Therapie des hepatozellulären Karzinoms

Zusammenfassung

Das hepatozelluläre Karzinom (HCC) ist weltweit einer der häufigsten malignen Tumoren mit steigender Inzidenz auch in westlichen Ländern. Das HCC wird typischerweise erst relativ spät im Verlauf diagnostiziert und bis auf wenige Ausnahmen ist die Prognose ungünstig. Potenziell kurative Therapieansätze sind die Tumorresektion und in ausgewählten Fällen die Lebertransplantation. Diese chirurgischen Verfahren kommen aber aufgrund des Tumorstadiums oder der Leberfunktion für einen Großteil der Patienten nicht infrage. Weitere nichtchirurgische Therapieverfahren wie Radiofrequenzthermo- und Kryoablation, Alkohol- oder Säureinjektionen, transarterielle Chemoembolisationen, Strahlentherapie und systemische Chemotherapie können einzeln oder in Kombination in den verschiedenen Stadien der Erkrankung eingesetzt werden, um eine Verlängerung des (rezidivfreien) Überlebens und in wenigen Fällen auch eine Heilung zu erzielen.

Abstract

Hepatocellular carcinoma is one of the most common cancers worldwide. The incidence of this disease is also increasing in the Western world. Typically, HCC is diagnosed when patients have already reached an advanced stage of the disease and the prognosis is poor. Potentially curative treatment options include surgical resection or liver transplantation and can be offered to patients with adequate liver function and tumour stage. Other non-surgical treatment options such as radiofrequency ablation, cryoablation, ethanol or acetic acid injection, transarteriel chemoembolisation radiation therapy and systemic chemotherapy can be offered either alone or in combination to selected groups of patients. These treatments can improve (tumour-free) survival and in a few cases even cure the patient.

