Summary
The approval of sorafenib as the first effective drug for the treatment of advanced hepatocellular carcinoma (HCC) represents a milestone in the treatment of this disease. Likewise, the combination of cisplatin and gemcitabine was adopted as a first-line standard chemotherapy option for the treatment of advanced biliary tract cancers based on the results from a large randomized study (ABC-02). This review will briefly summarize the rationale, status and future perspectives of innovative targeted approaches for the treatment of hepatocellular and biliary tract carcinomas. Data from ongoing trials will likely result in a further refinement of treatment recommendations over the course of the next few years.
Similar content being viewed by others
References
Zhu AX. Systemic therapy of advanced hepatocellular carcinoma: how hopeful should we be? Oncologist, 11: 790–800, 2006
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 359: 378–390, 2008
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, 10(1): 25–34, 2009
Hopfner M, Schuppan D, Scherubl H. Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer. World J Gastroenterol, 14: 1–14, 2008
Llovet JM, Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology, 48: 1312–1327, 2008
Khan SA, Davidson BR, Goldin R, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document. Gut, 51 (Suppl 6): VI1–VI9, 2002
Burris HA 3rd, Moore MJ, Andersen J et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol, 15(6): 2403–2413, 1997
Eckel F, Schmid RM. Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer, 96(6): 896–902, 2007. Epub Feb 27, 2007
Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med, 362(14): 1273–1281, 2010
Jarnagin WR, Schwartz LH, Gultekin DH et al. Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival. Ann Oncol. 20(9): 1589–1595, 2009. Epub 2009 Jun 2
Rea DJ, Heimbach JK, Rosen CB, et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg; 242(3): 451–458, 2005. discussion 458–461
Schwartz JJ, Hutson WR, Gayowski TJ, et al. Liver transplantation for cholangiocarcinoma. Transplantation, 88(3): 295–298, 2009
Riener MO, Stenner F, Liewen H, et al. Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas. Hepatology, 49(5): 1602–1609, 2009
Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol, 24: 25–35, 2006
Zhu AX, Dushyant vs. Duda DG, et al. Efficacy, safety, and potencial biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol, 27: 3027–3035, 2009
Koeberle D, Montemurro M, Samaras P, et al. Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06). Oncologist, 15(3): 285–292, 2010
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, 20: 26(18): 2992–2998, 2008
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, 20: 27(6): 843–850, 2009
Hsu CH, Yang TS, Hsu C, Toh HC, et al. Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced hepatocellular carcinoma. Br J Cancer, 102(6): 981–986, 2010
Philip PA, Mahoney MR, Allmer C, et al. Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer. J Clin Oncol, 23(27): 6657–6663, 2005
Blaszkowsky LS, Abrams TA, Miksad RA, et al. Phase I/II study of everolimus in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol, 28 (suppl; abstr e14542), 2010
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). J Clin Oncol, 27: 15s, 2009 (suppl; abstr 4577)
Toh H, Chen P, Carr BI, et al. Linifanib phase II trial in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol, 28:15s, 2010 (suppl; abstr 4038)
Philip PA, Mahoney MR, Allmer C, et al. Phase II study of erlotinib in patients with advanced biliary cancer. J Clin Oncol, 24(19): 3069–3074, 2006
Ramanathan RK, Belani CP, Singh DA, et al. A phase II study of lapatinib in patients with advanced biliary tree and hepatocellular cancer. Cancer Chemother Pharmacol, 64(4): 777–783, 2009. Epub 2009 Jan 24
Bengala C, Bertolini F, Malavasi N, et al. Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial. Br J Cancer, 102(1): 68–72, 2010. Epub 2009 Nov 24
Zhu AX, Meyerhardt JA, Blaszkowsky LS, et al. Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol, 11(1): 48–54, 2010. Epub 2009 Nov 20
Lubner SJ, Mahoney MR, Kolesar JL, et al. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II Consortium study. J Clin Oncol, 28(21): 3491–3497, 2010. Epub 2010 Jun 7
Grünberger B, Schueller J, Heubrandtner U, et al. Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study. Lancet Oncol, 11(12): 1142–1148, 2010. Epub 2010 Nov 9
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Koeberle, D., Samaras, P. Recent advances and future challenges in the treatment of hepatocellular and biliary tract carcinomas. memo 4, 94–97 (2011). https://doi.org/10.1007/s12254-011-0260-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12254-011-0260-9