Difference between revisions of "Hepatocellular carcinoma"
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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]]. | Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]]. | ||
{| class="wikitable" style="text-align:center; width:50%;" | {| class="wikitable" style="text-align:center; width:50%;" | ||
− | ! | + | ! style="color:white; font-size:125%; background-color:#08519c" align="center" colspan="2" |'''Section editor''' |
|- | |- | ||
| style="background-color:#F0F0F0" |[[File:nkv.jpg|frameless|upright=0.3|center]] | | style="background-color:#F0F0F0" |[[File:nkv.jpg|frameless|upright=0.3|center]] | ||
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=Local therapy= | =Local therapy= | ||
− | + | Concurrent TACE plus Sorafenib | |
+ | {| class="wikitable" style="width: 100%; text-align:center;" | ||
+ | !Study | ||
+ | ![[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !Comparator | ||
+ | ![[Levels_of_Evidence#Efficacy|Efficacy]] | ||
+ | |- | ||
+ | |Meyer et al 2017 (TACE 2) http://www.thelancet.com/journals/langas/article/PIIS2468-1253(17)30156-5/abstract | ||
+ | | style="background-color:#1a9851" |Phase III | ||
+ | |[[#Sorafenib_monotherapy|TACE plus placebo]] | ||
+ | | style="background-color:#d73027" |Did not meet primary outcome of improved PFS | ||
+ | |- | ||
+ | | | ||
+ | | | ||
+ | | | ||
+ | | | ||
+ | |} | ||
+ | This European study assessed the addition of concurrent sorafenib to DEB-TACE; patients had Child-Pugh A liver disease, and ECOG PS 0 or 1. | ||
+ | |||
+ | ====Chemotherapy==== | ||
+ | *[[Sorafenib (Nexavar)]] 400 mg PO BID | ||
+ | |||
+ | '''28-day cycles''' | ||
+ | |||
+ | ===References=== | ||
+ | # Meyer T, Fox R, Ma YT, Ross P,J, James MW, Sturgess R, Stubbs C, Stocken DD, Wall L, Watkinson A, Hacking N, Evans TRJ, Collins P, Hubner RA, Cunningham D, Primrose JN, Johnson PJ, Palmer DH. Sorafenib in combination with transarterial chemoembolization in patients with unresectable hepatocellular carcimoma (TACE2): a randomized placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):565-575. doi: 10.1016/S2468-1253(17)30156-5. Epub 2017 Jun 23. | ||
+ | TACE followed by Sorafenib | ||
+ | {| class="wikitable" style="width: 100%; text-align:center;" | ||
+ | !Study | ||
+ | ![[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !Comparator | ||
+ | ![[Levels_of_Evidence#Efficacy|Efficacy]] | ||
+ | |- | ||
+ | |Kudo et al, 2011 doi: 10.1016/j.ejca.2011.05.007. | ||
+ | | style="background-color:#1a9851" |Phase III | ||
+ | |TACE followed by placebo | ||
+ | | style="background-color:#d73027" |Did not meet primary outcome of improved TTP | ||
+ | |- | ||
+ | | | ||
+ | | | ||
+ | | | ||
+ | | | ||
+ | |} | ||
+ | This Japanese and Korean study including patients with Child-Pugh A cirrhosis with a primary endpoint of TTP, and secondary endpoint of OS. More than 50% of patients started sorafenib after 9 weeks post TACE. 73% of patients had dose reductions, and 91% of patients had dose interruptions. | ||
+ | |||
+ | ====Chemotherapy==== | ||
+ | *[[Sorafenib (Nexavar)]] 400 mg PO BID | ||
+ | |||
+ | '''28-day cycles''' | ||
+ | |||
+ | ===References=== | ||
+ | # Kudo M, Imanaka K, Chida N, Nakachi K, Tak WY, Takayama T, Yoon JH, Hori T, Kumada H, Hayashi N, Kaneko S, Tsubouchi H, Suh DJ, Furuse J, Okusaka T, Tanaka K, Matsui O, Wada M, Yamaguchi I, Ohya T, Meinhardt G, Okita K. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer. 2011 Sep;47(14):2117-27. doi: 10.1016/j.ejca.2011.05.007. | ||
+ | |||
+ | Radioembolization | ||
+ | |||
+ | Regimen {{#subobject:34d254|Variant=1}} | ||
+ | {| class="wikitable" style="width: 100%; text-align:center;" | ||
+ | !Study | ||
+ | ![[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !Comparator | ||
+ | ![[Levels_of_Evidence#Efficacy|Efficacy]] | ||
+ | |- | ||
+ | |Chow et al, 2017 (SIRveNIB) http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.4002 | ||
+ | | style="background-color:#1a9851" |Phase III | ||
+ | |[[#Sorafenib_monotherapy|Sorafenib]] | ||
