepatocellular carcinoma: evidence from an in vitro study", BMC Med, 7, pp.41~ (2009)
- Yu W, "Sorafenib potentiates irradiation effect in hepatocellular carcinoma in vitro and in vivo", Cancer Lett, 329, pp.109~117 (2013)
- Plastaras JP, "Cell cycle dependent and schedule-dependent antitumor effects of sorafenib combined with radiation", Cancer Res, 67, pp.9443~9454 (2007)
- Bhoori S, "Personalized molecular targeted therapy in advanced, recurrent hepatocellular carcinoma after liver transplantation: a proof of principle", J Hepatol, 52, pp.771~775 (2010)
- Hoshida Y, "Molecular classification and novel targets in hepatocellular carcinoma: recent advancements", Semin Liver Dis, 30, pp.35~51 (2010)