Targeted agents for the systemic treatment of advanced hepatocellular carcinoma

Asia-Pacific Journal of Clinical Oncology

Volumn 5, Issue 2, 2009, Pages 76-86

  Azad, Arun ^a,c   Chionh, Fiona ^a   Cebon, Jonathan ^b  

^a AUSTIN HEALTH   (Australia)

^b LUDWIG INSTITUTE FOR CANCER RESEARCH   (Australia)

^c AUSTIN HOSPITAL   (Australia)

Author keywords

Angiogenesis inhibitor; Hepatocellular carcinoma; Receptor; SHARP; Sorafenib; Vascular endothelial growth factor

Indexed keywords

ALPHA INTERFERON; ALPHA2A INTERFERON; ANGIOGENESIS INHIBITOR; BEVACIZUMAB; CAPECITABINE; CETUXIMAB; CISPLATIN; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; EPIRUBICIN; ERLOTINIB; FLUOROURACIL; GEFITINIB; GEMCITABINE; LAPATINIB; MELANOMA ANTIGEN 3; OCTREOTIDE; OXALIPLATIN; PLACEBO; SORAFENIB; SUNITINIB; TAMOXIFEN; THALIDOMIDE; UFT; UNINDEXED DRUG; VASCULOTROPIN; VIRUS VECTOR;

ADVANCED CANCER; ASCITES; ASTHENIA; BLEEDING; BLOOD TOXICITY; BRAIN DISEASE; CANCER COMBINATION CHEMOTHERAPY; CANCER GENE THERAPY; CANCER HORMONE THERAPY; CANCER IMMUNOTHERAPY; CANCER RESISTANCE; CANCER SURVIVAL; CENTRAL NERVOUS SYSTEM DISEASE; CHEMOEMBOLIZATION; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DIARRHEA; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; HAND FOOT SYNDROME; HUMAN; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LOADING DRUG DOSE; LYMPHOCYTOPENIA; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; NEUTROPENIA; OVERALL SURVIVAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SYSTEMIC THERAPY; THORAX PAIN; THROMBOCYTOPENIA; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; VIRAL GENE DELIVERY SYSTEM;

EID: 66849091820     PISSN: 17437555     EISSN: 17437563     Source Type: Journal    
DOI: 10.1111/j.1743-7563.2009.01202.x     Document Type: Review

References (101)

1. Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: Worldwide incidence and trends. Gastroenterology 2004; 127: S5-16.
2. Sciarrino E, Simonetti RG, Le Moli S, Pagliaro L. Adriamycin treatment for hepatocellular carcinoma. Experience with 109 patients. Cancer 1985; 56: 2751-5.
3. Chlebowski RT, Brzechwa-Adjukiewicz A, Cowden A, Block JB, Tong M, Chan KK. Doxorubicin (75mg/m 2) for hepatocellular carcinoma: Clinical and pharmacokinetic results. Cancer Treat Rep 1984; 68: 487-91.
4. Lai CL, Wu PC, Chan GC, Lok AS, Lin HJ. Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial. Cancer 1988; 62: 479-83.
5. Chuah B, Lim R, Boyer M et al. Multi-centre phase II trial of thalidomide in the treatment of unresectable hepatocellular carcinoma. Acta Oncol 2007; 46: 234-8.
6. van Eeden H, Falkson G, Burger W, Ansell SM. 5-Fluorouracil and leucovorin in hepatocellular carcinoma. Ann Oncol 1992; 3: 404-5.
7. Fuchs CS, Clark JW, Ryan DP et al. A phase II trial of gemcitabine in patients with advanced hepatocellular carcinoma. Cancer 2002; 94: 3186-91.
8. Boige V, Taieb J, Hebbar M et al. Irinotecan as first-line chemotherapy in patients with advanced hepatocellular carcinoma: A multicenter phase II study with dose adjustment according to baseline serum bilirubin level. Eur J Cancer 2006; 42: 456-9.
9. Ikeda M, Okusaka T, Ueno H, Takezako Y, Morizane C. A phase II trial of continuous infusion of 5-fluorouracil, mitoxantrone, and cisplatin for metastatic hepatocellular carcinoma. Cancer 2005; 103: 756-62.
10. Park SH, Lee Y, Han SH et al. Systemic chemotherapy with doxorubicin, cisplatin and capecitabine for metastatic hepatocellular carcinoma. BMC Cancer 2006; 6: 3.
11. Melia WM, Johnson PJ, Williams R. Induction of remission in hepatocellular carcinoma. A comparison of VP 16 with adriamycin. Cancer 1983; 51: 206-10.
12. 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: 3069-75.
13. Llovet JM, Sala M, Castells L et al. Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma. Hepatology 2000; 31: 54-8.
14. Yeo W, Mok TS, Zee B et al. A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst 2005; 97: 1532-8.
15. Tamoxifen in treatment of hepatocellular carcinoma: A randomised controlled trial. CLIP Group (Cancer of the Liver Italian Programme). Lancet 1998; 352: 17-20.
16. Becker G, Allgaier HP, Olschewski M, Zahringer A, Blum HE. Long-acting octreotide versus placebo for treatment of advanced HCC: A randomized controlled double-blind study. Hepatology 2007; 45: 9-15.
17. Coleman MP, Gatta G, Verdecchia A et al. EUROCARE-3 summary: Cancer survival in Europe at the end of the 20th century. Ann Oncol 2003; 14 (Suppl. 5): V128-49.
18. Simonetti RG, Liberati A, Angiolini C, Pagliaro L. Treatment of hepatocellular carcinoma: A systematic review of randomized controlled trials. Ann Oncol 1997; 8: 117-36.
19. Johnson P. Hepatocellular carcinoma: Is current therapy really altering outcome? Gut 2002; 51: 459-62.
20. Ng IO, Liu CL, Fan ST, Ng M. Expression of P-glycoprotein in hepatocellular carcinoma. A determinant of chemotherapy response. Am J Clin Pathol 2000; 113: 355-63.
21. Ng IO. Prognostic significance of pathological and biological factors in hepatocellular carcinoma. J Gastroenterol Hepatol 1998; 13: 666-70.
22. Watanuki A, Ohwada S, Fukusato T et al. Prognostic significance of DNA topoisomerase II alpha expression in human hepatocellular carcinoma. Anticancer Res 2002; 22: 1113-9.
23. Thomas MB. Systemic therapy for hepatocellular carcinoma. Cancer J 2008; 14: 123-7.
24. Kim R. Consensus and controversy in the management of hepatocellular carcinoma. J Am Coll Surg 2007; 205: 108-23.
25. Nagahama H. Predictive factors for tumor response to systemic chemotherapy in patients with hepatocellular carcinoma. Jpn J Clin Oncol 1997; 27: 321-24.
26. Elias L, Crissman HA. Interferon effects upon the adenocarcinoma 38 and HL-60 cell lines: Antiproliferative responses and synergistic interactions with halogenated pyrimidine antimetabolites. Cancer Res 1988; 48: 4868-73.
27. Lai CL, Lau JY, Wu PC et al. Recombinant interferon-alpha in inoperable hepatocellular carcinoma: A randomized controlled trial. Hepatology 1993; 17: 389-94.
28. Obi S, Yoshida H, Toune R et al. Combination therapy of intra-arterial 5-fluorouracil and systemic interferon-alpha for advanced hepatocellular carcinoma with portal venous invasion. Cancer 2006; 106: 1990-7.
