Systemic therapy for advanced hepatocellular carcinoma: A review

European Journal of Cancer

Volumn 40, Issue 10, 2004, Pages 1474-1484

  Nowak, Anna K ^a   Chow, Pierce K H ^b   Findlay, Michael ^c  

^a UNIVERSITY OF SYDNEY   (Australia)

^b SINGAPORE GENERAL HOSPITAL   (Singapore)

^c UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

Antineoplastic agents; Antineoplastic combined chemotherapy protocols; Carcinoma; Combination; Drug therapy; Hepatocellular; Hormonal; Immunotherapy; Liver neoplasms

Indexed keywords

5 ETHYNYLURACIL; ANTHRACYCLINE; ANTINEOPLASTIC AGENT; BETA INTERFERON; CARMOFUR; CISPLATIN; CLOFAZIMINE; DAUNORUBICIN; DOXORUBICIN; EPIRUBICIN; ETOPOSIDE; FLUOROPYRIMIDINE; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; HORMONE; HYDROXYUREA; IDARUBICIN; IMMUNOLOGIC AGENT; LIPOSOME; LOMUSTINE; MENOGARIL; MITOMYCIN C; MITOXANTRONE; PRODRUG; STREPTOZOCIN; TAMOXIFEN; TEGAFUR; UNINDEXED DRUG; URACIL;

ADVANCED CANCER; BLOOD TOXICITY; CANCER CHEMOTHERAPY; CANCER MORTALITY; CANCER SURVIVAL; CLINICAL TRIAL; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG FORMULATION; DRUG MECHANISM; HEALTH CENTER; HEPATITIS B; HEPATITIS C; HORMONAL THERAPY; HUMAN; HYPERBILIRUBINEMIA; IMMUNOTHERAPY; LIVER CELL CARCINOMA; LOW DRUG DOSE; META ANALYSIS; PRIORITY JOURNAL; REVIEW; SYSTEMIC THERAPY; TOXICITY; TREATMENT OUTCOME;

EID: 2942513114     PISSN: 09598049     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejca.2004.02.027     Document Type: Article

References (174)

1. Ferlay J, Bray F, Pisani P, Parkin DM. In: GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide. Version 1.0 ed. IARC Cancer Base No. 5. Lyon: IARC Press; 2001
2. Bosch F. Global epidemiology of hepatocellular carcinoma. Liver cancer. 1997;13-28 Churchill Livingstone, New York
3. Yang H.I., Lu S.N., Liaw Y.F., et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. NEJM. 347(3):2002;168-174
4. Tsukuma H., Hiyama T., Tanaka S., et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. NEJM. 328(25):1993;1797- 1801
5. El-Serag H.B., Mason A.C. Rising incidence of hepatocellular carcinoma in the United States. NEJM. 340(10):1999;745-750
6. Colombo M., Kuo G., Choo Q.L., et al. Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. Lancet. 2(8670):1989;1006-1008
7. Fong Y., Sun R.L., Jarnagin W., Blumgart L.H. An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann. Surg. 229(6):1999;790-799. [discussion 799-800]
8. Johnson P.J. Hepatocellular carcinoma: is current therapy really altering outcome. Gut. 51(4):2002;459-462
9. Groupe d'Etude et de Traitment du Carcinome Hepatocellulaire. A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. NEJM 1995;332(19):1256-61
10. Balsells J., Charco R., Lazaro J.L., et al. Resection of hepatocellular carcinoma in patients with cirrhosis. Br. J. Surg. 83(6):1996;758-761
11. Llovet J.M., Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 37(2):2003;429-442
12. Chan E.S.-Y., Chow P.K.-H., Tai B.-C., Machin D., Soo K.-C. Neoadjuvant and adjuvant therapy for operable hepatocellular carcinoma (Cochrane Review). The Cochrane Library. 2003;John Wiley & Sons, Ltd. Chichester, UK
13. Mathurin P., Raynard B., Dharancy S., et al. Meta-analysis: evaluation of adjuvant therapy after curative liver resection for hepatocellular carcinoma. Aliment. Pharmacol. Ther. 17(10):2003;1247-1261
14. Huang C.C., Wu M.C., Xu G.W., et al. Overexpression of the MDR1 gene and P-glycoprotein in human hepatocellular carcinoma. J. Natl. Cancer Inst. 84(4):1992;262-264
15. Chou Y.Y., Cheng A.L., Hsu H.C. Expression of P-glycoprotein and p53 in advanced hepatocellular carcinoma treated by single agent chemotherapy: clinical correlation. J. Gastroeterol. Hepatol. 12(8):1997;569-575
16. Olweny C.L., Toya T., Katongole-Mbidde E., Mugerwa J., Kyalwazi S.K., Cohen H. Treatment of hepatocellular carcinoma with adriamycin. Preliminary communication. Cancer. 36(4):1975;1250-1257
17. Vogel C.L., Bayley A.C., Brooker R.J., Anthony P.P., Ziegler J.L. A phase II study of adriamycin (NSC 123127) in patients with hepatocellular carcinoma from Zambia and the United States. Cancer. 39(5):1977;1923-1929
18. Johnson P.J., Williams R., Thomas H., Sherlock S., Murray-Lyon I.M. Induction of remission in hepatocellular carcinoma with doxorubicin. Lancet. 1(8072):1978;1006-1009
