Molecular targeted therapy of advanced hepatocellular carcinoma beyond sorafenib

Expert Opinion on Pharmacotherapy

Volumn 11, Issue 13, 2010, Pages 2187-2198

  Yau, Thomas ^a   Pang, Roberta ^a   Chan, Pierre ^a   Poon, Ronnie T ^a  

^a UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

Angiogenesis; Chemotherapy; Hepatocellular carcinoma; Molecular targeted therapy

Indexed keywords

1 [4 (3 AMINO 1H INDAZOL 4 YL)PHENYL] 3 (2 FLUORO 5 METHYLPHENYL)UREA; 2,4 DIMETHYL 5 (2 OXO 1H INDOL 3 YLMETHYLENE) 3 PYRROLEPROPIONIC ACID; APC PROTEIN; BEVACIZUMAB; BRIVANIB ALANINATE; CAPECITABINE; CEDIRANIB; CETUXIMAB; CYCLIN D1; DOXORUBICIN; ERLOTINIB; EVEROLIMUS; FLUOROPYRIMIDINE; GEFITINIB; GEMCITABINE; MITOGEN ACTIVATED PROTEIN KINASE; OCTREOTIDE; OXALIPLATIN; PAZOPANIB; PLACEBO; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN P73; RAF PROTEIN; SOMATOMEDIN; SORAFENIB; SUNITINIB; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3; VATALANIB; XL 880;

ADVANCED CANCER; ANOREXIA; CANCER COMBINATION CHEMOTHERAPY; CLINICAL TRIAL; DRUG MECHANISM; DRUG TARGETING; DRUG WITHDRAWAL; FATIGUE; HUMAN; HYPERTENSION; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; MOLECULAR THERAPY; NEUTROPENIA; ONCOGENE C MYC; REVIEW; THROMBOCYTOPENIA;

ADULT; ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BENZENESULFONATES; CARCINOMA, HEPATOCELLULAR; CLINICAL TRIALS AS TOPIC; DISEASE PROGRESSION; FEMALE; HUMANS; LIVER NEOPLASMS; MALE; MOLECULAR TARGETED THERAPY; PROTEIN KINASE INHIBITORS; PYRIDINES; TREATMENT OUTCOME;

EID: 77955817977     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656561003724705     Document Type: Review

References (88)

