Difference between revisions of "Hepatocellular carcinoma"

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==Bevacizumab (Avastin)==
 
==Bevacizumab (Avastin)==
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
*[[Bevacizumab (Avastin)]] 5-10 mg/kg IV on day 1
 
*[[Bevacizumab (Avastin)]] 5-10 mg/kg IV on day 1
  
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# 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. [http://jco.ascopubs.org/content/26/18/2992.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18565886 PubMed]
 
# 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. [http://jco.ascopubs.org/content/26/18/2992.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18565886 PubMed]
  
−
==Bevacizumab (Avastin) & Capecitabine (Xeloda)==
+
==Bevacizumab & Capecitabine==
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
*[[Bevacizumab (Avastin)]] 7.5 mg/kg IV on day 1
 
*[[Bevacizumab (Avastin)]] 7.5 mg/kg IV on day 1
−
*[[Capecitabine (Xeloda)]] 800 mg/m2 PO BID on days 1-14
+
*[[Capecitabine (Xeloda)]] 800 mg/m2 PO BID on days 1 to 14
  
 
'''21-day cycles x 6 or more cycles depending on response'''
 
'''21-day cycles x 6 or more cycles depending on response'''
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# 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. [http://www.nature.com/bjc/journal/v102/n6/full/6605580a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20160718 PubMed]
 
# 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. [http://www.nature.com/bjc/journal/v102/n6/full/6605580a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20160718 PubMed]
  
−
==Bevacizumab (Avastin), Capecitabine (Xeloda), Oxaliplatin (Eloxatin)==
+
==Bevacizumab, Capecitabine, Oxaliplatin==
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
*[[Bevacizumab (Avastin)]] 5 mg/kg IV on day 1
 
*[[Bevacizumab (Avastin)]] 5 mg/kg IV on day 1
 
**Infusion times for bevacizumab are 75-105 minutes for the first dose, which if tolerated could be decreased to 50-70 minutes for the second dose, then 20-40 minutes for dose 3 and later  
 
**Infusion times for bevacizumab are 75-105 minutes for the first dose, which if tolerated could be decreased to 50-70 minutes for the second dose, then 20-40 minutes for dose 3 and later  
−
*[[Capecitabine (Xeloda)]] 825 mg/m2 PO BID on days 1-14
+
*[[Capecitabine (Xeloda)]] 825 mg/m2 PO BID on days 1 to 14
 
*[[Oxaliplatin (Eloxatin)]] 130 mg/m2 IV over 2 hours on day 1
 
*[[Oxaliplatin (Eloxatin)]] 130 mg/m2 IV over 2 hours on day 1
  
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# 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. doi: 10.1002/cncr.25889. Epub 2011 Jan 24. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.25889/abstract link to original article] '''contains verified regimen''' [http://www.ncbi.nlm.nih.gov/pubmed/21264839 PubMed]
 
# 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. doi: 10.1002/cncr.25889. Epub 2011 Jan 24. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.25889/abstract link to original article] '''contains verified regimen''' [http://www.ncbi.nlm.nih.gov/pubmed/21264839 PubMed]
  
−
==Bevacizumab (Avastin) & Erlotinib (Tarceva)==
+
==Bevacizumab & Erlotinib==
 
===Regimen===
 
===Regimen===
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV on days 1 & 15
+
Level of Evidence:
−
*[[Erlotinib (Tarceva)]] 150 mg PO on days 1-28
+
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
 +
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 +
*[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 28
  
 
'''28-day cycles'''
 
'''28-day cycles'''
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==Capecitabine (Xeloda)==
 
==Capecitabine (Xeloda)==
 
===Regimen===
 
===Regimen===
−
*[[Capecitabine (Xeloda)]] 1000 mg/m2 PO BID on days 1-14
+
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Randomized Phase II, >20 per arm</span>
 +
 
 +
*[[Capecitabine (Xeloda)]] 1000 mg/m2 PO BID on days 1 to 14
  
 
'''21-day cycles'''
 
'''21-day cycles'''
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===References===
 
===References===
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.20368/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15274071 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.20368/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15274071 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. doi: 10.1007/s12032-013-0655-z. Epub 2013 Jul 4. [http://www.ncbi.nlm.nih.gov/pubmed/23824645 PubMed]
  
