Are there opportunities for chemotherapy in the treatment of hepatocellular cancer?

Journal of Hepatology

Volumn 56, Issue 3, 2012, Pages 686-695

  Asghar, Uzma ^a   Meyer, Tim ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Chemotherapy; Doxorubicin; Hepatocellular; Hypoxia; mTOR; Resistance; Sorafenib

Indexed keywords

AFLATOXIN B1; BATABULIN; BEVACIZUMAB; CETUXIMAB; CISPLATIN; CYCLOPHOSPHAMIDE; DACARBAZINE; DOXORUBICIN; EVEROLIMUS; EXCISION REPAIR CROSS COMPLEMENTING PROTEIN 1; FLUOROURACIL; GEMCITABINE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INTERFERON; IRINOTECAN; MAMMALIAN TARGET OF RAPAMYCIN; METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; MONOCLONAL ANTIBODY DC101; NOLATREXED; OXALIPLATIN; PANITUMUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; RAPAMYCIN; SORAFENIB; STREPTOZOCIN; TEMOZOLOMIDE; TEMSIROLIMUS; UFT; UNINDEXED DRUG; VASCULOTROPIN RECEPTOR 2;

APOPTOSIS; BREAST CANCER; CANCER CHEMOTHERAPY; CELL CYCLE ARREST; CHEMOEMBOLIZATION; CLINICAL TRIAL (TOPIC); COLON CANCER; COLORECTAL CANCER; DIARRHEA; DNA REPAIR; DOUBLE BLIND PROCEDURE; DRUG WITHDRAWAL; FATIGUE; FOLLOW UP; GLIOBLASTOMA; HUMAN; HYPERTENSION; LIVER CELL CARCINOMA; LOW DRUG DOSE; MORTALITY; NONHODGKIN LYMPHOMA; OVARY CANCER; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; SKIN MANIFESTATION; SURVIVAL RATE; SYSTOLIC DYSFUNCTION;

ANTIBIOTICS, ANTINEOPLASTIC; BENZENESULFONATES; CARCINOMA, HEPATOCELLULAR; DOXORUBICIN; HUMANS; LIVER NEOPLASMS; PYRIDINES;

EID: 84857358680     PISSN: 01688278     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jhep.2011.07.031     Document Type: Review

References (73)