19. Oon C.J., Chua E.J., Foong W.C., et al. Adriamycin in the treatment of resectible and irresectible primary hepatocellular carcinoma. Ann. Acad. Med. Singapore. 9(2):1980;256-259
20. Falkson G., Moertel C.G., Lavin P., Pretorius F.J., Carbone P.P. Chemotherapy studies in primary liver cancer: a prospective randomized clinical trial. Cancer. 42(5):1978;2149-2156
21. Choi T.K., Lee N.W., Wong J. Chemotherapy for advanced hepatocellular carcinoma. Adriamycin versus quadruple chemotherapy. Cancer. 53(3):1984;401-405
22. Melia W.M., Johnson P.J., Williams R. Induction of remission in hepatocellular carcinoma. A comparison of VP 16 with adriamycin. Cancer. 51(2):1983;206-210
23. 2) for hepatocellular carcinoma: clinical and pharmacokinetic results. Cancer Treat. Rep. 68(3):1984;487-491
24. Sciarrino E., Simonetti R.G., Le Moli S., Pagliaro L. Adriamycin treatment for hepatocellular carcinoma Experience with 109 patients. Cancer. 56(12):1985;2751-2755
25. Johnson P.J., Dobbs N., Kalayci C., et al. Clinical efficacy and toxicity of standard dose adriamycin in hyperbilirubinaemic patients with hepatocellular carcinoma: relation to liver tests and pharmacokinetic parameters. Br. J. Cancer. 65(5):1992;751-755
26. Colombo M., Tommasini M.A., Del Ninno E., Rumi M.G., De Fazio C., Dioguardi M.L. Hepatocellular carcinoma in Italy: report of a clinical trial with intravenous doxorubicin. Liver. 5(6):1985;336-341
27. Lai C.L., Wu P.C., Chan G.C., Lok A.S., Lin H.J. Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial. Cancer. 62(3):1988;479-483
28. Mathurin P., Rixe O., Carbonell N., et al. Review article: overview of medical treatments in unresectable hepatocellular carcinoma - an impossible meta-analysis. Aliment. Pharmacol. Ther. 12(2):1998;111-126
29. Cheng A.L., Yeh K.H., Fine R.L., et al. Biochemical modulation of doxorubicin by high-dose tamoxifen in the treatment of advanced hepatocellular carcinoma. Hepatogastroenterology. 45(24):1998;1955-1960
30. Schachschal G., Lochs H., Plauth M. Controlled clinical trial of doxorubicin and tamoxifen versus tamoxifen monotherapy in hepatocellular carcinoma. Eur. J. Gastroenterol. Hepatol. 12(3):2000;281-284
31. Hong R.L., Tseng Y.L. A phase II and pharmacokinetic study of pegylated liposomal doxorubicin in patients with advanced hepatocellular carcinoma. Cancer Chemother. Pharmacol. 51(5):2003;433-438
32. Daniele B., De Vivo R., Perrone F., et al. Phase I clinical trial of liposomal daunorubicin in hepatocellular carcinoma complicating liver cirrhosis. Anticancer Res. 20(2B):2000;1249-1251
33. Halm U., Etzrodt G., Schiefke I., et al. A phase II study of pegylated liposomal doxorubicin for treatment of advanced hepatocellular carcinoma. Ann. Oncol. 11(1):2000;113-114
34. Schmidinger M., Wenzel C., Locker G.J., et al. Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma. Br. J. Cancer. 85(12):2001;1850-1852
35. Yeo W., Chan K.K., Mukwaya G., et al. Phase II studies with DaunoXome in patients with nonresectable hepatocellular carcinoma: clinical and pharmacokinetic outcomes. Cancer Chemother. Pharmacol. 44(2):1999;124-130
36. Ruff P., Moodley S.D., Rapoport B.L., Vorobiof D.A., Maart K., Chasen M.R. Long term follow-up of pegylated liposomal doxorubicin (Caelyx): a well tolerated and effective agent in advanced hepatocellular carcinoma (HCC. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 20:2001;. [Abstract 667]
37. Morstyn G., Ihde D.C., Eddy J.L., Bunn P.A., Cohen M.H., Minna J.D. Combination chemotherapy of hepatocellular carcinoma with doxorubicin and streptozotocin. Am. J. Clin. Oncol. 6(5):1983;547-551
38. Chlebowski R.T., Chan K.K., Tong M.J., Weiner J.M., Ryden V.M., Bateman J.R. Adriamycin and methyl-CCNU combination therapy in hepatocellular carcinoma: clinical and pharmacokinetic aspects. Cancer. 48(5):1981;1088-1095
39. Falkson C.I., Falkson G. A phase II evaluation of clofazimine plus doxorubicin in advanced, unresectable primary hepatocellular carcinoma. Oncology. 57(3):1999;232-235
40. Yang T.S., Wang C.H., Hsieh R.K., Chen J.S., Fung M.C. Gemcitabine and doxorubicin for the treatment of patients with advanced hepatocellular carcinoma: a phase I-II trial. Ann. Oncol. 13(11):2002;1771-1778
41. ′ -Epidoxorubicin (Epirubicin) as a single agent in advanced primary hepatocellular carcinoma - a preliminary experience Ann. Acad. Med. Singapore. 15(2):1986;169-171