+ | | style="background-color:#d73027" |Did not meet primary outcome of improved OS | ||
+ | |- | ||
+ | |Vilgrain et al, 2017 (SARAH) http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30683-6/abstract | ||
+ | |Phase III | ||
+ | |[[#Sorafenib_monotherapy|Sorafenib]] | ||
+ | |Did not meet primary outcome of improved OS | ||
+ | |} | ||
+ | ''Chow et al, 2017: This multicenter Asian study randomized newly diagnosed patients with locally advanced inoperable HCC to a single injection of Y90 or sorafenib until progressive disease or unacceptable toxicity. Primary endpoint of improved OS was not met; Y90 was associated with higher ORR, few SAE, and similar OS, similar OS and DCR.'' | ||
+ | |||
+ | ''Vilgrain et al, 2017: This multicenter European study also included patients without two unsuccessful rounds of TACE. Primary endpoint of improved OS was not met; Y90 was associated with higher ORR, lower DCR, fewer AE, and similar survival.'' | ||
+ | |||
+ | ====Chemotherapy==== | ||
+ | *[[Sorafenib (Nexavar)]] 400 mg PO BID | ||
+ | |||
+ | '''28-day cycles''' | ||
+ | |||
+ | ===References=== | ||
+ | # Chow PHW, Gandhi M. Phase III multi-centre open-label randomized controlled trial of selective internal radiation therapy (SIRT) versus sorafenib in locally advanced hepatocellular carcinoma: The SIRveNIB study (abstract). J Clin Oncol 35, 2017 suppl; abstr 4002). Abstract available online at http://abstracts.asco.org/199/AbstView_199_187604.html | ||
+ | # Vilgrain V, Pereira H, Assenat E, et al. 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 randomized controlled phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1624-1636. doi: 10.1016/S1470-2045(17)30683-6. Epub 2017 Oct 26. | ||
+ | |||
=First-line therapy= | =First-line therapy= | ||
''Note: in this setting, first-line refers to first-line systemic therapy; many patients had resection, ablation, and/or TACE prior to systemic therapy. See individual trials for details.'' | ''Note: in this setting, first-line refers to first-line systemic therapy; many patients had resection, ablation, and/or TACE prior to systemic therapy. See individual trials for details.'' | ||
Line 40: | Line 124: | ||
|- | |- | ||
|} | |} | ||
− | ''The dose here was a pre-planned escalation dose with initial dose of 5mg/kg.'' | + | ''The dose here was a pre-planned escalation dose with initial dose of 5mg/kg. The study met and exceeded primary endpoint of determining whether bevacizumab improved 6 month PFS from 40-60% (observed 6 months PFS was 65%).'' |
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1 | ||
Line 171: | Line 255: | ||
| style="background-color:#1a9851" |Phase III | | style="background-color:#1a9851" |Phase III | ||
|[[#FOLFOX4|FOLFOX4]] | |[[#FOLFOX4|FOLFOX4]] | ||
− | |style="background-color:#fee08b"| | + | | style="background-color:#fee08b" |Trend towards inferior OS |
|- | |- | ||
|} | |} | ||
''EACH included patients with both Child-Pugh stage A and B disease (AST or ALT less than 2.5x ULN, T bil less than 1.5x ULN, INR less than 1.5).'' | ''EACH included patients with both Child-Pugh stage A and B disease (AST or ALT less than 2.5x ULN, T bil less than 1.5x ULN, INR less than 1.5).'' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | + | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 (Gish et al 2007) |
**Gish et al 2007: Initial dose reduction to 30 mg/m<sup>2</sup> IV for patients with T bil <u>greater than</u> 1.2mg/dL | **Gish et al 2007: Initial dose reduction to 30 mg/m<sup>2</sup> IV for patients with T bil <u>greater than</u> 1.2mg/dL | ||
+ | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 (Qin et al 2013) | ||
'''21-day cycles''' | '''21-day cycles''' | ||
Line 252: | Line 337: | ||
| style="background-color:#1a9851" |Phase III | | style="background-color:#1a9851" |Phase III | ||
|[[#Doxorubicin_monotherapy|Doxorubicin]] | |[[#Doxorubicin_monotherapy|Doxorubicin]] | ||
− | | style="background-color:#d9ef8b"|Might have superior OS | + | | style="background-color:#d9ef8b" |Might have superior OS |
