Hepatocellular carcinoma - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main HCC page for current regimens.
Last updated on 2024-07-23:4 regimens on this page
7 variants on this page
 
=First-line therapy for advanced or metastatic disease=
==Capecitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Abdel-Rahman et al. 2013	2010-2011 	Randomized Phase 2 (E-switch-ooc)	Sorafenib 	Shorter PFS (primary endpoint)
Note: Neither the primary outcome (progression-free survival) or secondary outcome (overall survival) were met. 
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day 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 EuroPMC
#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 EuroPMC
==Nivolumab monotherapy==
===Regimen variant #1, weight-based===
Study 	Dates of enrollment	Evidence 	Efficacy
El-Khoueiry et al. 2017 (CheckMate 040)	2012-2016 	Phase 1/2 (RT)	ORR: 20% (95% CI, 15–26)
Note: This was the dose used in the expansion cohort of this study; patients were required to have ECOG PS 1 or less, and Child-Pugh scores of 6 or less (Child-Pugh A) for the dose expansion. 68% of patients in the dose expansion phase received prior sorafenib therapy.
====Immunotherapy====
*Nivolumab (Opdivo) 3 mg/kg IV once on day 1
14-day cycles
===Regimen variant #2, flat dosing===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Yau et al. 2021 (CheckMate 459)	2016-01-11 to 2017-05-24	Phase 3 (E-switch-ooc)	Sorafenib 	Might have longer OS (primary endpoint)Median OS: 16.4 vs 14.7 mo(HR 0.85, 95% CI 0.72-1.02)
Note: Study included patients with Child-Pugh class B (5-9), hepatitis B and C infections. This study was the basis for the withdrawal of FDA approval for this indication.
====Immunotherapy====
*Nivolumab (Opdivo) 240 mg IV once on day 1
14-day cycles
===References===
#CheckMate 040: El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH 3rd, 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 dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT01658878
##Update: El-Khoueiry AB, Trojan J, Meyer T, Yau T, Melero I, Kudo M, Hsu C, Kim TY, Choo SP, Kang YK, Yeo W, Chopra A, Soleymani S, Yao J, Neely J, Tschaika M, Welling TH, Sangro B. Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040. Ann Oncol. 2024 Apr;35(4):381-391. Epub 2023 Dec 25. link to original article EuroPMC
#CheckMate 459: Yau T, Park JW, Finn RS, Cheng AL, Mathurin P, Edeline J, Kudo M, Harding JJ, Merle P, Rosmorduc O, Wyrwicz L, Schott E, Choo SP, Kelley RK, Sieghart W, Assenat E, Zaucha R, Furuse J, Abou-Alfa GK, El-Khoueiry AB, Melero I, Begic D, Chen G, Neely J, Wisniewski T, Tschaika M, Sangro B. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022 Jan;23(1):77-90. Epub 2021 Dec 13. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT02576509
==Sunitinib monotherapy==
===Regimen variant #1, interrupted sunitinib===
Study 	Dates of enrollment 	Evidence
Zhu et al. 2009 (DF/HCC 05-348)	2006 to not reported	Phase 2
====Targeted therapy====
*Sunitinib (Sutent) 37.5 mg PO once per day on days 1 to 28
42-day cycles
===Regimen variant #2, continuous sunitinib===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Cheng et al. 2013 (SUN 1170)	2008-2010 	Phase 3 (E-switch-ic)	Sorafenib 	Shorter OS (primary endpoint)Median OS: 7.9 vs 10.2 mo(HR 1.30, 95% CI 1.13-1.50)
Note: Early trial termination of SUN 1170 occurred for futility and safety reasons; sunitinib treated patients demonstrated inferior OS and more frequent and severe toxicities. Dosing preserved for historical context. 
====Targeted therapy====
*Sunitinib (Sutent) 37.5 mg PO once per day on days 1 to 28
28-day cycles
====Dose and schedule modifications====
*Dose can be reduced to 25 and 12.5 mg once per day depending on toxicity
===References===
# DF/HCC 05-348: 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00361309
# SUN 1170: Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, Chung HC, Song X, Xu J, Poggi G, Omata M, Pitman Lowenthal S, Lanzalone S, Yang L, Lechuga MJ, Raymond E. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol. 2013 Nov 10;31(32):4067-75. Epub 2013 Sep 30. link to original article EuroPMC NCT00699374
==Tamoxifen monotherapy==
===Regimen variant #1, 20 mg/day===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Barbare et al. 2005 (FFCD 9403)	1995-2000 	Phase 3 (E-esc)	Best supportive care 	Did not meet primary endpoint of OS
Doffoël et al. 2008 (FFCD 9402)	1995-2002 	Phase 3 (C) 	TACE & Tamoxifen 	Did not meet primary endpoint of OS
Verset et al. 2007 	2001-2005 	Phase 3 (C) 	Octreotide LAR & Tamoxifen	Did not meet primary endpoint of OSMedian OS: 6 vs 3 mo(HR not reported)
====Endocrine therapy====
*Tamoxifen (Nolvadex) 20 mg PO once per day
Continued indefinitely
===Regimen variant #2, 40 mg/day===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gallo et al. 1998 (CLIP-1)	1995-1997 	Phase 3 (E-esc)	Best supportive care	Did not meet primary endpoint of OS
====Endocrine therapy====
*Tamoxifen (Nolvadex) 40 mg PO once per day
Continued indefinitely
===References===
# CLIP-1: Gallo C, Daniele B, Gaeta GB, Perrone F, Pignata S; CLIP. Tamoxifen in treatment of hepatocellular carcinoma: a randomised controlled trial. Lancet. 1998 Jul 4;352(9121):17-20. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# FFCD 9403: Barbare JC, Bouché O, Bonnetain F, Raoul JL, Rougier P, Abergel A, Boige V, Denis B, Blanchi A, Pariente A, Milan C, Bedenne L. Randomized controlled trial of tamoxifen in advanced hepatocellular carcinoma. J Clin Oncol. 2005 Jul 1;23(19):4338-46. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Verset G, Verslype C, Reynaert H, Borbath I, Langlet P, Vandebroek A, Peeters M, Houbiers G, Francque S, Arvanitakis M, Van Laethem JL. Efficacy of the combination of long-acting release octreotide and tamoxifen in patients with advanced hepatocellular carcinoma: a randomised multicentre phase III study. Br J Cancer. 2007 Sep 3;97(5):582-8. Epub 2007 Aug 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
# FFCD 9402: Doffoël M, Bonnetain F, Bouché O, Vetter D, Abergel A, Fratté S, Grangé JD, Stremsdoerfer N, Blanchi A, Bronowicki JP, Caroli-Bosc FX, Causse X, Masskouri F, Rougier P, Bedenne L; Fédération Francophone de Cancérologie Digestive. Multicentre randomised phase III trial comparing Tamoxifen alone or with transarterial Lipiodol Chemoembolisation for unresectable hepatocellular carcinoma in cirrhotic patients (Fédération Francophone de Cancérologie Digestive 9402). Eur J Cancer. 2008 Mar;44(4):528-38. Epub 2008 Jan 31. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
Category:Hepatocellular carcinoma regimens
Category:Historical regimens
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Category:Hepatobiliary cancers