42. ′ -Epidoxorubicin (epirubicin): activity in hepatocellular carcinoma J. Clin. Oncol. 3(11):1985;1535-1540
43. Pohl J., Zuna I., Stremmel W., Rudi J. Systemic chemotherapy with epirubicin for treatment of advanced or multifocal hepatocellular carcinoma. Chemotherapy. 47(5):2001;359-365
44. Raderer M., Pidlich J., Muller C., et al. A phase I/II trial of epirubicin and high dose tamoxifen as a potential modulator of multidrug resistance in advanced hepatocellular carcinoma. Eur. J. Cancer. 32A(13):1996;2366-2368
45. Bobbio-Pallavicini E., Porta C., Moroni M., et al. Epirubicin and etoposide combination chemotherapy to treat hepatocellular carcinoma patients: a phase II study. Eur. J. Cancer. 33(11):1997;1784-1788
46. Huang Y.H., Wu J.C., Lui W.Y., et al. Prospective case-controlled trial of adjuvant chemotherapy after resection of hepatocellular carcinoma. World J. Surg. 24(5):2000;551-555
47. Lai E.C., Lo C.M., Fan S.T., Liu C.L., Wong J. Postoperative adjuvant chemotherapy after curative resection of hepatocellular carcinoma: a randomized controlled trial. Arch. Surg. 133(2):1998;183-188
48. Dunk A.A., Scott S.C., Johnson P.J., Melia W., Lok A.S., Murray-Lyon I., et al. Mitozantrone as single agent therapy in hepatocellular carcinoma. A phase II study. J. Hepatol. 1(4):1985;395-404
49. Colleoni M., Nole F., Di Bartolomeo M., de Braud F., Bajetta E. Mitoxantrone in patients affected by hepatocellular carcinoma with unfavorable prognostic factors. Oncology. 49(2):1992;139-142
50. Lai K.H., Tsai Y.T., Lee S.D., et al. Phase II study of mitoxantrone in unresectable primary hepatocellular carcinoma following hepatitis B infection. Cancer Chemother. Pharmacol. 23(1):1989;54-56
51. Falkson G., Lipsitz S., Borden E., Simson I., Haller D. Hepatocellular carcinoma: an ECOG randomized phase II study of beta- interferon and menagoril. Am. J. Clin. Oncol.: Cancer Clin. Trials. 18(4):1995;287-292
52. Tumolo S., Toffoli G., Bearz A., et al. Oral idarubicin for the treatment of hepatocellular carcinoma. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 2002;. [Abstract 635]
53. Tetef M., Doroshow J., Akman S., et al. 5-Fluorouracil and high-dose calcium leucovorin for hepatocellular carcinoma: a phase II trial. Cancer Invest. 13(5):1995;460-463
54. Link J.S., Bateman J.R., Paroly W.S., Durkin W.J., Peters R.L. 5-Flourouracil in hepatocellular carcinoma: report of twenty-one cases. Cancer. 39(5):1977;1936-1939
55. Porta C., Moroni M., Nastasi G., Arcangeli G. 5-Fluorouracil and d, l-leucovorin calcium are active to treat unresectable hepatocellular carcinoma patients: preliminary results of a phase II study. Oncology. 52(6):1995;487-491
56. Gebbia V., Maiello E., Serravezza G., et al. 5-Fluorouracil plus high dose levofolinic acid and oral hydroxyurea for the treatment of primary hepatocellular carcinomas: results of a phase II multicenter study of the Southern Italy Oncology Group (G.O.I.M). Anticancer Res. 19(2B):1999;1407-1410
57. Baker S.D., Diasio R.B., O'Reilly S., et al. Phase I and pharmacologic study of oral fluorouracil on a chronic daily schedule in combination with the dihydropyrimidine dehydrogenase inactivator eniluracil. J. Clin. Oncol. 18(4):2000;915-926
58. Benson A.B. III, Mitchell E., Abramson N., et al. Oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma. Ann. Oncol. 13(4):2002;576-581
59. Llovet J.M., Ruff P., Tassopoulos N., et al. A phase II trial of oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma. Eur. J. Cancer. 37(11):2001;1352-1358
60. Mani S., Schiano T., Garcia J.C., et al. Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced hepatocellular carcinoma. Invest. New Drugs. 16(3):1998;279-283
61. Ishikawa T., Ichida T., Sugitani S., et al. Improved survival with oral administration of enteric-coated tegafur/uracil for advanced stage IV-A hepatocellular carcinoma. J. Gastroenterol. Hepatol. 16(4):2001;452-459
62. Yamamoto M., Arii S., Sugahara K., Tobe T. Adjuvant oral chemotherapy to prevent recurrence after curative resection for hepatocellular carcinoma. Br. J. Surg. 83(3):1996;336-340
63. Lozano R.D., Patt Y.Z., Hassan M.M., et al. Oral capecitabine (Xeloda) for the treatment of hepatobiliary cancers (hepatocellular carcinoma, cholangiocarcinoma, and gallbladder cancer. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 2000;. [Abstract 1025]