29. Nagasue N, Ito A, Yukaya H, Ogawa Y. Estrogen receptors in hepatocellular carcinoma. Cancer 1986; 57: 87-91.
30. Ohnishi S, Murakami T, Moriyama T, Mitamura K, Imawari M. Androgen and estrogen receptors in hepatocellular carcinoma and in the surrounding noncancerous liver tissue. Hepatology 1986; 6: 440-3.
31. Boix L, Bruix J, Castells A et al. Sex hormone receptors in hepatocellular carcinoma. Is there a rationale for hormonal treatment? J Hepatol 1993; 17: 187-91.
32. Chow PK, Tai BC, Tan CK et al. High-dose tamoxifen in the treatment of inoperable hepatocellular carcinoma: A multicenter randomized controlled trial. Hepatology 2002; 36: 1221-6.
33. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003; 37: 429-42.
34. Nowak AK, Stockler MR, Chow PK, Findlay M. Use of tamoxifen in advanced-stage hepatocellular carcinoma. A systematic review. Cancer 2005; 103: 1408-14.
35. Granata OM, Carruba G, Montalto G et al. Altered androgen metabolism eventually leads hepatocellular carcinoma to an impaired hormone responsiveness. Mol Cell Endocrinol 2002; 193: 51-8.
36. Grimaldi C, Bleiberg H, Gay F et al. Evaluation of antiandrogen therapy in unresectable hepatocellular carcinoma: Results of a European Organization for Research and Treatment of Cancer multicentric double-blind trial. J Clin Oncol 1998; 16: 411-7.
37. Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire Randomized trial of leuprorelin and flutamide in male patients with hepatocellular carcinoma treated with tamoxifen. Hepatology 2004; 40: 1361-9.
38. Blaker M, Schmitz M, Gocht A et al. Differential expression of somatostatin receptor subtypes in hepatocellular carcinomas. J Hepatol 2004; 41: 112-8.
39. Yuen MF, Poon RT, Lai CL et al. A randomized placebo-controlled study of long-acting octreotide for the treatment of advanced hepatocellular carcinoma. Hepatology 2002; 36: 687-91.
40. Cebon J, Findlay M, Hargreaves C et al. Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide. Br J Cancer 2006; 95: 853-61.
41. Nicholaou T, Ebert L, Davis ID et al. Directions in the immune targeting of cancer: Lessons learned from the cancer-testis Ag NY-ESO-1. Immunol Cell Biol 2006; 84: 303-17.
42. Boon T, Old LJ. Cancer tumor antigens. Curr Opin Immunol 1997; 9: 681-3.
43. Kariyama K, Higashi T, Kobayashi Y et al. Expression of MAGE-1 and -3 genes and gene products in human hepatocellular carcinoma. Br J Cancer 1999; 81: 1080-7.
44. Kobayashi Y, Higashi T, Nouso K etal. Expression of MAGE, GAGE and BAGE genes in human liver diseases: Utility as molecular markers for hepatocellular carcinoma. J Hepatol 2000; 32: 612-7.
45. Luo G, Huang S, Xie X et al. Expression of cancer-testis genes in human hepatocellular carcinomas. Cancer Immun 2002; 2: 11.
46. Zhang HG, Chen HS, Peng JR et al. Specific CD8(+)T cell responses to HLA-A2 restricted MAGE-A3 p271-279 peptide in hepatocellular carcinoma patients without vaccination. Cancer Immunol Immunother 2007; 56: 1945-54.
47. Zerbini A, Pilli M, Soliani P et al. Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific CD8+cells in patients with hepatocellular carcinoma. J Hepatol 2004; 40: 102-9.
48. Sangro B, Mazzolini G, Ruiz J et al. Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors. J Clin Oncol 2004; 22: 1389-97.
49. Guan M, Rodriguez-Madoz JR, Alzuguren P et al. Increased efficacy and safety in the treatment of experimental liver cancer with a novel adenovirus-alphavirus hybrid vector. Cancer Res 2006; 66: 1620-9.
50. Llovet J, Ricci S, Mazzaferro V etal. Randomized phase III trial of sorafenib versus placebo in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol 2007; 25 (Suppl.): LBA1.
51. 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: 4293-300.
52. Abou-Alfa G, Johnson P, Knox J et al. Final results from a phase II (PhII), randomized, double-blind study of sorafenib plus doxorubicin (S+ D) versus placebo plus doxorubicin (P+D) in patients (pts) with advanced hepatocellular carcinoma (AHCC). Proceedings of the American Society of Clinical Oncology's 2008 Gastrointestinal Cancers Symposium (ASCO GI), January 25-27, 2008, Orlando, Florida: Abstract 128.
53. Shen Y, Shao Y, Hsu C et al. Phase II study of sorafenib plus tegafur/ uracil (UFT) in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol 2008; 26 (Suppl.): Abstract 15664.