Schlüsselwörter

Leber - Chemotherapie - Krebs

Key words

Liver - chemotherapy - cancer

Reference

• 1 Parkin D M, Bray F, Ferlay J. et al . Estimating the world cancer burden: Globocan 2000.  Int J Cancer. 2001;  44 153-156
• 2 Deuffic S, Poynard T, Buffat L. et al . Trends in primary liver cancer.  Lancet. 1998;  44 214-215
• 3 El-Serag H B, Mason A C. Rising incidence of hepatocellular carcinoma in the United States.  N Engl J Med. 1999;  44 745-750
• 4 Fattovich G, Giustina G, Degos F. et al . Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients.  Gastroenterology. 1997;  44 463-472
• 5 Talwalkar J A, Gores G J. Diagnosis and staging of hepatocellular carcinoma.  Gastroenterology. 2004;  44 S126-S132
• 6 Marrero J A, Fontana R J, Barrat A. et al . Prognosis of hepatocellular carcinoma: Comparison of 7 staging systems in an American cohort.  Hepatology. 2005;  44 707-715
• 7 Okuda K, Ohtsuki T, Obata H. et al . Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients.  Cancer. 1985;  44 918-928
• 8 Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. The Cancer of the Liver Italian Program (CLIP) Investigators.  Hepatology. 2000;  44 840-845
• 9 Llovet J M, Fuster J, Bruix J. The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma.  Liver Transpl. 2004;  44 S115-S120
• 10 Kudo M, Chung H, Haji S. et al . Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score.  Hepatology. 2004;  44 1396-1405
• 11 Mazzaferro V, Regalia E, Doci R. et al . Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.  N Engl J Med. 1996;  44 693-699
• 12 Villa E, Colantoni A, Camma C. et al . Estrogen receptor classification for hepatocellular carcinoma: comparison with clinical staging systems.  J Clin Oncol. 2003;  44 441-446
• 13 Schwartz M. Liver transplantation for hepatocellular carcinoma.  Gastroenterology. 2004;  44 S268-S276
• 14 Schlitt H J, Neipp M, Weimann A. et al . Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation.  J Clin Oncol. 1999;  44 324-331
• 15 Jonas S, Bechstein W O, Steinmuller T. et al . Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis.  Hepatology. 2001;  44 1080-1086
• 16 Shetty K, Timmins K, Brensinger C. et al . Liver transplantation for hepatocellular carcinoma validation of present selection criteria in predicting outcome.  Liver Transpl. 2004;  44 911-918
• 17 Seufferlein T, Rozengurt E. Rapamycin inhibits constitutive p70s6 k phosphorylation, cell proliferation, and colony formation in small cell lung cancer cells.  Cancer Res. 1996;  44 3895-3897
• 18 Bruix J, Castells A, Bosch J. et al . Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure.  Gastroenterology. 1996;  44 1018-1022
• 19 Jaeck D, Bachellier P, Oussoultzoglou E. et al . Surgical resection of hepatocellular carcinoma. Post-operative outcome and long-term results in Europe: an overview.  Liver Transpl. 2004;  44 S58-S63
• 20 Llovet J M, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation.  Hepatology. 1999;  44 1434-1440
• 21 Schwartz J D, Schwartz M, Mandeli J. et al . Neoadjuvant and adjuvant therapy for resectable hepatocellular carcinoma: review of the randomised clinical trials.  Lancet Oncol. 2002;  44 593-603
• 22 Lencioni R, Cioni D, Crocetti L. et al . Percutaneous ablation of hepatocellular carcinom: a state-of-the-art.  Liver Transpl. 2004;  44 S91-S97
• 23 Omata M, Tateishi R, Yoshida H. et al . Treatment of hepatocellular carcinoma by percutaneous tumor ablation methods: Ethanol injection therapy and radiofrequency ablation.  Gastroenterology. 2004;  44 S159-S166
• 24 Lencioni R, Cioni D, Crocetti L. et al . Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation.  Radiology. 2005;  44 961-967
• 25 Beaugrand M, N’Kontchou G, Seror O. et al . Local/regional and systemic treatments of hepatocellular carcinoma.  Semin Liver Dis. 2005;  44 201-211
• 26 Livraghi T, Giorgio A, Marin G. et al . Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection.  Radiology. 1995;  44 101-108
• 27 Allgaier H P, Deibert P, Olschewski M. et al . Survival benefit of patients with inoperable hepatocellular carcinoma treated by a combination of transarterial chemoembolization and percutaneous ethanol injection-a single-center analysis including 132 patients.  Int J Cancer. 1998;  44 601-605
• 28 Livraghi T, Benedini V, Lazzaroni S. et al . Long term results of single session percutaneous ethanol injection in patients with large hepatocellular carcinoma.  Cancer. 1998;  44 48-57
• 29 Lin S M, Lin C J, Lin C C. et al . Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or = 4 cm.  Gastroenterology. 2004;  44 1714-1723
• 30 Sala M, Llovet J M, Vilana R. et al . Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma.  Hepatology. 2004;  44 1352-1360