−
==CapeOx (XELOX)==
+
==CapeOx, XELOX==
 
CapeOX: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin
 
CapeOX: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin
 
<br>XELOX: '''<u>XEL</u>'''oda, '''<u>OX</u>'''aliplatin
 
<br>XELOX: '''<u>XEL</u>'''oda, '''<u>OX</u>'''aliplatin
 
===Regimen===
 
===Regimen===
−
*[[Capecitabine (Xeloda)]] 1000 mg/m2 PO BID on days 1-14
+
Level of Evidence:
 +
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
 +
*[[Capecitabine (Xeloda)]] 1000 mg/m2 PO BID on days 1 to 14
 
*[[Oxaliplatin (Eloxatin)]] 130 mg/m2 IV over 2 hours on day 1
 
*[[Oxaliplatin (Eloxatin)]] 130 mg/m2 IV over 2 hours on day 1
  
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==Doxorubicin (Adriamycin)==
 
==Doxorubicin (Adriamycin)==
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[Doxorubicin (Adriamycin)]] 60 mg/m2 IV on day 1
 
*[[Doxorubicin (Adriamycin)]] 60 mg/m2 IV on day 1
  
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==Fluorouracil (5-FU) & Folinic acid (Leucovorin)==
 
==Fluorouracil (5-FU) & Folinic acid (Leucovorin)==
 
===Regimen===
 
===Regimen===
−
*[[Fluorouracil (5-FU)]] 370 mg/m2 IV on days 1-5
+
Level of Evidence:
−
*[[Folinic acid (Leucovorin)]] 200 mg/m2 IV on days 1-5
+
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
 +
*[[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'''
 
'''28-day cycles'''
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GEMOX: '''<u>GEM</u>'''citabine, '''<u>OX</u>'''aliplatin
 
GEMOX: '''<u>GEM</u>'''citabine, '''<u>OX</u>'''aliplatin
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV on day 1
 
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV on day 1
 
*[[Oxaliplatin (Eloxatin)]] 100 mg/m2 IV over 2 hours on day 2
 
*[[Oxaliplatin (Eloxatin)]] 100 mg/m2 IV over 2 hours on day 2
Line 97: Line 170:
  
 
===References===
 
===References===
−
# 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. doi: 10.1016/j.jhep.2012.09.006. Epub 2012 Sep 16. [http://www.sciencedirect.com/science/article/pii/S0168827812006952 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22989572 PubMed]
+
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.22532/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17330837 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. doi: 10.1016/j.jhep.2012.09.006. Epub 2012 Sep 16. [http://www.sciencedirect.com/science/article/pii/S0168827812006952 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22989572 PubMed]
 +
 
 +
==Nolatrexed==
 +
 
 +
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
 +
''This drug was inferior in a randomized clinical trial and does not appear to be in clinical development at this time.  Included for reference purposes only.''
 +
 
 +
===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. [http://jco.ascopubs.org/content/25/21/3069.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17634485 PubMed]
 +
 
 +
==Placebo==
 +
 
 +
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
 +
''No treatment. Included for reference purposes only.''
 +
 
 +
===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. [http://www.nejm.org/doi/full/10.1056/NEJMoa0708857 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18650514 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970285-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19095497 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 Jan 10. [Epub ahead of print] [http://www.sciencedirect.com/science/article/pii/S0959804911010318 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22240282 PubMed]
  
 
==Sorafenib (Nexavar)==
 
==Sorafenib (Nexavar)==
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[Sorafenib (Nexavar)]] 400 mg PO BID
 
*[[Sorafenib (Nexavar)]] 400 mg PO BID
−
**Dose/schedule changes of Sorafenib (Nexavar) due to toxicity include 400 mg PO daily, 400 mg PO every other day, 200 mg PO BID, 200 mg PO daily
+
**Dose/schedule changes of Sorafenib (Nexavar) 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'''
 
'''given until progression of disease or unacceptable toxicity'''
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# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970285-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19095497 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970285-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19095497 PubMed]
 
# 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. [http://theoncologist.alphamedpress.org/content/14/1/70.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19144684 PubMed]
 
# 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. [http://theoncologist.alphamedpress.org/content/14/1/70.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19144684 PubMed]
−
# 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 Jan 10. [Epub ahead of print] [http://www.sciencedirect.com/science/article/pii/S0959804911010318 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22240282 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 Jan 10. [Epub ahead of print] [http://www.sciencedirect.com/science/article/pii/S0959804911010318 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22240282 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. doi: 10.1007/s12032-013-0655-z. Epub 2013 Jul 4. [http://www.ncbi.nlm.nih.gov/pubmed/23824645 PubMed]
  