1. Hussain SA, Ferry DR, El-Gazzaz G, et al. Hepatocellular carcinoma. Ann Oncol 2001;12(2):161-172
2. El-Serag HB, Davila JA, Petersen NJ, McGlynn KA. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 2003;139(10):817-823
3. El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999;340(10):745-750
4. Caldwell SH, Crespo DM, Kang HS, Al-Osaimi AM. Obesity and hepatocellular carcinoma. Gastroenterology 2004;127(5 Suppl 1):S97-103
5. Fan ST, Lo CM, Liu CL, et al. Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths. Ann Surg 1999;229(3):322-330
6. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003;37(2):429-442
7. Palmer DH, Hussain SA, Johnson PJ. Systemic therapies for hepatocellular carcinoma. Expert Opin Investig Drugs 2004;13(12):1555-1568
8. Gish RG, Porta C, Lazar L, et al. Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin. J Clin Oncol 2007;25(21):3069-3075
9. Greten TF, Korangy F, Manns MP, Malek NP. Molecular therapy for the treatment of hepatocellular carcinoma. Br J Cancer 2009;100(1):19-23
10. Theise ND, Yao JL, Harada K, et al. Hepaticstem cellmalignancies in adults: four cases. Histopathology 2003;43(3):263-271
11. Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 2002;31(4):339-346
12. Feitelson MA, Sun B, Satiroglu Tufan NL, et al. Genetic mechanisms of hepatocarcinogenesis. Oncogene 2002;21(16):2593-2604
13. Pang RW, Joh JW, Johnson PJ, et al. Biology of hepatocellular carcinoma. Ann Surg Oncol 2008;15(4):962-971
14. Epstein RJ, Leung TW. Reversing hepatocellular carcinoma progression by using networked biological therapies. Clin Cancer Res 2007;13(1):11-17
15. Yang B, Guo M, Herman JG, Clark DP. Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma. Am J Pathol 2003;163(3):1101-1107
16. Pang R, Poon RT. Angiogenesis and antiangiogenic therapy in hepatocellular carcinoma. Cancer Lett 2006;242(2):151-167
17. Lee JS, Heo J, Libbrecht L, et al. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 2006;12(4):410-416
18. Wilhelm SM, Carter C, Tang L, 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(19):7099-7109
19. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359(4):378-390
20. Cheng AL, Kang YK, Chen Z, 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(1):25-34
21. Hsu C, Shen YC, Cheng CC, et al. Geographic difference in survival outcome for advanced hepatocellular carcinoma: implications on future clinical trial design. Contemp Clin Trials 2010;31(1):55-61
22. Abou-Alfa GK, Amadori D, Santoro A, et al. Is sorafenib (S) safe and effective in patients (pts) with hepatocellular carcinoma (HCC) and Child-Pugh B (CPB) cirrhosis? J Clin Oncol 2008;26(20 Suppl):abstract 4518
23. Llovet JM, Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology 2008;48(4):1312-1327
24. Abou-Alfa GK, Schwartz L, Ricci S, et al. Preliminary results from a phase II, randomized, double-blind study of sorafenib plus doxorubicin versus placebo plus doxorubicin in patients with advanced hepatocellular carcinoma. In: ECCO (European Journal of Cancer Supplements, Barcelona) 2007. p. 259
25. Yau T, Chan P, Cheung FY, et al. Phase II trial of sorafenib with capecitabine and oxaliplatin (SECOX) in patients with locally advanced or metastatic hepatocellular carcinoma. In: Joint ECCO 15-34th ESMO Multidisciplinary Congress (European Journal of Cancer Supplements, Berlin) 2009. p. 1-24
26. Prete SD, Montella L, Caraglia M, et al. Sorafenib plus octreotide is an effective and safe treatment in advanced hepatocellular carcinoma: multicenter phase II So.LAR. study. Cancer Chemother Pharmacol 2009
27. Pang RW, Poon RT. From molecular biology to targeted therapies for hepatocellular carcinoma: the future is now. Oncology 2007;72(Suppl 1):30-44
28. Miura H, Miyazaki T, Kuroda M, et al. Increased expression of vascular endothelial growth factor in human hepatocellular carcinoma. J Hepatol 1997;27(5):854-861 (Pubitemid 27454829)
29. Griffiths L, Stratford IJ. Platelet-derived endothelial cell growth factor thymidine phosphorylase in tumour growth and response to therapy. Br J Cancer 1997;76(6):689-693
30. Asahara T, Bauters C, Zheng LP, et al. Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo. Circulation 1995;92(9 Suppl):II365-371
31. Zhang ZL, Liu ZS, Sun Q. Expression of angiopoietins, Tie2 and vascular endothelial growth factor in angiogenesis and progression of hepatocellular carcinoma. World J Gastroenterol 2006;12(26):4241-4245
32. Chow NH, Hsu PI, Lin XZ, et al. Expression of vascular endothelial growth factor in normal liver and hepatocellular carcinoma: an immunohistochemical study. Hum Pathol 1997;28(6):698-703