|} | |} | ||
''This study included patients with both Child-Pugh stage A and B disease (AST or ALT less than 2.5x ULN, T bil less than 1.5x ULN, INR less than 1.5).'' | ''This study included patients with both Child-Pugh stage A and B disease (AST or ALT less than 2.5x ULN, T bil less than 1.5x ULN, INR less than 1.5).'' | ||
Line 416: | Line 501: | ||
!Study | !Study | ||
![[Levels_of_Evidence#Evidence|Evidence]] | ![[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !Comparator | ||
+ | ![[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
− | | | + | |Cheng et al. 2013 |
− | | style="background-color:# | + | | style="background-color:#1a9851" |Phase III (C) |
− | |- | + | |[[#Sorafenib_monotherapy|Sorafenib]] |
+ | | style="background-color:#d73027" |Inferior OS | ||
|} | |} | ||
− | == | + | ''Early trial termination occurred for futility and safety reasons; sunitinib treated patients demonstrated inferior OS and more frequent and severe toxicities.'' |
− | + | {| class="wikitable" style="width: 100%; text-align:center;" | |
− | |||
− | + | |} | |
===References=== | ===References=== | ||
− | # | + | # 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. doi: 10.1200/JCO.2012.45.8372. Epub 2013 Sep 30. |
==TACE, then 5-FU {{#subobject:572d2d|Regimen=1}}== | ==TACE, then 5-FU {{#subobject:572d2d|Regimen=1}}== | ||
Line 448: | Line 535: | ||
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
+ | | | ||
|} | |} | ||
====Chemotherapy, TACE portion==== | ====Chemotherapy, TACE portion==== | ||
Line 479: | Line 567: | ||
| style="background-color:#1a9851" |Phase III | | style="background-color:#1a9851" |Phase III | ||
|[[#FOLFOX4_2|FOLFOX4]] | |[[#FOLFOX4_2|FOLFOX4]] | ||
− | |style="background-color:#fee08b"| | + | | style="background-color:#fee08b" |Trend toward inferior OS |
|- | |- | ||
|} | |} | ||
− | ''EACH included patients with both Child-Pugh stage A and B disease (AST or ALT | + | ''The EACH study required evidence of HBV or HCV with cirrhosis, and included patients with both Child-Pugh stage A and B disease (AST or ALT < 2.5x ULN, T bil < than 1.5x ULN, INR < 1.5 ULN; patients with AST and ALT < 5x ULN were included if T bil was within normal limits).'' |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 |
'''21-day cycles''' | '''21-day cycles''' | ||
Line 506: | Line 594: | ||
| style="background-color:#1a9851" |Phase III | | style="background-color:#1a9851" |Phase III | ||
|[[#Doxorubicin_monotherapy_2|Doxorubicin]] | |[[#Doxorubicin_monotherapy_2|Doxorubicin]] | ||
− | | style="background-color:#d9ef8b"| | + | | style="background-color:#d9ef8b" |Trend towards superior OS |
|} | |} | ||
− | '' | + | ''The EACH study required evidence of HBV or HCV with cirrhosis, and included patients with both Child-Pugh stage A and B disease (AST or ALT < 2.5x ULN, T bil < than 1.5x ULN, INR < 1.5 ULN; patients with AST and ALT < 5x ULN were included if T bil was within normal limits).'' |
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus at hour 2, then 600 mg/m<sup>2</sup> over 22 hours on days 1 and 2 (total dose per cycle: 2000 mg/m<sup>2</sup>) | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus at hour 2, then 600 mg/m<sup>2</sup> over 22 hours on days 1 and 2 (total dose per cycle: 2000 mg/m<sup>2</sup>) | ||
Line 527: | Line 615: | ||
!Study | !Study | ||
![[Levels_of_Evidence#Evidence|Evidence]] | ![[Levels_of_Evidence#Evidence|Evidence]] | ||
− | |[[Overall response rate|'''ORR''']] | + | |[[Overall response rate|'''ORR''']] '''(dose expansion phase)''' |
|- | |- | ||
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31046-2/abstract El-Khoueiry et al. 2017 (CheckMate 040)] | |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31046-2/abstract El-Khoueiry et al. 2017 (CheckMate 040)] | ||
Line 534: | Line 622: | ||
|- | |- | ||
|} | |} | ||