• 31 Lencioni R A, Allgaier H P, Cioni D. et al . Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection.  Radiology. 2003;  44 235-240
• 32 Lin S M, Lin C J, Lin C C. et al . Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less.  Gut. 2005;  44 1151-1156
• 33 Lo C M, Ngan H, Tso W K. et al . Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.  Hepatology. 2002;  44 1164-1171
• 34 Llovet J M, Real M I, Montana X. et al . Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.  Lancet. 2002;  44 1734-1739
• 35 Kawai S, Tani M, Okamura J. et al . Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma - a comparison between L-TAE with farmorubicin and L-TAE with adriamycin: preliminary results (second cooperative study). Cooperative Study Group for Liver Cancer Treatment of Japan.  Cancer Chemother Pharmacol. 1994;  44 S97-S102
• 36 Bruix J, Sala M, Llovet J M. Chemoembolization for hepatocellular carcinoma.  Gastroenterology. 2004;  44 S179-S188
• 37 A c omparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire.  N Engl J Med. 1995;  44 1256-1261
• 38 Fuss M, Salter B J, Herman T S. et al . External beam radiation therapy for hepatocellular carcinoma: potential of intensity-modulated and image-guided radiation therapy.  Gastroenterology. 2004;  44 S206-S217
• 39 Seong J, Keum K C, Han K H. et al . Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma.  Int J Radiat Oncol Biol Phys. 1999;  44 393-397
• 40 De Ruyck K, Lambert B, Bacher K. et al . Biologic dosimetry of 188Re-HDD/lipiodol versus 131I-lipiodol therapy in patients with hepatocellular carcinoma.  J Nucl Med. 2004;  44 612-618
• 41 Kennedy A S, Nutting C, Coldwell D. et al . Pathologic response and microdosimetry of (90)Y microspheres in man: review of four explanted whole livers.  Int J Radiat Oncol Biol Phys. 2004;  44 1552-1563
• 42 Ganne-Carrie N, Trinchet J C. Systemic treatment of hepatocellular carcinoma.  Eur J Gastroenterol Hepatol. 2004;  44 275-281
• 43 Schachschal G, Lochs H, Plauth M. Controlled clinical trial of doxorubicin and tamoxifen versus tamoxifen monotherapy in hepatocellular carcinoma.  Eur J Gastroenterol Hepatol. 2000;  44 281-284
• 44 Kubicka S, Rudolph K L, Tietze M K. et al . Phase II study of systemic gemcitabine chemotherapy for advanced unresectable hepatobiliary carcinomas.  Hepatogastroenterology. 2001;  44 783-789
• 45 Lai C L, Wu P C, Chan G C. et al . Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial.  Cancer. 1988;  44 479-483
• 46 Thomas M B, Zhu A X. Hepatocellular carcinoma: the need for progress.  J Clin Oncol. 2005;  44 2892-2899
• 47 Patt Y Z, Hassan M M, Lozano R D. et al . Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2 b for treatment of hepatocellular carcinoma.  J Clin Oncol. 2003;  44 421-427
• 48 Stuart K, Tessitore J, Rudy J. et al . A Phase II trial of nolatrexed dihydrochloride in patients with advanced hepatocellular carcinoma.  Cancer. 1999;  44 410-414
• 49 Barbare J C, Bouche O, Bonnetain F. et al . Randomized Controlled Trial of Tamoxifen in Advanced Hepatocellular Carcinoma.  J Clin Oncol. 2005;  44 4338-4346
• 50 Nowak A K, Chow P K, Findlay M. Systemic therapy for advanced hepatocellular carcinoma: a review.  Eur J Cancer. 2004;  44 1474-1484
• 51 Kouroumalis E, Skordilis P, Thermos K. et al . Treatment of hepatocellular carcinoma with octreotide: a randomised controlled study.  Gut. 1998;  44 442-447
• 52 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. 2002;  44 687-691
• 53 Allgaier H P, Becker G, Olschewski M. et al . Octreotide treatment in patients with advanced hepatocellular carcinoma: First results of the randomized placebo-controlled double-blind HECTOR trial.  Hepatology. 2003;  44 760A
• 54 Patt Y Z, Hassan M M, Lozano R D. et al . Thalidomide in the treatment of patients with hepatocellular carcinoma: a phase II trial.  Cancer. 2005;  44 749-755
• 55 Llovet J M, Sala M, Castells L. et al . Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma.  Hepatology. 2000;  44 54-58
• 56 Kawata S, Yamasaki E, Nagase T. et al . Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial.  Br J Cancer. 2001;  44 886-891
• 57 Butterfield L H. Immunotherapeutic strategies for hepatocellular carcinoma.  Gastroenterology. 2004;  44 S232-S241
• 58 Wada Y, Nakashima O, Kutami R. et al . Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration.  Hepatology. 1998;  44 407-414
• 59 Takayama T, Sekine T, Makuuchi M. et al . Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial.  Lancet. 2000;  44 802-807
• 60 Greten T F. Antibody therapy for the treatment of colon cancer.  Z Gastroenterol. 2004;  44 1413-1415
• 61 Llovet J M, Burroughs A, Bruix J. Hepatocellular carcinoma.  Lancet. 2003;  44 1907-1917