Hepatocellular carcinoma
Carboplatin & Paclitaxel (CP)
CP: Carboplatin & Paclitaxel
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (C) | 1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab |
Inferior EFS |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. This study was conducted in the United States. The reason for the study was that an unanswered question at the time was whether adding an immune checkpoint inhibitor would improve outcomes.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
- Paclitaxel (Taxol) 175 or 200 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
References
- CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02998528
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Section editor | |
---|---|
Neeta K. Venepalli, MD, MBA Chicago, IL |
38 regimens on this page
48 variants on this page
|
Liver cancer or hepatobiliary cancer comprises cancers that arise within the liver and its hepatocytes (hepatocellular carcinoma) and the biliary tract cancers, which include bile duct cancer/cholangiocarcinoma and gallbladder cancer.
Guidelines
ESMO
- Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
NCCN
All lines of therapy
Bevacizumab monotherapy
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Regimen
Study | Evidence |
---|---|
Siegel et al. 2008 | Phase II |
The dose here was a pre-planned escalation dose.
Chemotherapy
- Bevacizumab (Avastin) 10 mg/kg IV once on day 1
14-day cycles
References
- Siegel AB, Cohen EI, Ocean A, Lehrer D, Goldenberg A, Knox JJ, Chen H, Clark-Garvey S, Weinberg A, Mandeli J, Christos P, Mazumdar M, Popa E, Brown RS Jr, Rafii S, Schwartz JD. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol. 2008 Jun 20;26(18):2992-8. link to original article contains verified protocol link to PMC article PubMed
Capecitabine monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Abdel-Rahman et al. 2013 | Randomized Phase II | Sorafenib | Inferior OS |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
21-day cycles
References
- Retrospective: Patt YZ, Hassan MM, Aguayo A, Nooka AK, Lozano RD, Curley SA, Vauthey JN, Ellis LM, Schnirer II, Wolff RA, Charnsangavej C, Brown TD. Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma. Cancer. 2004 Aug 1;101(3):578-86. link to original article PubMed
- Abdel-Rahman O, Abdel-Wahab M, Shaker M, Abdel-Wahab S, Elbassiony M, Ellithy M. Sorafenib versus capecitabine in the management of advanced hepatocellular carcinoma. Med Oncol. 2013 Sep;30(3):655. Epub 2013 Jul 4. link to original article PubMed
Capecitabine & Bevacizumab
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Regimen
Study | Evidence |
---|---|
Hsu et al. 2010 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 800 mg/m2 PO BID on days 1 to 14
- Bevacizumab (Avastin) 7.5 mg/kg IV once on day 1
21-day cycle for 6 or more cycles depending on response
References
- Hsu CH, Yang TS, Hsu C, Toh HC, Epstein RJ, Hsiao LT, Chen PJ, Lin ZZ, Chao TY, Cheng AL. Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced hepatocellular carcinoma. Br J Cancer. 2010 Mar 16;102(6):981-6. Epub 2010 Feb 16. link to original article contains verified protocol link to PMC article PubMed
CapeOx
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CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda (Capecitabine), OXaliplatin
Regimen
Study | Evidence |
---|---|
Boige et al. 2007 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
21-day cycles
References
- Boige V, Raoul JL, Pignon JP, Bouché O, Blanc JF, Dahan L, Jouve JL, Dupouy N, Ducreux M; Fédération Francophone de Cancérologie Digestive. Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial. Br J Cancer. 2007 Oct 8;97(7):862-7. Epub 2007 Sep 18. link to original article contains verified protocol link to PMC article PubMed
Capecitabine, Oxaliplatin, Bevacizumab
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Regimen
Study | Evidence |
---|---|
Sun et al. 2011 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 PO BID on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
- Bevacizumab (Avastin) 5 mg/kg IV once on day 1
- Infusion times are 75 to 105 minutes for the first dose, which if tolerated could be decreased to 50 to 70 minutes for the second dose, then 20 to 40 minutes for dose 3 and later
21-day cycles
References
- Sun W, Sohal D, Haller DG, Mykulowycz K, Rosen M, Soulen MC, Caparro M, Teitelbaum UR, Giantonio B, O'Dwyer PJ, Shaked A, Reddy R, Olthoff K. Phase 2 trial of bevacizumab, capecitabine, and oxaliplatin in treatment of advanced hepatocellular carcinoma. Cancer. 2011 Jul 15;117(14):3187-92. Epub 2011 Jan 24. link to original article contains verified regimen PubMed