 
==Sunitinib (Sutent)==
 
==Sunitinib (Sutent)==
 
===Regimen===
 
===Regimen===
−
*[[Sunitinib (Sutent)]] 37.5 mg PO daily on days 1-28
+
Level of Evidence:
−
**Dose of Sunitinib (Sutent) can be reduced to 25 and 12.5 mg daily depending on toxicity
+
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
 +
*[[Sunitinib (Sutent)]] 37.5 mg PO once per day on days 1 to 28
 +
**Dose of Sunitinib (Sutent) can be reduced to 25 and 12.5 mg once per day depending on toxicity
  
 
'''42-day cycles'''
 
'''42-day cycles'''
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=Biliary tract cancer (cholangiocarcinoma/gallbladder)=
 
=Biliary tract cancer (cholangiocarcinoma/gallbladder)=
 +
 +
==Best supportive care==
 +
 +
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 +
''No antineoplastic treatment. Included for reference purposes only.''
 +
 +
===References===
 +
# Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T, Svensson C. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 1996 Aug;7(6):593-600. [http://annonc.oxfordjournals.org/content/7/6/593.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8879373 PubMed] content property of [http://hemonc.org HemOnc.org]
 +
 
==Capecitabine (Xeloda)==
 
==Capecitabine (Xeloda)==
 
===Regimen===
 
===Regimen===
−
*[[Capecitabine (Xeloda)]] 1000 mg/m2 PO BID on days 1-14
+
Level of Evidence:
 +
<span
 +
style="background:#ff0000;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Retrospective</span>
 +
 
 +
*[[Capecitabine (Xeloda)]] 1000 mg/m2 PO BID on days 1 to 14
  
 
'''21-day cycles'''
 
'''21-day cycles'''
Line 133: Line 283:
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.20368/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15274071 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.20368/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15274071 PubMed]
  
−
==Capecitabine (Xeloda) & Mitomycin (Mutamycin)==
+
==Capecitabine & Mitomycin==
 
===Regimen===
 
===Regimen===
−
*[[Capecitabine (Xeloda)]] 1000 mg/m2 PO BID on days 1-14
+
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Randomized Phase II, >20 per arm</span>
 +
 
 +
*[[Capecitabine (Xeloda)]] 1000 mg/m2 PO BID on days 1 to 14
 
*[[Mitomycin (Mutamycin)]] 8 mg/m2 IV bolus on day 1
 
*[[Mitomycin (Mutamycin)]] 8 mg/m2 IV bolus on day 1
  
Line 149: Line 307:
 
ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 
ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[Epirubicin (Ellence)]] 50 mg/m2 IV on day 1
 
*[[Epirubicin (Ellence)]] 50 mg/m2 IV on day 1
 
*[[Cisplatin (Platinol)]] 60 mg/m2 IV on day 1
 
*[[Cisplatin (Platinol)]] 60 mg/m2 IV on day 1
−
*[[Fluorouracil (5-FU)]] 200 mg/m2/day IV continuous infusion on days 1-21
+
*[[Fluorouracil (5-FU)]] 200 mg/m2/day IV continuous infusion on days 1 to 21
  
 
'''21-day cycles'''
 
'''21-day cycles'''
Line 158: Line 324:
 
# Rao S, Cunningham D, Hawkins RE, Hill ME, Smith D, Daniel F, Ross PJ, Oates J, Norman AR. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer. Br J Cancer. 2005 May 9;92(9):1650-4. [http://www.nature.com/bjc/journal/v92/n9/full/6602576a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15856037 PubMed]
 
# Rao S, Cunningham D, Hawkins RE, Hill ME, Smith D, Daniel F, Ross PJ, Oates J, Norman AR. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer. Br J Cancer. 2005 May 9;92(9):1650-4. [http://www.nature.com/bjc/journal/v92/n9/full/6602576a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15856037 PubMed]
  
−
==Fluorouracil (5-FU) & Folinic acid (Leucovorin)==
+
==FELV, FELv==
−
===Regimen===
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m2 IV bolus on days 1-2, given first
 
−
*[[Folinic acid (Leucovorin)]] 60 mg/m2 IV bolus on days 1-2, given second, 40 minutes after Fluorouracil (5-FU)
 