64. Chun H.G., Waheed F., Iqbal D.C., Wolf Z., Li S., Kempin S.J. A combination of capecitabine and thalidomide in patients with unresectable, recurrent or metastatic hepatocellular carcinoma. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 2003;. [Abstract 1407]
65. Tanioka H., Tsuji A., Morita S., et al. Combination chemotherapy with continuous 5-fluorouracil and low-dose cisplatin infusion for advanced hepatocellular carcinoma. Anticancer Res. 23(2C):2003;1891-1897
66. Ellis P.A., Norman A., Hill A., et al. Epirubicin, cisplatin and infusional 5-fluorouracil (5-FU) (ECF) in hepatobiliary tumours. Eur. J. Cancer. 31A(10):1995;1594-1598
67. Boucher E., Corbinais S., Brissot P., Boudjema K., Raoul J.L. Treatment of hepatocellular carcinoma (HCC) with systemic chemotherapy combining epirubicin, cisplatinum and infusional 5-fluorouracil (ECF regimen). Cancer Chemother. Pharmacol. 50(4):2002;305-308
68. Leung T.W., Tang A.M., Zee B., et al. Factors predicting response and survival in 149 patients with unresectable hepatocellular carcinoma treated by combination cisplatin, interferon-alpha, doxorubicin and5-fluorouracil chemotherapy. Cancer. 94(2):2002;421-427
69. Kajanti M.J., Pyrhonen S.O. Phase II intravenous study of epirubicin with 5-fluorouracil in patients with advanced hepatocellular carcinoma. Eur. J. Cancer. 27(12):1991;1620-1622
70. Al-Idrissi H.Y., Ibrahim E.M., Abdel Satir A., Satti M.B., Al-Kasem S., Al-Qurain A. Primary hepatocellular carcinoma in the eastern province of Saudi Arabia: treatment with combination chemotherapy using 5-fluorouracil, Adriamycin and mitomycin-C. Hepatogastroenterology. 32(1):1985;8-10
71. Lin H.L., Liu T.Y., Chau G.Y., Lui W.Y., Chi C.W. Comparison of 2-methoxyestradiol-induced, docetaxel-induced, and paclitaxel-induced apoptosis in hepatoma cells and its correlation with reactive oxygen species. Cancer. 89(5):2000;983-994
72. Chao Y., Chan W.K., Birkhofer M.J., et al. Phase II and pharmacokinetic study of paclitaxel therapy for unresectable hepatocellular carcinoma patients. Br. J. Cancer. 78(1):1998;34-39
73. Strumberg D., Erhard J., Harstrick A., et al. Phase I study of a weekly 1 h infusion of paclitaxel in patients with unresectable hepatocellular carcinoma. Eur. J. Cancer. 34(8):1998;1290-1292
74. Matsuoka H., Yano K., Seo Y., et al. Cytotoxicity of CPT-11 for gastrointestinal cancer cells cultured on fixed-contact-sensitive plates. Anticancer Drugs. 6(3):1995;413-418
75. Chu X.Y., Kato Y., Ueda K., et al. Biliary excretion mechanism of CPT-11 and its metabolites in humans: involvement of primary active transporters. Cancer Res. 58(22):1998;5137-5143
76. O'Reilly E.M., Stuart K.E., Sanz-Altamira P.M., et al. A phase II study of irinotecan in patients with advanced hepatocellular carcinoma. Cancer. 91(1):2001;101-105
77. Boige V., Taieb J., Hebbar M., et al. A multicenter phase II study of irinotecan (CPT-11) in patients with advanced hepatocellular carcinoma. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 2002;. [Abstract 607]
78. Lee G.Y., Kim B.S., Seo Y.T., et al. Phase II study to topotecan and cisplatin in advanced hepatocellular carcinoma. Korean J. Intern. Med. 18(2):2003;104-108
79. Alexandre J., Tigaud J.M., Gross-Goupil M., et al. Combination of topotecan and oxaliplatin in inoperable hepatocellular cancer patients. Am. J. Clin. Oncol. 25(2):2002;198-203
80. Cavalli F., Rozencweig M., Renard J., Goldhirsch A., Hansen H.H. Phase II study of oral VP-16-213 in hepatocellular carcinoma. Eur. J. Cancer Clin. Oncol. 17(10):1981;1079-1082
81. Wierzbicki R., Ezzat A., Abdel-Warith A., et al. Phase II trial of chronic daily VP-16 administration in unresectable hepatocellular carcinoma (HCC. Ann. Oncol. 5(5):1994;466-467
82. Shiu W., Mok S.D., Leung N., et al. Phase 2 study of high dose etoposide (VP16-213) in hepatocellular carcinoma. Jpn. J. Clin. Oncol. 17(2):1987;113-115
83. Yoshino M., Okazaki N., Yoshida T., et al. A phase II study of etoposide in patients with hepatocellular carcinoma by the Tokyo Liver Cancer Chemotherapy Study Group. Jpn. J. Clin. Oncol. 19(2):1989;120-122
84. Cheng A.L., Chen Y.C., Yeh K.H., Chuang S.E., Chen B.R., Chen D.S. Chronic oral etoposide and tamoxifen in the treatment of far-advanced hepatocellular carcinoma. Cancer. 77(5):1996;872-877