Doxorubicin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gish et al. 2007 | Phase III | Nolatrexed | Superior OS |
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
21-day cycles
References
- Gish RG, Porta C, Lazar L, Ruff P, Feld R, Croitoru A, Feun L, Jeziorski K, Leighton J, Gallo J, Kennealey GT. Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin. J Clin Oncol. 2007 Jul 20;25(21):3069-75. link to original article contains verified protocol PubMed
Erlotinib & Bevacizumab
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Regimen
Study | Evidence |
---|---|
Thomas et al. 2009 | Phase II |
Chemotherapy
- Erlotinib (Tarceva) 150 mg PO once per day
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
References
- Thomas MB, Morris JS, Chadha R, Iwasaki M, Kaur H, Lin E, Kaseb A, Glover K, Davila M, Abbruzzese J. Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma. J Clin Oncol. 2009 Feb 20;27(6):843-50. Epub 2009 Jan 12. link to original article contains verified protocol PubMed
Fluorouracil & Folinic acid
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Regimen
Study | Evidence |
---|---|
Porta et al. 1995 | Phase II |
Chemotherapy
- Fluorouracil (5-FU) 370 mg/m2 IV once per day on days 1 to 5
- Folinic acid (Leucovorin) 200 mg/m2 IV once per day on days 1 to 5
28-day cycles
References
- 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. 1995 Nov-Dec;52(6):487-91. link to original article PubMed
GemOx
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GemOx: Gemcitabine, Oxaliplatin
Regimen
Study | Evidence | ORR |
---|---|---|
Louafi et al. 2007 | Phase II | 18% (95% CI 8–34) |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 100 mg/m2 IV over 2 hours once on day 2
14-day cycles, given until progression of disease, unacceptable toxicity, or patient choice
References
- Louafi S, Boige V, Ducreux M, Bonyhay L, Mansourbakht T, de Baere T, Asnacios A, Hannoun L, Poynard T, Taïeb J. Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC): results of a phase II study. Cancer. 2007 Apr 1;109(7):1384-90. link to original article contains verified protocol PubMed
- Retrospective: Zaanan A, Williet N, Hebbar M, Dabakuyo TS, Fartoux L, Mansourbakht T, Dubreuil O, Rosmorduc O, Cattan S, Bonnetain F, Boige V, Taïeb J. Gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma: A large multicenter AGEO study. J Hepatol. 2013 Jan;58(1):81-8. Epub 2012 Sep 16. link to original article PubMed
Nivolumab monotherapy
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Regimen
Study | Evidence | ORR |
---|---|---|
El-Khoueiry et al. 2017 (CheckMate 040) | Phase I/II | 20% (95% CI 15–26) |
This is the dose used in the expansion cohort of this study.
Immunotherapy
- Nivolumab (Opdivo) 3 mg/kg IV once on day 1
14-day cycles
References
- El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. Epub 2017 Apr 20.link to original article contains protocol PubMed
Placebo
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Llovet et al. 2008 (SHARP) | Phase III (C) | Sorafenib | Inferior OS |
Cheng et al. 2008 | Phase III (C) | Sorafenib | Seems to have inferior OS |
Zhu et al. 2015 (REACH) | Phase III (C) | Ramucirumab | Seems not superior |
Bruix et al. 2016 (RESORCE) | Phase III (C) | Regorafenib | Inferior OS |
No active antineoplastic treatment.
References
- Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. link to original article contains verified protocol PubMed
- Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. 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. 2009 Jan;10(1):25-34. Epub 2008 Dec 16. link to original article contains verified protocol PubMed
- Subset analysis: Cheng AL, Guan Z, Chen Z, Tsao CJ, Qin S, Kim JS, Yang TS, Tak WY, Pan H, Yu S, Xu J, Fang F, Zou J, Lentini G, Voliotis D, Kang YK. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: Subset analyses of the phase III Sorafenib Asia-Pacific trial. Eur J Cancer. 2012 Jul;48(10):1452-65. Epub 2012 Jan 10. link to original article contains verified protocol PubMed
- Zhu AX, Park JO, Ryoo BY, Yen CJ, Poon R, Pastorelli D, Blanc JF, Chung HC, Baron AD, Pfiffer TE, Okusaka T, Kubackova K, Trojan J, Sastre J, Chau I, Chang SC, Abada PB, Yang L, Schwartz JD, Kudo M; REACH Trial Investigators. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2015 Jul;16(7):859-70. Epub 2015 Jun 18. link to original article PubMed
- Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, Gerolami R, Masi G, Ross PJ, Song T, Bronowicki JP, Ollivier-Hourmand I, Kudo M, Cheng AL, Llovet JM, Finn RS, LeBerre MA, Baumhauer A, Meinhardt G, Han G; RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Jan 7;389(10064):56-66. Epub 2016 Dec 6. Erratum in: Lancet. 2017 Jan 7;389(10064):36. link to original article contains protocol PubMed
Regorafenib monotherapy
Regorafenib (Stivarga) for hepatocellular carcinoma
Sorafenib monotherapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Abou-Alfa et al. 2006 | Phase II | ||
Llovet et al. 2008 (SHARP) | Phase III | Placebo | Superior OS |
Cheng et al. 2008 | Phase III | Placebo | Seems to have superior OS |
Pinter et al. 2009 | Retrospective | ||
Abdel-Rahman et al. 2013 | Randomized Phase II | Capecitabine | Superior OS |
Vilgrain et al. 2017 (SARAH) | Phase III | SIRT | Seems not superior |
Chemotherapy
- Sorafenib (Nexavar) 400 mg PO BID
- Dose/schedule changes due to toxicity include 400 mg PO once per day, 400 mg PO every other day, 200 mg PO BID, 200 mg PO once per day
Given until progression of disease or unacceptable toxicity
References
- Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2006 Sep 10;24(26):4293-300. Epub 2006 Aug 14. link to original article contains verified protocol PubMed
- Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. link to original article contains verified protocol PubMed
- Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. 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. 2009 Jan;10(1):25-34. Epub 2008 Dec 16. link to original article contains verified protocol PubMed
- Subset analysis: Cheng AL, Guan Z, Chen Z, Tsao CJ, Qin S, Kim JS, Yang TS, Tak WY, Pan H, Yu S, Xu J, Fang F, Zou J, Lentini G, Voliotis D, Kang YK. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: Subset analyses of the phase III Sorafenib Asia-Pacific trial. Eur J Cancer. 2012 Jul;48(10):1452-65. Epub 2012 Jan 10. link to original article contains verified protocol PubMed
- Retrospective: Pinter M, Sieghart W, Graziadei I, Vogel W, Maieron A, Königsberg R, Weissmann A, Kornek G, Plank C, Peck-Radosavljevic M. Sorafenib in unresectable hepatocellular carcinoma from mild to advanced stage liver cirrhosis. Oncologist. 2009 Jan;14(1):70-6. Epub 2009 Jan 14. link to original article PubMed
- Abdel-Rahman O, Abdel-Wahab M, Shaker M, Abdel-Wahab S, Elbassiony M, Ellithy M. Sorafenib versus capecitabine in the management of advanced hepatocellular carcinoma. Med Oncol. 2013 Sep;30(3):655. Epub 2013 Jul 4. link to original article PubMed
- Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca AD, Pageaux GP, Sibert A, Bouattour M, Lebtahi R, Allaham W, Barraud H, Laurent V, Mathias E, Bronowicki JP, Tasu JP, Perdrisot R, Silvain C, Gerolami R, Mundler O, Seitz JF, Vidal V, Aubé C, Oberti F, Couturier O, Brenot-Rossi I, Raoul JL, Sarran A, Costentin C, Itti E, Luciani A, Adam R, Lewin M, Samuel D, Ronot M, Dinut A, Castera L, Chatellier G; SARAH Trial Group. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1624-1636. Epub 2017 Oct 26. link to original article contains protocol PubMed
Sunitinib monotherapy
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Regimen
Study | Evidence |
---|---|
Zhu et al. 2009 | Phase II |
Chemotherapy
- Sunitinib (Sutent) 37.5 mg PO once per day on days 1 to 28
- Dose can be reduced to 25 and 12.5 mg once per day depending on toxicity
42-day cycles
References
- Zhu AX, Sahani DV, Duda DG, di Tomaso E, Ancukiewicz M, Catalano OA, Sindhwani V, Blaszkowsky LS, Yoon SS, Lahdenranta J, Bhargava P, Meyerhardt J, Clark JW, Kwak EL, Hezel AF, Miksad R, Abrams TA, Enzinger PC, Fuchs CS, Ryan DP, Jain RK. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol. 2009 Jun 20;27(18):3027-35. Epub 2009 May 26. link to original article contains verified protocol link to PMC article PubMed
TACE, then 5-FU
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TACE: Trans-Arterial ChemoEmbolization
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kawata et al. 2001 | Phase III | TACE, then 5-FU & Pravastatin | Inferior OS |
Chemotherapy, TACE portion
- Doxorubicin (Adriamycin) 30 mg IA once, given first
- Gelatin-sponge particles and ethyl ester of poppyseed oil fatty acids containing 38% iodine by weight (Lipiodol; AndreGelbe Laboratories, Paris, France)
One course, followed in 2 weeks by:
Chemotherapy
- Fluorouracil (5-FU) 200 mg PO once per day
2-month course
References
- Kawata S, Yamasaki E, Nagase T, Inui Y, Ito N, Matsuda Y, Inada M, Tamura S, Noda S, Imai Y, Matsuzawa Y. Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. Br J Cancer. 2001 Apr 6;84(7):886-91. contains verified protocol link to PMC article PubMed