1. J.M. Llovet, A. Burroughs, and J. Bruix Hepatocellular carcinoma Lancet 362 2003 1907 1917
2. J.M. Llovet, and J. Bruix Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival Hepatology 37 2003 429 442
3. J.M. Llovet, A.M. Di Bisceglie, J. Bruix, B.S. Kramer, R. Lencioni, and A.X. Zhu Design and endpoints of clinical trials in hepatocellular carcinoma J Natl Cancer Inst 100 2008 698 711
4. J.M. Llovet, J. Bustamante, A. Castells, R. Vilana, M.C. Ayuso, and M. Sala Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials Hepatology 29 1999 62 67
5. J.M. Llovet, S. Ricci, V. Mazzaferro, P. Hilgard, E. Gane, and J.F. Blanc Sorafenib in advanced hepatocellular carcinoma N Engl J Med 359 2008 378 390
6. J.C. Barbare, O. Bouche, F. Bonnetain, J.L. Raoul, P. Rougier, and A. Abergel Randomized controlled trial of tamoxifen in advanced hepatocellular carcinoma J Clin Oncol 23 2005 4338 4346
7. A.L. Cheng, Y.K. Kang, Z. Chen, C.J. Tsao, S. Qin, and J.S. Kim 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 10 2009 25 34
8. A. Burroughs, D. Hochhauser, and T. Meyer Systemic treatment and liver transplantation for hepatocellular carcinoma: two ends of the therapeutic spectrum Lancet Oncol 5 2004 409 418
9. C.L. Olweny, T. Toya, E. Katongole-Mbidde, J. Mugerwa, S.K. Kyalwazi, and H. Cohen Treatment of hepatocellular carcinoma with adriamycin. Preliminary communication Cancer 36 1975 1250 1257
10. R.G. Simonetti, A. Liberati, C. Angiolini, and L. Pagliaro Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials Ann Oncol 8 1997 117 136
11. T.W. Leung, Y.Z. Patt, W.Y. Lau, S.K. Ho, S.C. Yu, and A.T. Chan Complete pathological remission is possible with systemic combination chemotherapy for inoperable hepatocellular carcinoma Clin Cancer Res 5 1999 1676 1681
12. C.L. Lai, P.C. Wu, G.C. Chan, A.S. Lok, and H.J. Lin Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial Cancer 62 1988 479 483
13. W. Yeo, T.S. Mok, B. Zee, T.W. Leung, P.B. Lai, and W.Y. Lau 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 97 2005 1532 1538
14. T. Ishikawa, T. Ichida, S. Sugitani, Y. Tsuboi, T. Genda, and S. Sugahara Improved survival with oral administration of enteric-coated tegafur/uracil for advanced stage IV-A hepatocellular carcinoma J Gastroenterol Hepatol 16 2001 452 459
15. J. Posey, P. Johnson, T. Mok, M. Hirmand, S. Dahlberg, and L. Kwei Results of a phase 2/3 open-label, randomized trial of T138067 versus doxorubicin (DOX) in chemotherapy-naïve, unresectable hepatocellular carcinoma (HCC) J Clin Oncol 23 2005
16. R.G. Gish, C. Porta, L. Lazar, P. Ruff, R. Feld, and A. Croitoru Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin J Clin Oncol 25 2007 3069 3075
17. S. Qin, Y. Bai, S. Ye, J. Fan, H. Lim, and J.Y. Cho Phase III study of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) versus doxorubicin as palliative systemic chemotherapy in advanced HCC in Asian patients J Clin Oncol 28 2010
18. J.M. Llovet, C. Bru, and J. Bruix Prognosis of hepatocellular carcinoma: the BCLC staging classification Semin Liver Dis 19 1999 329 338
19. G. Cabibbo, M. Enea, M. Attanasio, J. Bruix, A. Craxi, and C. Camma A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma Hepatology 51 2010 1274 1283
20. J.M. Llovet, and J. Bruix Molecular targeted therapies in hepatocellular carcinoma Hepatology 48 2008 1312 1327
21. H. Richly, B.F. Henning, P. Kupsch, K. Passarge, M. Grubert, and R.A. Hilger Results of a Phase I trial of sorafenib (BAY 43-9006) in combination with doxorubicin in patients with refractory solid tumors Ann Oncol 17 2006 866 873
22. H. Richly, B. Schultheis, I.A. Adamietz, P. Kupsch, M. Grubert, and R.A. Hilger Combination of sorafenib and doxorubicin in patients with advanced hepatocellular carcinoma: results from a phase I extension trial Eur J Cancer 45 2009 579 587
23. G.K. Abou-Alfa, P. Johnson, J.J. Knox, M. Capanu, I. Davidenko, and J. Lacava Doxorubicin plus sorafenib vs. doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial JAMA 304 2010 2154 2160
24. K.D. Miller, L.I. Chap, F.A. Holmes, M.A. Cobleigh, P.K. Marcom, and L. Fehrenbacher Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer J Clin Oncol 23 2005 792 799
25. B.J. Giantonio, P.J. Catalano, N.J. Meropol, P.J. O'Dwyer, E.P. Mitchell, and S.R. Alberts Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200 J Clin Oncol 25 2007 1539 1544
26. L.B. Saltz, S. Clarke, E. Diaz-Rubio, W. Scheithauer, A. Figer, and R. Wong Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study J Clin Oncol 26 2008 2013 2019