33. Epstein RJ. VEGF signaling inhibitors: more pro-apoptotic than anti-angiogenic. Cancer Metastasis Rev 2007;26(3-4):443-452
34. Presta LG, Chen H, OConnor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997;57(20):4593-4599
35. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001;7(9):987-989
36. Siegel AB, Cohen EI, Ocean A, et al. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol 2008;26(18):2992-2998
37. Zhu AX, Blaszkowsky LS, Ryan DP, et al. Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006;24(12):1898-1903
38. Thomas MB, Morris JS, Chadha R, et al. Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma. J Clin Oncol 2009;27(6):843-850
39. Kaseb AO, Iwasaki M, Javle M, et al. Biological activity of bevacizumab and erlotinib in patients with advanced hepatocellular carcinoma (HCC). In: 2009 ASCO Annual Meeting. J Clin Oncol Chicago 2009
40. Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003;9(1):327-337
41. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356(2):115-124
42. Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006;368(9544):1329- 1338
43. Zhu AX, Sahani DV, Duda DG, et al. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol 2009;27(18):3027-3035
44. Faivre S, Raymond E, Boucher E, et al. Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study. Lancet Oncol 2009;10(8):794-800
45. Koeberle D, Montemurro M, Samaras P, et al. Continuous sunitinib treatment in patients with unresectable hepatocellular carcinoma (HCC): a multicenter phase II trial (SAKK 77/06 and SASL 23). In: ASCO (Orlando, 2009)
46. Wood JM, Bold G, Buchdunger E, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 2000;60(8):2178-2189
47. Liu Y, Poon RT, Li Q, et al. Both antiangiogenesis-and angiogenesis-independent effects are responsible for hepatocellular carcinoma growth arrest by tyrosine kinase inhibitor PTK787/ZK222584. Cancer Res 2005;65(9):3691-3699
48. Koch I, Baron A, Roberts S, et al. Influence of hepatic dysfunction on safety, tolerability, and pharmacokinetics (PK) of PTK787/ZK 222584 in patients (Pts) with unresectable hepatocellular carcinoma (HCC). In: 2005 ASCO Annual Meeting Proceedings. (Journal of Clinical Oncology, Orlando) No 16S (June 11 Supplement), 2005:4134
49. Yau T, Chan P, Ng KK, et al. Phase I/II Trial of PTK787 /ZK222584 Combined with Intravenous Doxorubicin for Treatment of Patients with Advanced Hepatocellular Carcinoma (HCC): Implication for Anti-angiogenic Approach To HCC. Cancer 2010. (In Press)
50. Kohne CEB, Lin E, Valle JW, et al. Final results of CONFIRM 2: a multinational, randomized, double-blind, phase III study in 2nd line patients (pts) with metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo. In: ASCO (Chicago, 2007)
51. Hecht JR, Trarbach T, Jaeger E, et al. Final overall survival results of CONFIRM 1, a randomized, double-blind, placebo-controlled phase III trial inpatients with metastatic adenocarcinoma of the colon or rectum receiving first line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin (FOLFOX 4) and PTK787/ZK 222584 (PTK/ZK) or placebo. Euro J Cancer 2007;5(4 Suppl):3010
52. Presta M, DellEra P, Mitola S, et al. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 2005;16(2):159-178
53. Uematsu S, Higashi T, Nouso K, et al. Altered expression of vascular endothelial growth factor, fibroblast growth factor-2 and endostatin in patients with hepatocellular carcinoma. J Gastroenterol Hepatol 2005;20(4):583-588
54. Raoul JL, Finn RS, Kang YK, et al. An open-label phase II study of first-and second-line treatment with brivanib in patients with hepatocellular carcinoma (HCC). In: ASCO (Chicago, 2009)
55. Yau CC, Chen PJ, Curtis CM, et al. A phase I study of pazopanib in patients with advanced hepatocellular carcinoma. In: ASCO (Chicago, 2009)
56. Toh H, Chen P, Carr BI, et al. A phase II study of ABT-869 in hepatocellular carcinoma (HCC): Interim analysis. In: ASCO (Chicago, 2009)
57. Kanai F, Yoshida H, Tateishi R, et al. TSU-68 HCC study group Final result of a phase I/II trial of the oral anti-angiogenesis inhibitor TSU-68 in patients with advanced hepatocellular carcinoma. In: ASCO (Chicago, 2008)
58. Alberts SR, Morlan BW, Kim GP, et al. NCCTG phase II trial (N044J) of AZD2171 for patients with hepatocellular carcinoma (HCC)-Interim review of toxicity. In: GI ASCO (Orlando, 2007)
59. Ito Y, Takeda T, Sakon M, et al. Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma. Br J Cancer 2001;84(10):1377-1383 (Pubitemid 32522107)
60. Yeh YC, Tsai JF, Chuang LY, et al. Elevation of transforming growth factor alpha and its relationship to the epidermal growth factor and alpha-fetoprotein levels in patients with hepatocellular carcinoma. Cancer Res 1987;47(3):896-901