− | ''This is 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.'' | + | ''This is 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; Child-Pugh B7 patients were eligible for the dose-escalation phase. Patients with HBV infection were required to be receiving effective antiviral therapy (viral load < 100 IU/mL). 68% of patients in the dose expansion phase received prior sorafenib therapy.'' |
====Immunotherapy==== | ====Immunotherapy==== | ||
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1 | *[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1 | ||
Line 569: | Line 657: | ||
| style="background-color:#1a9851" |Phase III (C) | | style="background-color:#1a9851" |Phase III (C) | ||
|Everolimus | |Everolimus | ||
− | |style="background-color:#ffffbf" |Did not meet primary outcome of improved overall survival | + | | style="background-color:#ffffbf" |Did not meet primary outcome of improved overall survival |
|} | |} | ||
Line 580: | Line 668: | ||
==Regorafenib monotherapy {{#subobject:3c587e|Regimen=1}}== | ==Regorafenib monotherapy {{#subobject:3c587e|Regimen=1}}== | ||
− | {{#subobject: | + | '''Regimen''' {{#subobject:1c2329|Variant=1}} |
− | { | + | {| class="wikitable" style="width: 100%; text-align:center;" |
+ | !Study | ||
+ | ![[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !Comparator | ||
+ | ![[Levels_of_Evidence#Efficacy|Efficacy]] | ||
+ | |- | ||
+ | |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32453-9/fulltext Bruix et al. 2016 (RESORCE)] | ||
+ | | style="background-color:#1a9851" |Phase III | ||
+ | |Placebo | ||
+ | | style="background-color:#d9ef8b" |Superior OS | ||
+ | |} | ||
+ | ''The RESORCE study required patients with sorafenib tolerance <u>></u> 400mg/day <u>></u> 20 days of the last 28 days of treatment, and who were ECOS PG 0-1, and with Child-Pugh A status.'' | ||
+ | '''Chemotherapy''' | ||
+ | *Regorafenib (Stivarga) 160 mg PO once per day on days 1 to 21 | ||
+ | '''28 Day Cycles''' | ||
+ | |||
+ | '''References''' | ||
+ | # 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32453-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27932229 PubMed] | ||
[[Category:Hepatocellular carcinoma regimens]] | [[Category:Hepatocellular carcinoma regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Gastrointestinal cancers]] | [[Category:Gastrointestinal cancers]] |
Revision as of 19:05, 19 February 2018
Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer. If this is your first time visiting, we suggest you read the tutorial.
Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.
Section editor | |
---|---|
Neeta K. Venepalli, MD, MBA Chicago, IL |
38 regimens on this page
48 variants on this page
|
Guidelines
ESMO
- 2012: Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
NCCN
Local therapy
Concurrent TACE plus Sorafenib
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Meyer et al 2017 (TACE 2) http://www.thelancet.com/journals/langas/article/PIIS2468-1253(17)30156-5/abstract | Phase III | TACE plus placebo | Did not meet primary outcome of improved PFS |
This European study assessed the addition of concurrent sorafenib to DEB-TACE; patients had Child-Pugh A liver disease, and ECOG PS 0 or 1.
Chemotherapy
- Sorafenib (Nexavar) 400 mg PO BID
28-day cycles
References
- Meyer T, Fox R, Ma YT, Ross P,J, James MW, Sturgess R, Stubbs C, Stocken DD, Wall L, Watkinson A, Hacking N, Evans TRJ, Collins P, Hubner RA, Cunningham D, Primrose JN, Johnson PJ, Palmer DH. Sorafenib in combination with transarterial chemoembolization in patients with unresectable hepatocellular carcimoma (TACE2): a randomized placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):565-575. doi: 10.1016/S2468-1253(17)30156-5. Epub 2017 Jun 23.
TACE followed by Sorafenib
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kudo et al, 2011 doi: 10.1016/j.ejca.2011.05.007. | Phase III | TACE followed by placebo | Did not meet primary outcome of improved TTP |
This Japanese and Korean study including patients with Child-Pugh A cirrhosis with a primary endpoint of TTP, and secondary endpoint of OS. More than 50% of patients started sorafenib after 9 weeks post TACE. 73% of patients had dose reductions, and 91% of patients had dose interruptions.