85. ′ -difluorodeoxycytidine on human hepatoma HepG2 cells J. Hepatol. 28(3):1998;504-509
86. Yang T.S., Lin Y.C., Chen J.S., Wang H.M., Wang C.H. Phase II study of gemcitabine in patients with advanced hepatocellular carcinoma. Cancer. 89(4):2000;750-756
87. Ulrich-Pur H., Kornek G.V., Fiebiger W., Schull B., Raderer M., Scheithauer W. Treatment of advanced hepatocellular carcinoma with biweekly high-dose gemcitabine. Oncology. 60(4):2001;313-315
88. Kubicka S., Rudolph K.L., Tietze M.K., Lorenz M., Manns M. Phase II study of systemic gemcitabine chemotherapy for advanced unresectable hepatobiliary carcinomas. Hepatogastroenterology. 48(39):2001;783-789
89. Fuchs C.S., Clark J.W., Ryan D.P., et al. A phase II trial of gemcitabine in patients with advanced hepatocellular carcinoma. Cancer. 94(12):2002;3186-3191
90. Yang T.S., Chang W.C., Lin Y.C., Chen J.S., Liau C.T., Yeh K.Y. A phase II study of gemcitabine and cisplatin for patients with advanced hepatocellular carcinoma. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 2003;. [Abstract 1351]
91. Fuloria J., Parikh P., Prabhakaran P., et al. A multicentre, phase II trial of gemcitabine and cisplatin in unresectable hepatocellular carcinoma. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 2000;. [Abstract 1143]
92. Lozano R.D., Ellis L.M., Hassan M.M., Nooka A., Brown T.D., Patt Y.Z. Gemcitabine, amifostine and cisplatin, (GAP) for treatment of hepato-biliary cancer: a retrospective analysis in 50 patients. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 2003;. [Abstract 1498]
93. Okada S., Okazaki N., Nose H., Shimada Y., Yoshimori M., Aoki K. A phase 2 study of cisplatin in patients with hepatocellular carcinoma. Oncology. 50(1):1993;22-26
94. Stuart K., Tessitore J., Rudy J., Clendennin N., Johnston A. A Phase II trial of nolatrexed dihydrochloride in patients with advanced hepatocellular carcinoma. Cancer. 86(3):1999;410-414
95. Mok T.S., Leung T.W., Lee S.D., et al. A multi-centre randomized phase II study of nolatrexed versus doxorubicin in treatment of Chinese patients with advanced hepatocellular carcinoma. Cancer Chemother. Pharmacol. 44(4):1999;307-311
96. Hamburg S., Miller W., Garcia-Vargas J., Joseph J.L., Gundaker L.F., Horan J. Survival benefit of nolatrexed in advanced hepatocellular carcinoma. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 2003;. [Abstract 1157]
97. Stuart K., Eder J.P., Proper J., et al. Phase II trial of irofulven in patients with unresectable hepatocellular carcinoma (HCC). Proc. Annu. Meet. Am. Soc. Clin. Oncol. 2003;. [Abstract 1107]
98. Izzo F., Marra P., Beneduce G., et al. Phase I/II testing of pegylated arginine deaminase in subjects with hepatocellular carcinoma. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 2003;. [Abstract 1474]
99. Singh D.A., Kindler H.L., Eng C., et al. Phase II trial of the epothilone B analog BMS-247550 in patients with hepatobiliary cancer. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 22:2003;281. [Abstract 1127]
100. Reubi J.C., Laissue J.A. Multiple actions of somatostatin in neoplastic disease. Trends Pharmacol. Sci. 16(3):1995;110-115
101. Reubi J.C., Zimmermann A., Jonas S., et al. Regulatory peptide receptors in human hepatocellular carcinomas. Gut. 45(5):1999;766-774
102. Rabinowitz I., Telepak R., Lee F.C. Octreotide scans are positive in a subset of patients with hepatocellular carcinoma. Clin. Nuc. Med. 27(7):2002;499-502
103. Kouroumalis E., Skordilis P., Thermos K., Vasilaki A., Moschandrea J., Manousos O.N. Treatment of hepatocellular carcinoma with octreotide: a randomised controlled study. Gut. 42(3):1998;442-447
104. Dimitroulopoulos D., Xinopoulos D., Tsamakidis K., et al. The role of sandostatin LAR in treating patients with advanced hepatocellular cancer. Hepatogastroenterology. 49(47):2002;1245-1250
105. Samonakis D.N., Moschandreas J., Arnaoutis T., et al. Treatment of hepatocellular carcinoma with long acting somatostatin analogues. Oncol. Rep. 9(4):2002;903-907
106. Yuen M.F., Poon R.T., Lai C.L., et al. A randomized placebo-controlled study of long-acting octreotide for the treatment of advanced hepatocellular carcinoma. Hepatology. 36(3):2002;687-691
107. Rabe C., Pilz T., Allgaier H.P., et al. Clinical outcome of a cohort of 63 patients with hepatocellular carcinoma treated with octreotide. Z. Gastroenterol. 40(6):2002;395-400