54. Del Prete S, Montella L, Addeo R etal. Sorafenib plus long-acting octreotide in advanced hepatocellular carcinoma. Preliminary results of a multicenter ongoing study. J Clin Oncol 2008; 26: (May 20 suppl; Abstract 15624).
55. Faivre SJ, Raymond E, Douillard J etal. Assessment of safety and drug-induced tumor necrosis with sunitinib in patients (pts) with unresectable hepatocellular carcinoma (HCC). J Clin Oncol 2007; 25 (Suppl.): Abstract 3546.
56. Zhu AX, Sahani DV, di Tomaso E et al. A phase II study of sunitinib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2007; 25 (Suppl.): Abstract 4637.
57. Hoda D, Catherine C, Strosberg J et al. Phase II study of sunitinib malate in adult pts (pts) with metastatic or surgically unresectable hepatocellular carcinoma (HCC). Proceedings of the American Society of Clinical Oncology's 2008 Gastrointestinal Cancers Symposium (ASCO GI), January 25-27, 2008, Orlando, Florida: Abstract 267.
58. Schwartz JD, Schwartz M, Lehrer D et al. Bevacizumab in unresectable hepatocellular carcinoma (HCC) for patients without metastasis and without invasion of the portal vein. J Clin Oncol 2006; 24 (Suppl.): Abstract 4144.
59. Malka D, Dromain C, Farace F et al. Bevacizumab in patients (pts) with advanced hepatocellular carcinoma (HCC): Preliminary results of a phase II study with circulating endothelial cell (CEC) monitoring. J Clin Oncol 2007; 25 (Suppl.): Abstract 4570.
60. 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: 1898-903.
61. Sun W, Haller DG, Mykulowycz K et al. Combination of capecitabine, oxaliplatin with bevacizumab in treatment of advanced hepatocellular carcinoma (HCC): A phase II study. J Clin Oncol 2007; 25 (Suppl.): Abstract 4574.
62. Hsu C, Yang T, Hsu C et al. Phase II study of bevacizumab (A) plus capecitabine (X) in patients (pts) with advanced/metastatic hepatocellular carcinoma (HCC): Final report. J Clin Oncol 2008; 26 (Suppl.): Abstract 4603.
63. Thomas MB, Chadha R, Iwasaki M, Glover K, Abbruzzese JL. The combination of bevacizumab (B) and erlotinib (E) shows significant biological activity in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol 2007; 25 (Suppl.): Abstract 4567.
64. Philip PA, Mahoney MR, Allmer C et al. Phase II study of erlotinib in patients with advanced biliary cancer. J Clin Oncol 2006; 24: 3069-74.
65. Thomas MB, Chadha R, Glover K et al. Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma. Cancer 2007; 110: 1059-67.
66. O'Dwyer PJ, Giantonio BJ, Levy DE et al. Gefitinib in advanced unresectable hepatocellular carcinoma: Results from the Eastern Cooperative Oncology Group's Study E1203. J Clin Oncol 2006; 24 (Suppl.): Abstract 4143.
67. Ramanathan RK, Belani CP, Singh DA et al. Phase II study of lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase 1 and 2 (Her2/Neu) in patients (pts) with advanced biliary tree cancer (BTC) or hepatocellular cancer (HCC). A California Consortium (CCC-P) Trial. J Clin Oncol 2006; 24 (Suppl.): Abstract 4010.
68. Zhu AX, Stuart K, Blaszkowsky LS et al. Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma. Cancer 2007; 110: 581-9.
69. Gruenwald V, Wilkens L, Gebel M etal. A phase II open-label study of cetuximab in unresectable hepatocellular carcinoma: Final results. J Clin Oncol 2007; 25 (Suppl.): Abstract 4598.
70. Louafi S, Hebbar M, Rosmorduc O et al. Gemcitabine, oxaliplatin (GEMOX) and cetuximab for treatment of hepatocellular carcinoma (HCC): Results of the phase II study ERGO. J Clin Oncol 2007; 25 (Suppl.): 4594.
71. Miura H, Miyazaki T, Kuroda M et al. Increased expression of vascular endothelial growth factor in human hepatocellular carcinoma. J Hepatol 1997; 27: 854-61.
72. Suzuki K, Hayashi N, Miyamoto Y et al. Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma. Cancer Res 1996; 56: 3004-9.
73. Hisaka T, Yano H, Haramaki M, Utsunomiya I, Kojiro M. Expressions of epidermal growth factor family and its receptor in hepatocellular carcinoma cell lines: Relationship to cell proliferation. Int J Oncol 1999; 14: 453-60.
74. Fang J, Richardson B. The MAPK signalling pathways and colorectal cancer. Lancet Oncol 2005; 6: 322-27.
75. Liu L, Cao Y, Chen C 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.