61. Kiss A, Wang NJ, Xie JP, Thorgeirsson SS. Analysis of transforming growth factor (TGF)-alpha/epidermal growth factor receptor, hepatocyte growth Factor/c-met, TGF-beta receptor type II, and p53 expression in human hepatocellular carcinomas. Clin Cancer Res 1997;3(7):1059-1066
62. Yamaguchi K, Carr BI, Nalesnik MA. Concomitant and isolated expression of TGF-alpha and EGF-R in human hepatoma cells supports the hypothesis of autocrine, paracrine, and endocrine growth of human hepatoma. J Surg Oncol 1995;58(4):240-245
63. Zhu AX, Stuart K, Blaszkowsky LS, et al. Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma. Cancer 2008;15(12):2733-2739
64. Asnacios A, Fartoux L, Romano O, et al. Gemcitabine plus oxaliplatin (GEMOX) combined with cetuximab in patients with progressive advanced stage hepatocellular carcinoma: results of a multicenter phase 2 study. Cancer 2008;112(12):2733-2739
65. Philip PA, Mahoney MR, Allmer C, et al. Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer. J Clin Oncol 2005;23(27):6657-6663
66. Thomas MB, Chadha R, Glover K, et al. Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma. Cancer 2007;110(5):1059- 1067
67. ODwyer PJ, Giantonio BJ, Levy DE, et al. Gefitinib in advanced unresectable hepatocellular carcinoma: results from the Eastern Cooperative Oncology Groups Study E1203. 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition). J Clin Oncol 2006;24(18S):4143
68. Bekaii-Saab T, Markowitz J, Prescott N, et al. A multi-institutional phase II study of the efficacy and tolerability of lapatinib in patients with advanced hepatocellular carcinomas. Clin Cancer Res 2009;15(18):5895-5901
69. Hsu C, Huang CL, Hsu HC, et al. HER-2/neu overexpression is rare in hepatocellular carcinoma and not predictive of anti-HER-2/neu regulation of cell growth and chemosensitivity. Cancer 2002;94(2):415-420
70. Heinze T, Jonas S, Karsten A, Neuhaus P. Determination of the oncogenes p53 and C-erb B2 in the tumour cytosols of advanced hepatocellular carcinoma (HCC) and correlation to survival time. Anticancer Res 1999;19(4A):2501-2503
71. Su Q, Liu Y. Expression of c-erbB-2 protein and EGF receptor in hepatitis B, cirrhosis and hepatocellular carcinoma. Zhonghua Bing Li Xue Za Zhi 1995;24(2):93-95
72. Rusnak DW, Lackey K, Affleck K, et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther 2001;1(2):85-94
73. Fingar DC, Richardson CJ, Tee AR, et al. mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E. Mol Cell Biol 2004;24(1):200-216
74. Schmitz KJ, Wohlschlaeger J, Lang H, et al. Activation of the ERK and AKT signalling pathway predicts poor prognosis in hepatocellular carcinoma and ERK activation in cancer tissue is associated with hepatitis C virus infection. J Hepatol 2008;48(1):83-90
75. Villanueva A, Chiang DY, Newell P, et al. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 2008;135(6):1972-1983, 1983 e1971-1911
76. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372(9637):449-456
77. Michalopoulos GK, DeFrances MC. Liver regeneration. Science 1997;276(5309):60-66
78. Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. Met, metastasis, motility and more. Nat Rev Mol Cell Biol 2003;4(12):915-925
79. Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factors and neoplasia. Nat Rev Cancer 2004;4(7):505-518
80. Marotta F, Vangieri B, Cecere A, Gattoni A. The pathogenesis of hepatocellular carcinoma is multifactorial event. Novel immunological treatment in prospect. Clin Ther 2004;155(5):187-199
81. Wong CM, Ng IO. Molecular pathogenesis of hepatocellular carcinoma. Liver Int 2008;28(2):160-174
82. Sun S, Lee NP, Poon RT, et al. Oncoproteomics of hepatocellular carcinoma: from cancer markers discovery to functional pathways. Liver Int 2007;27(8):1021-1038
83. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100(1):57-70
84. Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008;359(17):1757-1765
85. Abou-Alfa GK, Schwartz L, Ricci S, et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006;24(26):4293-4300
86. Abou-Alfa GK, Letourneau R, Harker G, et al. Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. J Clin Oncol 2006;24(27):4441-4447
87. Llovet J, Pena C, Shan M, et al. Biomarkers predicting outcome of patients with hepatocellular carcinoma: results from the randomised phase III SHARP trial. In: AASLD 59th annual meeting 2008
88. Yau T, Chan P, Epstein R, Poon RT. Management of advanced hepatocellular carcinoma in the era of targeted therapy. Liver Int 2009;29(1):10-17