108. Raderer M., Hejna M.H., Muller C., et al. Treatment of hepatocellular cancer with the long acting somatostatin analog lanreotide in vitro and in vivo. Int. J. Oncol. 16(6):2000;1197-1201
109. Villa E., Colantoni A., Grottola A., et al. Variant estrogen receptors and their role in liver disease. Mol. Cell Endocrinol. 193(1-2):2002;65-69
110. Chow P.K., Tai B.C., Tan C.K., et al. High-dose tamoxifen in the treatment of inoperable hepatocellular carcinoma: a multicenter randomized controlled trial. Hepatology. 36(5):2002;1221-1226
111. Chao Y., Chan W.K., Wang S.S., et al. Phase II study of megestrol acetate in the treatment of hepatocellular carcinoma. J. Gastroeterol. Hepatol. 12(4):1997;277-281
112. Colombo M., de Franchis R., Del Ninno E., et al. Hepatocellular carcinoma in Italian patients with cirrhosis. NEJM. 325(10):1991;675-680
113. Jonas S., Bechstein W.O., Heinze T., et al. Female sex hormone receptor status in advanced hepatocellular carcinoma and outcome after surgical resection. Surgery. 121(4):1997;456-461
114. Nagasue N., Kohno H., Chang Y., Hayashi T., Nakamura T. Specificity of androgen receptors of hepatocellular carcinoma and liver in humans. Hepatogastroenterology. 37(5):1990;474-479
115. Martinez Cerezo F.J., Tomas A., Donoso L., et al. Controlled trial of tamoxifen in patients with advanced hepatocellular carcinoma. J. Hepatol. 20(6):1994;702-706
116. Melia W.M., Johnson P.J., Williams R. Controlled clinical trial of doxorubicin and tamoxifen versus doxorubicin alone in hepatocellular carcinoma. Cancer Treat. Rep. 71(12):1987;1213-1216
117. Farinati F., De Maria N., Fornasiero A., et al. Prospective controlled trial with antiestrogen drug tamoxifen in patients with unresectable hepatocellular carcinoma. Dig. Dis. Sci. 37(5):1992;659-662
118. Farinati F., Salvagnini M., de Maria N., et al. Unresectable hepatocellular carcinoma: a prospective controlled trial with tamoxifen. J. Hepatol. 11(3):1990;297-301
119. Elba S., Giannuzzi V., Misciagna G., Manghisi O.G. Randomized controlled trial of tamoxifen versus placebo in inoperable hepatocellular carcinoma. Ital. J. Gastroenterol. 26(2):1994;66-68
120. Coll S., Sola R., Vila M., et al. Treatment with tamoxifen in patients with advanced hepatocellular carcinoma. Results of a randomized placebo controlled trial. Hepatology. 4(2):1995;404A
121. Castells A., Bruix J., Bru C., et al. Treatment of hepatocellular carcinoma with tamoxifen: a double-blind placebo-controlled trial in 120 patients. Gastroenterology. 109(3):1995;917-922
122. Liu C.L., Fan S.T., Ng I.O., Lo C.M., Poon R.T., Wong J. Treatment of advanced hepatocellular carcinoma with tamoxifen and the correlation with expression of hormone receptors: a prospective randomized study. Am. J. Gastroenterol. 95(1):2000;218-222
123. Barbare J-C, Milan C, Bouché O, et al. Treatment of advanced hepatocellular carcinoma (HCC) with tamoxifen: a phase III trial in 420 patients. In: Proc ASCO 21;2002 2002 [Abstract 551]
124. Riestra S., Rodriguez M., Delgado M., et al. Tamoxifen does not improve survival of patients with advanced hepatocellular carcinoma. J. Clin. Gastroenterol. 26(3):1998;200-203
125. Perrone F., Gallo C., Daniele B., et al. Tamoxifen in the treatment of hepatocellular carcinoma: 5-year results of the CLIP-1 multicentre randomised controlled trial. Curr. Pharm. Des. 8(11):2002;1013-1019
126. Colleoni M., Nelli P., Vicario G., Mastropasqua G., Manente P. Megestrol acetate in unresectable hepatocellular carcinoma. Tumori. 81(5):1995;351-353
127. Villa E., Ferretti I., Grottola A., et al. Hormonal therapy with megestrol in inoperable hepatocellular carcinoma characterized by variant oestrogen receptors. Br. J. Cancer. 84(7):2001;881-885
128. Mantovani G., Maccio A., Lai P., Massa E., Ghiani M., Santona M.C. Cytokine activity in cancer-related anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate. Semin. Oncol. 25(2 Suppl 6):1998;45-52
129. Negro F., Papotti M., Pacchioni D., Galimi F., Bonino F., Bussolati G. Detection of human androgen receptor mRNA in hepatocellular carcinoma by in situ hybridisation. Liver. 14(4):1994;213-219
130. Guy J.T., Auslander M.O. Androgenic steroids and hepatocellular carcinoma. Lancet. 1(7795):1973;148