76. Mendez-Sanchez N, Vasquez-Fernandez F, Zamora-Valdes D, Uribe M. Sorafenib, a systemic therapy for hepatocellular carcinoma. Ann Hepatol 2008; 7: 46-51.
77. Abou-Alfa G, 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 (Suppl.): Abstract 4518.
78. Raoul J, Santoro A, Beaugrand M et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to ECOG performance status: A subanalysis from the SHARP trial. J Clin Oncol 2008; 26 (Suppl.): Abstract 4587.
79. Cheng A, Kang Y, Chen Z et al. Randomized phase III trial of sorafenib versus placebo in Asian patients with advanced hepatocellular carcinoma. J Clin Oncol 2008; 26 (Suppl.): Abstract 4509.
80. BHaO P. Nexavar significantly improved overall survival in phase III Asia-Pacific liver cancer trial. Press release August 27, 2007.
81. Cabrera R, George T, Soldevila-Pico C, Firpi R, Morelli G, Nelson DR. Safety of sorafenib alone or in combination with locoregional therapy in patients with advanced hepatocellular carcinoma (HCC) and decompensated cirrhosis. Proceedings of the American Society of Clinical Oncology's 2008 Gastrointestinal Cancers Symposium; 25-27 January 2008, Orlando, Florida. ASCO, Alexandria 2008: Abstract 147.
82. Zhu A. Development of sorafenib and other molecularly targeted agents in hepatocellular carcinoma. Cancer 2008; 112: 250-9.
83. D'Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994; 91: 4082-5.
84. Lin AY, Brophy N, Fisher GA et al. Phase II study of thalidomide in patients with unresectable hepatocellular carcinoma. Cancer 2005; 103: 119-25.
85. Patt YZ, Hassan MM, Lozano RD et al. Thalidomide in the treatment of patients with hepatocellular carcinoma: A phase II trial. Cancer 2005; 103: 749-55.
86. Zhu AX, Fuchs CS, Clark JW et al. A phase II study of epirubicin and thalidomide in unresectable or metastatic hepatocellular carcinoma. Oncologist 2005; 10: 392-8.
87. Schwartz JD, Sung M, Schwartz M et al. Thalidomide in advanced hepatocellular carcinoma with optional low-dose interferon-alpha2a upon progression. Oncologist 2005; 10: 718-27.
88. Wu WZ, Sun HC, Shen YF et al. Interferon alpha 2a down-regulates VEGF expression through PI3 kinase and MAP kinase signaling pathways. J Cancer Res Clin Oncol 2005; 131: 169-78.
89. O'Neil BH, Bernard SA, Goldberg RM et al. Phase II study of oxaliplatin, capecitabine, and cetuximab in advanced hepatocellular carcinoma. J Clin Oncol 2008; 26(Suppl.): Abstract 4604.
90. Marone R, Cmiljanovic V, Giese B, Wymann MP. Targeting phosphoinositide 3-kinase: Moving towards therapy. Biochim Biophys Acta 2008; 1784: 159-85.
91. Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol 2008; 48 (Suppl. 1): S20-37.
92. Villanueva A, Chiang DY, Newell P et al. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 2008; 135: 1972-83.
93. Bu X, Le C, Jia F et al. Synergistic effect of mTOR inhibitor rapamycin and fluorouracil in inducing apoptosis and cell senescence in hepatocarcinoma cells. Cancer Biol Ther 2008; 7: 392-6.
94. Piguet AC, Semela D, Keogh A et al. Inhibition of mTOR in combination with doxorubicin in an experimental model of hepatocellular carcinoma. J Hepatol 2008; 49: 78-87.
95. Tam KH, Yang ZF, Lau CK, Lam CT, Pang RW, Poon RT. Inhibition of mTOR enhances chemosensitivity in hepatocellular carcinoma. Cancer Lett 2009; 273: 201-9.
96. Rodon J, DeSantos V, Ferry RJ Jr, Kurzrock, R. Early drug development of inhibitors of the insulin-like growth factor-I receptor pathway: Lessons from the first clinical trials. Mol Cancer Ther 2008; 7: 2575-88.
97. Hopfner M, Huether A, Sutter AP, Baradari V, Schuppan D, Scherubl H. Blockade of IGF-1 receptor tyrosine kinase has anti-neoplastic effects in hepatocellular carcinoma cells. Biochem Pharmacol 2006; 71: 1435-48.
98. Takami T, Kaposi-Novak P, Uchida K et al. Loss of hepatocyte growth factor/c-Met signaling pathway accelerates early stages of N-nitrosodiethylamine induced hepatocarcinogenesis. Cancer Res 2007; 67: 9844-51.
99. Ryder S. Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults. Gut 2003; 52: 1-8.
100. Therasse P, Arbuck SG, Eisenhauer EA etal. 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 2000; 92: 205-16.
101. DePrimo SE, Cheng A, Lanzalone S etal. Circulating biomarkers of sunitinib in patients with unresectable hepatocellular carcinoma (HCC): analysis of correlations with outcome and tumor imaging parameters. J Clin Oncol 2008; 26 (Suppl.): Abstract 4593.