27. H. Hurwitz, L. Fehrenbacher, W. Novotny, T. Cartwright, J. Hainsworth, and W. Heim Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer N Engl J Med 350 2004 2335 2342
28. A.X. Zhu, L.S. Blaszkowsky, D.P. Ryan, J.W. Clark, A. Muzikansky, and K. Horgan Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma J Clin Oncol 24 2006 1898 1903
29. W. Sun, D. Sohal, D.G. Haller, K. Mykulowycz, M. Rosen, and M.C. Soulen Phase 2 trial of bevacizumab, capecitabine, and oxaliplatin in treatment of advanced hepatocellular carcinoma Cancer 2011
30. C.H. Hsu, T.S. Yang, C. Hsu, H.C. Toh, R.J. Epstein, and L.T. Hsiao Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced hepatocellular carcinoma Br J Cancer 102 2010 981 986
31. V. Boige, J.L. Raoul, J.P. Pignon, O. Bouche, J.F. Blanc, and L. Dahan Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial Br J Cancer 97 2007 862 867
32. S. Louafi, V. Boige, M. Ducreux, L. Bonyhay, T. Mansourbakht, and B.T. de Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC): results of a phase II study Cancer 109 2007 1384 1390
33. A.B. Siegel, E.I. Cohen, A. Ocean, D. Lehrer, A. Goldenberg, and J.J. Knox Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma J Clin Oncol 26 2008 2992 2998
34. C.E. Van, C.H. Kohne, E. Hitre, J. Zaluski, C.R. Chang Chien, and A. Makhson Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer N Engl J Med 360 2009 1408 1417
35. J.Y. Douillard, S. Siena, J. Cassidy, J. Tabernero, R. Burkes, and M. Barugel Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study J Clin Oncol 28 2010 4697 4705
36. A. Asnacios, L. Fartoux, O. Romano, C. Tesmoingt, S.S. Louafi, and T. Mansoubakht Gemcitabine plus oxaliplatin (GEMOX) combined with cetuximab in patients with progressive advanced stage hepatocellular carcinoma: results of a multicenter phase 2 study Cancer 112 2008 2733 2739
37. M.A. Buendia Genetics of hepatocellular carcinoma Semin Cancer Biol 10 2000 185 200
38. H.G. Woo, X.W. Wang, A. Budhu, Y.H. Kim, S.M. Kwon, and Z.Y. Tang Association of TP53 mutations with stem cell-like gene expression and survival of patients with hepatocellular carcinoma Gastroenterology 140 2011 1063 1070
39. B. Bressac, M. Kew, J. Wands, and M. Ozturk Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa Nature 350 1991 429 431
40. S.P. Hussain, J. Schwank, F. Staib, X.W. Wang, and C.C. Harris TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer Oncogene 26 2007 2166 2176
41. S.D. Zabludoff, C. Deng, M.R. Grondine, A.M. Sheehy, S. Ashwell, and B.L. Caleb AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies Mol Cancer Ther 7 2008 2955 2966
42. H. Hirai, Y. Iwasawa, M. Okada, T. Arai, T. Nishibata, and M. Kobayashi Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents Mol Cancer Ther 8 2009 2992 3000
43. X.Q. Wang, W.M. Ongkeko, L. Chen, Z.F. Yang, P. Lu, and K.K. Chen Octamer 4 (Oct4) mediates chemotherapeutic drug resistance in liver cancer cells through a potential Oct4-AKT-ATP-binding cassette G2 pathway Hepatology 52 2010 528 539
44. S. Ma, T.K. Lee, B.J. Zheng, K.W. Chan, and X.Y. Guan CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway Oncogene 27 12 2008 1749 1758
45. I. Beuvink, A. Boulay, S. Fumagalli, F. Zilbermann, S. Ruetz, and T. O'Reilly The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation Cell 120 2005 747 759
46. K.H. Tam, Z.F. Yang, C.K. Lau, C.T. Lam, R.W. Pang, and R.T. Poon Inhibition of mTOR enhances chemosensitivity in hepatocellular carcinoma Cancer Lett 273 2009 201 209
47. A.C. Piguet, D. Semela, A. Keogh, L. Wilkens, D. Stroka, and C. Stoupis Inhibition of mTOR in combination with doxorubicin in an experimental model of hepatocellular carcinoma J Hepatol 49 2008 78 87
48. F. Fornari, M. Milazzo, P. Chieco, M. Negrini, G.A. Calin, and G.L. Grazi MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells Cancer Res 70 2010 5184 5193
49. C.K. Lau, Z.F. Yang, D.W. Ho, M.N. Ng, G.C. Yeoh, and R.T. Poon An Akt/hypoxia-inducible factor-1alpha/platelet-derived growth factor-BB autocrine loop mediates hypoxia-induced chemoresistance in liver cancer cells and tumorigenic hepatic progenitor cells Clin Cancer Res 15 2009 3462 3471
50. T. Browder, C.E. Butterfield, B.M. Kraling, B. Shi, B. Marshall, and M.S. O'Reilly Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer Cancer Res 60 2000 1878 1886
51. G. Klement, P. Huang, B. Mayer, S.K. Green, S. Man, and P. Bohlen Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts Clin Cancer Res 8 2002 221 232
52. G. Klement, S. Baruchel, J. Rak, S. Man, K. Clark, and D.J. Hicklin Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity J Clin Invest 105 2000 R15 R24
