2011, Number 1
<< Back Next >>
Ann Hepatol 2011; 10 (1)
Advanced hepatocellular carcinoma. Review of targeted molecular drugs
Camargo PAR, Alves D, Guz B, Matos C, Viana M, Harriz M, Terrabuio D, Kondo M, Gampel O, Polletti P
Language: English
References: 40
Page: 21-27
PDF size: 85.09 Kb.
ABSTRACT
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world in terms of incidence, accounting
for approximately 630 thousand new cases per year; in addition, HCC is the third most common
cause of cancer death. Worldwide, the greatest risk factors for HCC are the infections caused by hepatitis
B and C viruses, which increase the risk of developing the disease by about 20 times. The standard treatment
in the early stages of the disease, such as surgical resection, local ablation and liver transplantation,
are able to cure a proportion of patients, but most cases of HCC present in advanced stages, precluding
the use of such treatments with curative intent. In these advanced stages, systemic treatments are commonly
used. Unfortunately, chemotherapy with conventional cytotoxic agents is ineffective and does not
seem to modify the natural history of disease. Treatment options for patients with advanced HCC are extremely
limited, but the identification of signaling pathways, and the recognition of the role of these pathways
in the pathogenesis of the disease resulted in the development of drugs directed at specific
therapeutic targets. One such drug is Sorafenib, a kinase inhibitor with antiangiogenic and antiproliferative
properties. In conclusion, Sorafenib has demonstrated survival benefits in patients with advanced HCC,
thus representing a new standard reference for systemic treatment in these cases.
REFERENCES
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: 74-108.
Donato F, Boffetta P, Puoti M. A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. Int J Cancer 1998; 75: 347-54.
Fassio E, Díaz S, Santa C, Reig ME, Artola YM, Mattos AA, Míguez C, et al. Etiology of hepatocellular carcinoma in Latin America: a prospective, multicenter, international study. Ann Hepatol 2010; 9: 63-9.
Méndez-Sánchez N, Villa AR, Vázquez-Elizondo G, Ponciano- Rodríguez G, Uribe M. Mortality trends for liver cancer in Mexico from 2000 to 2006. Ann Hepatol 2008; 7: 226-9.
Brasil. Ministério da Saúde. Programa Nacional de Hepatites Virais. Avaliação da Assistência às Hepatites Virais no Brasil. Brasília: 2002.
Brasil. Ministério da Saúde. Instituto Nacional de Câncer. Estimativa 2010: incidência de câncer no Brasil. Rio de Janeiro, 2009.
Goncalves CS, Pereira FE, Gayotto LC. Hepatocellular carcinoma in Brazil: report of a national survey (Florianopolis, SC, 1995). Rev Inst Med Trop Sao Paulo 1997; 39: 165-70.
Minguez B, Tovar V, Chiang D, Villanueva A, Llovet JM. Pathogenesis of hepatocellular carcinoma and molecular therapies. Curr Opin Gastroenterol 2009; 25: 186-94.
Conte VP. Carcinoma Hepatocelular. Parte 1. Considerações gerais e diagnóstico. Arq Gastroenterol 2000; 37: 56-68.
Umeda T, Hino O. Molecular aspects of human hepatocarcinogenesis mediated by inflammation: from hypercarcinogenic state to normo- or hypocarcinogenic state. Oncology 2002; 62(Suppl. 1): 38-42.
Mantovani A. Cancer: inflammation by remote control. Nature 2005; 435: 752-3.
Thomas MB, Abbruzzese JL. Opportunities for targeted therapies in hepatocellular carcinoma. J Clin Oncol 2005; 23: 8093-108.
Fujimori M, Tokino T, Hino O, Kitagawa T, Imamura T, Okamoto E, Mitsunobu M, et al. Allelotype study of primary hepatocellular carcinoma. Cancer Res 1991; 51: 89-93.
Tsuda H, Oda T, Sakamoto M, Hirohashi S. Different pattern of chromosomal allele loss in multiple hepatocellular carcinomas as evidence of their multifocal origin. Cancer Res 1992; 52: 1504-9.
Poon RT, Ng IO, Lau C, Yu WC, Fan ST, Wong J. Correlation of serum basic fibroblast growth factor levels with clinicopathologic features and postoperative recurrence in hepatocellular carcinoma. Am J Surg 2001; 182: 298-304.
Méndez-Sánchez N, Vásquez-Fernández F, Zamora-Valdés D, Uribe M. Sorafenib, a systemic therapy for hepatocellular carcinoma. Ann Hepatol 2008; 7: 46-51.
Chaparro M, Gonzalez Moreno L, Trapero-Marugan M, Medina J, Moreno-Otero R. Review article: pharmacological therapy for hepatocellular carcinoma with sorafenib and other oral agents. Aliment Pharmacol Ther 2008; 28: 1269-77.
Llovet JM, Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology 2008; 48: 1312-27.
Keating GM, Santoro A. Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs 2009; 69: 223- 40.
Lau WY, Lai EC. Hepatocellular carcinoma: current management and recent advances. Hepatobiliary Pancreat Dis Int 2008; 7: 237-57.
Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, Nakajima Y, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 1985; 56: 918-28.
A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Li ver Italian Program (CLIP) investigators. Hepatology 1998; 28: 751-5.
Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. The Cancer of the Liver Italian Program (CLIP) Investigators. Hepatology 2000; 31: 840-5.
Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999; 19: 329-38.
Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003; 362: 1907-17.
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003; 37: 429-42.
Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004; 64: 7099-109.
Beeram M, Patnaik A, Rowinsky EK. Raf: a strategic target for therapeutic development against cancer. J Clin Oncol 2005; 23: 6771-90.
Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D, Wilhelm S, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res 2006; 66: 11851-8.
Moore M, Hirte HW, Siu L, Oza A, Hotte SJ, Petrenciuc O, Cihon F, et al. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol 2005; 16: 1688-94.
Awada A, Hendlisz A, Gil T, Bartholomeus S, Mano M, de Valeriola D, Strumberg D et al. Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer 2005; 92: 1855-61.
Strumberg D, Richly H, Hilger RA, Schleucher N, Korfee S, Tewes M, Faghih M, et al. Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol 2005; 23: 965-72.
Clark JW, Eder JP, Ryan D, Lathia C, Lenz HJ. Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43- 9006, in patients with advanced, refractory solid tumors. Clin Cancer Res 2005; 11: 5472-80.
Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006; 24: 4293-300.
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-90.
Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, et 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 Oncol 2009; 10: 25-34.
Alves R, Alves D, Mattos C, Soares S, Harriz M, Vanini H, et al. Safety of sorafenib treatment for intermediate/advanced hepatocellular carcinoma (HCC) in patients with child’s A, B or C: initial results in two experienced centers in Brazil. [abstract no. 1722]. Hepatology 2009; 50(S4): 1101A.
Siegel AB, Cohen EI, Ocean A, Lehrer D, Goldenberg A, Knoxx JJ, Chen H et al. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol 2008; 26: 2992-8.
Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 2003; 21: 2787-99.
Fuchs BC, Fujii T, Dorfman JD, Goodwin JM, Zhu AX, Lanuti M, Tanabe KK. Epithelial-to-mesenchymal transition and integrin- linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Res 2008; 68: 2391-9.