131. Nagasue N., Yu L., Yamaguchi M., Kohno H., Tachibana M., Kubota H. Inhibition of growth and induction of TGF-beta 1 in human hepatocellular carcinoma with androgen receptor by cyproterone acetate in male nude mice. J. Hepatol. 25(4):1996;554-562
132. 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. 16(2):1998;411-417
133. Manesis E.K., Giannoulis G., Zoumboulis P., Vafiadou I., Hadziyannis S.J. Treatment of hepatocellular carcinoma with combined suppression and inhibition of sex hormones: a randomized, controlled trial. Hepatology. 21(6):1995;1535-1542
134. Chao Y., Chan W.K., Huang Y.S., et al. Phase II study of flutamide in the treatment of hepatocellular carcinoma. Cancer. 77(4):1996;635-639
135. Forbes A., Wilkinson M.L., Iqbal M.J., Johnson P.J., Williams R. Response to cyproterone acetate treatment in primary hepatocellular carcinoma is related to fall in free 5 alpha-dihydrotestosterone. Eur. J. Cancer Clin. Oncol. 23(11):1987;1659-1664
136. Grosh W, Mueller S, Alexander BF, Caldwell S, Cohen R. Anastrozole (A) treament of patients IPTS) with advanced unresectable hepatocellular carcinoma (HCC). Proc Annu Meet Am Soc Clin Oncol [Abstract 1096]
137. Radaeva S., Jaruga B., Hong F., et al. Interferon-alpha activates multiple STAT signals and down-regulates c-Met in primary human hepatocytes. Gastroenterology. 122(4):2002;1020-1034
138. Sachs E., Di Bisceglie A.M., Dusheiko G.M., et al. Treatment of hepatocellular carcinoma with recombinant leucocyte interferon: a pilot study. Br. J. Cancer. 52(1):1985;105-109
139. The Gastrointestinal Tumor Study Group. A prospective trial of recombinant human interferon alpha2B in previously untreated patients with hepatocellular carcinoma. Cancer 1990;66(1):135-9
140. Yoshida T., Okazaki N., Yoshino M., Okhura H., Shimada Y. Phase II trial of high dose recombinant gamma-interferon in advanced hepatocellular carcinoma. Eur. J. Cancer. 26(4):1990;545-546
141. Lai C.L., Wu P.C., Lok A.S., et al. Recombinant alpha 2 interferon is superior to doxorubicin for inoperable hepatocellular carcinoma: a prospective randomised trial. Br. J. Cancer. 60(6):1989;928-933
142. Lai C.L., Lau J.Y., Wu P.C., et al. Recombinant interferon-alpha in inoperable hepatocellular carcinoma: a randomized controlled trial. Hepatology. 17(3):1993;389-394
143. Llovet J.M., Sala M., Castells L., et al. Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma. Hepatology. 31(1):2000;54-58
144. Kubo S., Nishiguchi S., Hirohashi K., et al. Effects of long-term postoperative interferon-alpha therapy on intrahepatic recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. A randomized, controlled trial. Ann. Int. Med. 134(10):2001;963-967
145. Ikeda K., Arase Y., Saitoh S., et al. Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor-A prospective randomized study of hepatitis C virus-related liver cancer. Hepatology. 32(2):2000;228-232
146. Feun L.G., Savaraj N., Hung S., et al. A phase II trial of recombinant leukocyte interferon plus doxorubicin in patients with hepatocellular carcinoma. Am. J. Clin. Oncol. 17(5):1994;393-395
147. Kardinal C.G., Moertel C.G., Wieand H.S., et al. Combined doxorubicin and alpha-interferon therapy of advanced hepatocellular carcinoma. Cancer. 71(7):1993;2187-2190
148. Bokemeyer C., Kynast B., Harstrick A., et al. No synergistic activity of epirubicin and interferon-alpha 2b in the treatment of hepatocellular carcinoma. Cancer Chemother. Pharmacol. 35(4):1995;334-338
149. Lotz J.P., Grange J.D., Hannoun L., et al. Treatment of unresectable hepatocellular carcinoma with a combination of human recombinant alpha-2b interferon and doxorubicin: results of a pilot study. Eur. J. Cancer. 30A(9):1994;1319-1325
150. Kountouras J., Boura P., Karolides A., Zaharioudaki E., Tsapas G. Recombinant a2 interferon (a-IFN) with chemo-hormonal therapy in patients with hepatocellular carcinoma (HCC. Hepatogastroenterology. 42(1):1995;31-36
151. Brook M.G., Dunk A.A., McDonald J.A., Lever A.M., Goh C., Thomas H.C. Human lymphoblastoid interferon does not increase survival when added to mitozantrone in the treatment of hepatocellular carcinomas. Aliment. Pharmacol. Ther. 1(4):1987;315-320
152. Colleoni M., Buzzoni R., Bajetta E., et al. A phase II study of mitoxantrone combined with beta-interferon in unresectable hepatocellular carcinoma. Cancer. 72(11):1993;3196-3201