53. R.S. Kerbel Improving conventional or low dose metronomic chemotherapy with targeted antiangiogenic drugs Cancer Res Treat 39 2007 150 159
54. E. Pasquier, M. Kavallaris, and N. Andre Metronomic chemotherapy: new rationale for new directions Nat Rev Clin Oncol 7 2010 455 465
55. M. Colleoni, L. Orlando, G. Sanna, A. Rocca, P. Maisonneuve, and G. Peruzzotti Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects Ann Oncol 17 2006 232 238
56. A. Bottini, D. Generali, M.P. Brizzi, S.B. Fox, A. Bersiga, and S. Bonardi Randomized phase II trial of letrozole and letrozole plus low-dose metronomic oral cyclophosphamide as primary systemic treatment in elderly breast cancer patients J Clin Oncol 24 2006 3623 3628
57. A. Sanchez-Munoz, C. Mendiola, E. Perez-Ruiz, C.A. Rodriguez-Sanchez, J.M. Jurado, and L. Alonso-Carrion Bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer Oncology 79 2010 98 104
58. D.S. Kong, J.I. Lee, J.H. Kim, S.T. Kim, W.S. Kim, and Y.L. Suh Phase II trial of low-dose continuous (metronomic) treatment of temozolomide for recurrent glioblastoma Neuro Oncol 12 2010 289 296
59. R. Buckstein, R.S. Kerbel, Y. Shaked, R. Nayar, C. Foden, and R. Turner High-Dose celecoxib and metronomic "low-dose" cyclophosphamide is an effective and safe therapy in patients with relapsed and refractory aggressive histology non-Hodgkin's lymphoma Clin Cancer Res 12 2006 5190 5198
60. T.C. Tang, S. Man, C.R. Lee, P. Xu, and R.S. Kerbel Impact of metronomic UFT/cyclophosphamide chemotherapy and antiangiogenic drug assessed in a new preclinical model of locally advanced orthotopic hepatocellular carcinoma Neoplasia 12 2010 264 274
61. T.C. Tang, S. Man, P. Xu, G. Francia, K. Hashimoto, and U. Emmenegger Development of a resistance-like phenotype to sorafenib by human hepatocellular carcinoma cells is reversible and can be delayed by metronomic UFT chemotherapy Neoplasia 12 2010 928 940
62. C.H. Hsu, Y.C. Shen, Z.Z. Lin, P.J. Chen, Y.Y. Shao, and Y.H. Ding Phase II study of combining sorafenib with metronomic tegafur/uracil for advanced hepatocellular carcinoma J Hepatol 53 2010 126 131
63. A.A. Brandes, A. Tosoni, G. Cavallo, M. Reni, E. Franceschi, and L. Bonaldi Correlations between O6-methylguanine DNA methyltransferase promoter methylation status, 1p and 19q deletions, and response to temozolomide in anaplastic and recurrent oligodendroglioma: a prospective GICNO study J Clin Oncol 24 2006 4746 4753
64. M.E. Hegi, A.C. Diserens, T. Gorlia, M.F. Hamou, T.N. de, and M. Weller MGMT gene silencing and benefit from temozolomide in glioblastoma N Engl J Med 352 2005 997 1003
65. Y.J. Zhang, Y. Chen, H. Ahsan, R.M. Lunn, P.H. Lee, and C.J. Chen Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation and its relationship to aflatoxin B1-DNA adducts and p53 mutation in hepatocellular carcinoma Int J Cancer 103 2003 440 444
66. E.J. Formeister, M. Tsuchiya, H. Fujii, S. Shpyleva, I.P. Pogribny, and I. Rusyn Comparative analysis of promoter methylation and gene expression endpoints between tumorous and non-tumorous tissues from HCV-positive patients with hepatocellular carcinoma Mutat Res 692 2010 26 33
67. S. Nomoto, T. Kinoshita, K. Kato, S. Otani, H. Kasuya, and S. Takeda Hypermethylation of multiple genes as clonal markers in multicentric hepatocellular carcinoma Br J Cancer 97 2007 1260 1265
68. S. Ueda, K. Shirabe, K. Morita, K. Umeda, H. Kayashima, and H. Uchiyama Evaluation of ERCC1 expression for cisplatin sensitivity in human hepatocellular carcinoma Ann Surg Oncol 2010
69. A. Fautrel, L. Andrieux, O. Musso, K. Boudjema, A. Guillouzo, and S. Langouet Overexpression of the two nucleotide excision repair genes ERCC1 and XPC in human hepatocellular carcinoma J Hepatol 43 2005 288 293
70. L.O. Andrieux, A. Fautrel, A. Bessard, A. Guillouzo, G. Baffet, and S. Langouet GATA-1 is essential in EGF-mediated induction of nucleotide excision repair activity and ERCC1 expression through ERK2 in human hepatoma cells Cancer Res 67 2007 2114 2123
71. B.K. Yoo, L. Emdad, Z.Z. Su, A. Villanueva, D.Y. Chiang, and N.D. Mukhopadhyay Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression J Clin Invest 119 2009 465 477
72. B.K. Yoo, R. Gredler, N. Vozhilla, Z.Z. Su, D. Chen, and T. Forcier Identification of genes conferring resistance to 5-fluorouracil Proc Natl Acad Sci USA 106 2009 12938 12943
73. B.K. Yoo, D. Chen, Z.Z. Su, R. Gredler, J. Yoo, and K. Shah Molecular mechanism of chemoresistance by astrocyte elevated gene-1 Cancer Res 70 2010 3249 3258