−
 
 
−
'''14-day cycles'''
 
−
 
 
−
===References===
 
−
# Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T, Svensson C. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 1996 Aug;7(6):593-600. [http://annonc.oxfordjournals.org/content/7/6/593.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8879373 PubMed]
 
−
 
 
−
==Fluorouracil (5-FU), Folinic acid (Leucovorin), Etoposide (Vepesid) (FELV)==
 
 
FELV: '''<u>F</u>'''luorouracil , '''<u>E</u>'''toposide, '''<u>L</u>'''euco'''<u>V</u>'''orin
 
FELV: '''<u>F</u>'''luorouracil , '''<u>E</u>'''toposide, '''<u>L</u>'''euco'''<u>V</u>'''orin
 
===Regimen #1, Rao, et al. 2005===
 
===Regimen #1, Rao, et al. 2005===
−
*[[Fluorouracil (5-FU)]] 600 mg/m2 IV bolus on days 1-3, given first
+
Level of Evidence:
−
*[[Folinic acid (Leucovorin)]] 60 mg/m2 IV bolus on days 1-3, given last
+
<span
−
*[[Etoposide (Vepesid)]] 120 mg/m2 IV over 40 minutes on days 1-3, given second
+
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
 +
*[[Fluorouracil (5-FU)]] 600 mg/m2 IV bolus once per day on days 1 to 3, given first
 +
*[[Folinic acid (Leucovorin)]] 60 mg/m2 IV bolus once per day on days 1 to 3, given last
 +
*[[Etoposide (Vepesid)]] 120 mg/m2 IV over 40 minutes once per day on days 1 to 3, given second
  
 
'''21-day cycles'''
 
'''21-day cycles'''
  
 
===Regimen #2, Glimelius, et al. 1996===
 
===Regimen #2, Glimelius, et al. 1996===
−
*[[Fluorouracil (5-FU)]] 500 mg/m2 IV bolus on days 1-3, given first
+
*[[Fluorouracil (5-FU)]] 500 mg/m2 IV bolus once per day on days 1 to 3, given first
−
*[[Folinic acid (Leucovorin)]] 60 mg/m2 IV bolus on days 1-3, given last
+
*[[Folinic acid (Leucovorin)]] 60 mg/m2 IV bolus once per day on days 1 to 3, given last
−
*[[Etoposide (Vepesid)]] 120 mg/m2 IV over 40 minutes on days 1-3, given second
+
*[[Etoposide (Vepesid)]] 120 mg/m2 IV over 40 minutes once per day on days 1 to 3, given second
  
 
'''21-day cycles'''
 
'''21-day cycles'''
Line 188: Line 352:
 
# Rao S, Cunningham D, Hawkins RE, Hill ME, Smith D, Daniel F, Ross PJ, Oates J, Norman AR. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer. Br J Cancer. 2005 May 9;92(9):1650-4. [http://www.nature.com/bjc/journal/v92/n9/full/6602576a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15856037 PubMed]
 
# Rao S, Cunningham D, Hawkins RE, Hill ME, Smith D, Daniel F, Ross PJ, Oates J, Norman AR. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer. Br J Cancer. 2005 May 9;92(9):1650-4. [http://www.nature.com/bjc/journal/v92/n9/full/6602576a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15856037 PubMed]
  
−
==Fluorouracil (5-FU), Folinic acid (Leucovorin), Gemcitabine (Gemzar)==
+
==Fluorouracil (5-FU) & Folinic acid (Leucovorin)==
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 +
*[[Fluorouracil (5-FU)]] 500 mg/m2 IV bolus once per day on days 1 & 2, given first
 +
*[[Folinic acid (Leucovorin)]] 60 mg/m2 IV bolus once per day on days 1 & 2, given second, 40 minutes after Fluorouracil (5-FU)
 +
 +
'''14-day cycles'''
 +
 +
===References===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 +
# Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T, Svensson C. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 1996 Aug;7(6):593-600. [http://annonc.oxfordjournals.org/content/7/6/593.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8879373 PubMed]
 +
 +
 +
==Fluorouracil (5-FU), Folinic acid, Gemcitabine==
 +
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Randomized Phase II, <20 per arm</span>
 +
 
*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus, then 600 mg/m2 IV continuous infusion over 22 hours on day 1
 