153. Komorizono Y., Kohara K., Oketani M., et al. Systemic combined chemotherapy with low dose of 5-fluorouracil, cisplatin, and interferon-alpha for advanced hepatocellular carcinoma: a pilot study. Dig. Dis. Sci. 48(5):2003;877-881
154. Feun L.G., O'Brien C., Molina E., et al. Recombinant leukocyte interferon, doxorubicin, and 5-FUDR in patients with hepatocellular carcinoma-A phase II trial. J. Cancer Res. Clin. Oncol. 129(1):2003;17-20
155. Stuart K., Tessitore J., Huberman M. 5-Fluorouracil and alpha-interferon in hepatocellular carcinoma. Am. J. Clin. Oncol. 19(2):1996;136-139
156. Ji S.K., Park N.H., Choi H.M., et al. Combined cis-platinum and alpha interferon therapy of advanced hepatocellular carcinoma. Korean J. Intern. Med. 11(1):1996;58-68
157. Kaneko S., Urabe T., Kobayashi K. Combination chemotherapy for advanced hepatocellular carcinoma complicated by major portal vein thrombosis. Oncology. 62(Suppl 1):2002;69-73
158. Patt Y.Z., Hassan M.M., Lozano R.D., et al. Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma. J. Clin. Oncol. 21(3):2003;421-427
159. Iwashita Y., Tahara K., Goto S., et al. A phase I study of autologous dendritic cell-based immunotherapy for patients with unresectable primary liver cancer. Cancer Immunol. Immunother. 52(3):2003;155-161
160. Haruta I., Yamauchi K., Aruga A., et al. Analytical study of the clinical response to two distinct adoptive immunotherapies for advanced hepatocellular carcinoma: comparison between LAK cell and CTL therapy. J. Immunother. Emphasis Tumor Immunol. 19(3):1996;218-223
161. Reinisch W., Holub M., Katz A., et al. Prospective pilot study of recombinant granulocyte-macrophage colony-stimulating factor and interferon-gamma in patients with inoperable hepatocellular carcinoma. J. Immunother. 25(6):2002;489-499
162. Aldeghi R., Lissoni P., Barni S., et al. Low-dose interleukin-2 subcutaneous immunotherapy in association with the pineal hormone melatonin as a first-line therapy in locally advanced or metastatic hepatocellular carcinoma. Eur. J. Cancer. 30A(2):1994;167-170
163. Meyskens F.L. Jr., Jacobson J., Nguyen B., Weiss G.R., Gandara D.R., MacDonald J.S. Phase II trial of oral beta-all trans-retinoic acid in hepatocellular carcinoma (SWOG 9157). Invest. New Drugs. 16(2):1998;171-173
164. Feun L.G., Marini A., Molina E., et al. Thalidomide as palliative care for patients with unresectable hepatocellular carcinoma. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 22:2003;. [Abstract 865]
165. Lin A, Brophy N, Fisher GA, et al. Phase II study of thalidomide in patients with unresectable hepatocellular carcinoma. Proc Annu Meet Am Soc Clin Oncol [Abstract 2202]
166. Kong HL, Boyer MJ, Lim R, Clarke S, Millward MJ, Wong JEL. Phase II trial of thalidomide in unresectable hepatocellular carcinoma: a Cancer Therapeutics Research Group study. Proc Annu Meet Am Soc Clin Oncol [Abstract 2282]
167. Patt YZ, Hassan MM, Lozano RD, et al. Phase II trial of Thalidomid for treatment of non-resectable hepatocellular carcinoma. Proc Annu Meet Am Soc Clin Oncol [Abstract 1035]
168. Chen C.-.S., Hillebrand D., Hill K., Lilly M. A pilot study of celecoxib combined with escalating doses of thalidomide for treatment of unresectable hepatocellular carcinoma. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 2002;. [Abstract 2350]
169. Treiber G., Heinrich U., Fostitch P., Roecken C., Malfertheiner P. Palliative treatment of hepatocellular carcinoma (HCC) using octreotide, rofecoxib, or both. Proc. Annu. Meet. Am. Soc. Clin. Oncol. 22:2003;319. [Abstract 1281]
170. Burris H., Storniolo A.M. Assessing clinical benefit in the treatment of pancreas cancer: gemcitabine compared to 5-fluorouracil. Eur. J. Cancer. 33(Suppl 1):1997;S18-S22
171. Kane M.A., Brooks A. New immunization initiatives and progress toward the global control of hepatitis B. Curr. Opin. Inf. Dis. 15(5):2002;465-469
172. Lin H.H., Wang L.Y., Hu C.T., et al. Decline of hepatitis B carrier rate in vaccinated and unvaccinated subjects: sixteen years after newborn vaccination program in Taiwan. J. Med. Virol. 69(4):2003;471-474
173. Koff R.S. Hepatitis vaccines: recent advances. Int. J. Parasitol. 33(5-6):2003;517-523
174. Wun Y.T., Dickinson J.A. Alpha-fetoprotein and/or liver ultrasonography for liver cancer screening in patients with chronic hepatitis B. Cochrane Database Syst. Rev. 3:2003;3