Chemotherapy
- Sorafenib (Nexavar) 400 mg PO BID
28-day cycles
References
- Kudo M, Imanaka K, Chida N, Nakachi K, Tak WY, Takayama T, Yoon JH, Hori T, Kumada H, Hayashi N, Kaneko S, Tsubouchi H, Suh DJ, Furuse J, Okusaka T, Tanaka K, Matsui O, Wada M, Yamaguchi I, Ohya T, Meinhardt G, Okita K. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer. 2011 Sep;47(14):2117-27. doi: 10.1016/j.ejca.2011.05.007.
Radioembolization
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Chow et al, 2017 (SIRveNIB) http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.4002 | Phase III | Sorafenib | Did not meet primary outcome of improved OS |
Vilgrain et al, 2017 (SARAH) http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30683-6/abstract | Phase III | Sorafenib | Did not meet primary outcome of improved OS |
Chow et al, 2017: This multicenter Asian study randomized newly diagnosed patients with locally advanced inoperable HCC to a single injection of Y90 or sorafenib until progressive disease or unacceptable toxicity. Primary endpoint of improved OS was not met; Y90 was associated with higher ORR, few SAE, and similar OS, similar OS and DCR.
Vilgrain et al, 2017: This multicenter European study also included patients without two unsuccessful rounds of TACE. Primary endpoint of improved OS was not met; Y90 was associated with higher ORR, lower DCR, fewer AE, and similar survival.
Chemotherapy
- Sorafenib (Nexavar) 400 mg PO BID
28-day cycles
References
- Chow PHW, Gandhi M. Phase III multi-centre open-label randomized controlled trial of selective internal radiation therapy (SIRT) versus sorafenib in locally advanced hepatocellular carcinoma: The SIRveNIB study (abstract). J Clin Oncol 35, 2017 suppl; abstr 4002). Abstract available online at http://abstracts.asco.org/199/AbstView_199_187604.html
- Vilgrain V, Pereira H, Assenat E, et al. 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 randomized controlled phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1624-1636. doi: 10.1016/S1470-2045(17)30683-6. Epub 2017 Oct 26.
First-line therapy
Note: in this setting, first-line refers to first-line systemic therapy; many patients had resection, ablation, and/or TACE prior to systemic therapy. See individual trials for details.
Bevacizumab monotherapy
back to top |
Regimen
Study | Evidence |
---|---|
Siegel et al. 2008 | Phase II |
The dose here was a pre-planned escalation dose with initial dose of 5mg/kg. The study met and exceeded primary endpoint of determining whether bevacizumab improved 6 month PFS from 40-60% (observed 6 months PFS was 65%).
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
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Abdel-Rahman et al. 2013 | Randomized Phase II | Sorafenib | Inferior OS |
Neither the primary outcome (progression-free survival) or secondary outcome (overall survival) were met.
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
back to top |
CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda (Capecitabine), OXaliplatin
Regimen
Study | Evidence |
---|---|
Boige et al. 2007 (FFCD 03-03) | 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 protocol PubMed
Doxorubicin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gish et al. 2007 | Phase III | Nolatrexed | Superior OS |
Qin et al. 2013 (EACH) | Phase III | FOLFOX4 | Trend towards inferior OS |
EACH included patients with both Child-Pugh stage A and B disease (AST or ALT less than 2.5x ULN, T bil less than 1.5x ULN, INR less than 1.5).
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1 (Gish et al 2007)
- Gish et al 2007: Initial dose reduction to 30 mg/m2 IV for patients with T bil greater than 1.2mg/dL
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1 (Qin et al 2013)
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
- Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, Lee JH, Sun Y. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013 Oct 1;31(28):3501-8. Epub 2013 Aug 26. link to original article contains verified protocol PubMed
Erlotinib & Bevacizumab
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Regimen
Study | Evidence |
---|---|
Thomas et al. 2009 | Phase II |
Philip et al. 2011 | Phase II |
Patients in Thomas et al. 2009 could have up to one prior systemic treatment.
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
- Philip PA, Mahoney MR, Holen KD, Northfelt DW, Pitot HC, Picus J, Flynn PJ, Erlichman C. Phase 2 study of bevacizumab plus erlotinib in patients with advanced hepatocellular cancer. Cancer. 2012 May 1;118(9):2424-30. Epub 2011 Sep 27. link to original article link to PMC article 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
FOLFOX4
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FOLFOX4: FOLinic acid, Fluorouracil, OXaliplatin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Qin et al. 2013 (EACH) | Phase III | Doxorubicin | Might have superior OS |
This study included patients with both Child-Pugh stage A and B disease (AST or ALT less than 2.5x ULN, T bil less than 1.5x ULN, INR less than 1.5).
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus at hour 2, then 600 mg/m2 over 22 hours on days 1 and 2 (total dose per cycle: 2000 mg/m2)
- Folinic acid (Leucovorin) 200 mg/m2 IV hour 0 to hour 2 once per day on days 1 and 2
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycles
References
- Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, Lee JH, Sun Y. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013 Oct 1;31(28):3501-8. Epub 2013 Aug 26. link to original article contains verified protocol 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; 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
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. 2009 | Phase III (C) | Sorafenib | No predetermined endpoint; seems superior |
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
Sorafenib monotherapy
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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 | Comparator | Efficacy |
---|---|---|---|
Cheng et al. 2013 | Phase III (C) | Sorafenib | Inferior OS |
Early trial termination occurred for futility and safety reasons; sunitinib treated patients demonstrated inferior OS and more frequent and severe toxicities.
References
- 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. doi: 10.1200/JCO.2012.45.8372. Epub 2013 Sep 30.
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
Subsequent lines of therapy
Doxorubicin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Qin et al. 2013 (EACH) | Phase III | FOLFOX4 | Trend toward inferior OS |
The EACH study required evidence of HBV or HCV with cirrhosis, and included patients with both Child-Pugh stage A and B disease (AST or ALT < 2.5x ULN, T bil < than 1.5x ULN, INR < 1.5 ULN; patients with AST and ALT < 5x ULN were included if T bil was within normal limits).
Chemotherapy
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
21-day cycles
References
- Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, Lee JH, Sun Y. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013 Oct 1;31(28):3501-8. Epub 2013 Aug 26. link to original article contains verified protocol PubMed
FOLFOX4
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FOLFOX4: FOLinic acid, Fluorouracil, OXaliplatin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Qin et al. 2013 (EACH) | Phase III | Doxorubicin | Trend towards superior OS |
The EACH study required evidence of HBV or HCV with cirrhosis, and included patients with both Child-Pugh stage A and B disease (AST or ALT < 2.5x ULN, T bil < than 1.5x ULN, INR < 1.5 ULN; patients with AST and ALT < 5x ULN were included if T bil was within normal limits).
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus at hour 2, then 600 mg/m2 over 22 hours on days 1 and 2 (total dose per cycle: 2000 mg/m2)
- Folinic acid (Leucovorin) 200 mg/m2 IV hour 0 to hour 2 once per day on days 1 and 2
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycles
References
- Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, Lee JH, Sun Y. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013 Oct 1;31(28):3501-8. Epub 2013 Aug 26. link to original article contains verified protocol PubMed
Nivolumab monotherapy
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Regimen
Study | Evidence | ORR (dose expansion phase) |
---|---|---|
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; 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; Child-Pugh B7 patients were eligible for the dose-escalation phase. Patients with HBV infection were required to be receiving effective antiviral therapy (viral load < 100 IU/mL). 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
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 |
---|---|---|---|
Zhu et al. 2015 (REACH) | Phase III (C) | Ramucirumab | Did not meet primary outcome of improved overall survival |
Bruix et al. 2016 (RESORCE) | Phase III (C) | Regorafenib | Inferior OS |
Zhu et al. 2014 (EVOLVE-1) | Phase III (C) | Everolimus | Did not meet primary outcome of improved overall survival |
No active antineoplastic treatment.
References
- 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
- Zhu AX, Kudo M, Assenat E, Cattan S, Kang YK, Lim HY, Poon RT, Blanc JF, Vogel A, Chen CL, Dorval E, Peck-Radosavljevic M, Santoro A, Daniele B, Furuse J, Jappe A, Perraud K, Anak O, Sellami DB, Chen LT. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA. 2014 Jul 2;312(1):57-67. link to original article PubMed
Regorafenib monotherapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bruix et al. 2016 (RESORCE) | Phase III | Placebo | Superior OS |
The RESORCE study required patients with sorafenib tolerance > 400mg/day > 20 days of the last 28 days of treatment, and who were ECOS PG 0-1, and with Child-Pugh A status.
Chemotherapy
- Regorafenib (Stivarga) 160 mg PO once per day on days 1 to 21
28 Day Cycles
References
- 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