*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus, then 600 mg/m2 IV continuous infusion over 22 hours on day 1
 
*[[Folinic acid (Leucovorin)]] 100 mg/m2 IV over 2 hours on day 1
 
*[[Folinic acid (Leucovorin)]] 100 mg/m2 IV over 2 hours on day 1
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV on days 1 & 8
+
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1 & 8
  
 
'''21-day cycles'''
 
'''21-day cycles'''
Line 201: Line 400:
 
==Gemcitabine (Gemzar)==
 
==Gemcitabine (Gemzar)==
 
===Regimen #1, Valle, et al. 2010===
 
===Regimen #1, Valle, et al. 2010===
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 minutes on days 1, 8, 15
+
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
  
 
'''28-day cycles x 3-6 cycles depending on response'''
 
'''28-day cycles x 3-6 cycles depending on response'''
  
 
===Regimen #2, Gebbia, et al. 2001===
 
===Regimen #2, Gebbia, et al. 2001===
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 minutes on days 1, 8, 15
+
Level of Evidence:
 +
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Randomized Phase II, <20 per arm</span>
 +
 
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
  
 
'''30-day cycles'''
 
'''30-day cycles'''
Line 214: Line 429:
 
# Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. [http://www.nejm.org/doi/full/10.1056/NEJMoa0908721 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20375404 PubMed]
 
# Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. [http://www.nejm.org/doi/full/10.1056/NEJMoa0908721 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20375404 PubMed]
  
−
==Gemcitabine (Gemzar) & Cisplatin (Platinol)==
+
==Gemcitabine & Cisplatin==
 
===Regimen===
 
===Regimen===
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 minutes on days 1 & 8, given second
+
Level of Evidence:
−
*[[Cisplatin (Platinol)]] 25 mg/m2 IV over 1 hour on days 1 & 8, given first
+
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
  
−
'''21-day cycles x 4-8 cycles depending on response'''
+
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
 +
*[[Cisplatin (Platinol)]] 25 mg/m2 IV over 1 hour once per day on days 1 & 8, given first
 +
 
 +
'''21-day cycles x 4 to 8 cycles depending on response'''
  
 
Supportive medications:
 
Supportive medications:
Line 228: Line 451:
 
# Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. [http://www.nejm.org/doi/full/10.1056/NEJMoa0908721 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20375404 PubMed]
 
# Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. [http://www.nejm.org/doi/full/10.1056/NEJMoa0908721 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20375404 PubMed]
  
−
==Gemcitabine (Gemzar) & Mitomycin (Mutamycin)==
+
==Gemcitabine & Mitomycin==
 
===Regimen===
 
===Regimen===
−
*[[Gemcitabine (Gemzar)]] 2000 mg/m2 IV over 30 minutes on days 1 & 15
+
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Randomized Phase II, >20 per arm</span>
 +
 
 +
*[[Gemcitabine (Gemzar)]] 2000 mg/m2 IV over 30 minutes once per day on days 1 & 15
 
*[[Mitomycin (Mutamycin)]] 8 mg/m2 IV bolus on day 1
 
*[[Mitomycin (Mutamycin)]] 8 mg/m2 IV bolus on day 1
  
Line 244: Line 475:
 
GEMOX-B: '''<u>GEM</u>'''citabine, '''<u>OX</u>'''aliplatin, '''<u>B</u>'''evacizumab
 
GEMOX-B: '''<u>GEM</u>'''citabine, '''<u>OX</u>'''aliplatin, '''<u>B</u>'''evacizumab
 
===Regimen===
 
===Regimen===
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 100 minutes on days 1 & 15, given second
+
Level of Evidence:
−
*[[Oxaliplatin (Eloxatin)]] 85 mg/m2 IV over 2 hours on days 1 & 15, given last
+
<span
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV on days 1 & 15, given first
+
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 100 minutes once per day on days 1 & 15, given second
 +
*[[Oxaliplatin (Eloxatin)]] 85 mg/m2 IV over 2 hours once per day on days 1 & 15, given last
 +
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15, given first
  
 
'''28-day cycles'''
 
'''28-day cycles'''

Revision as of 23:48, 14 July 2013

Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer.

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.


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.

Hepatocellular carcinoma

Bevacizumab (Avastin)

Regimen

Level of Evidence: Phase II

14-day cycles

References

  1. 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 PubMed

Bevacizumab & Capecitabine

Regimen

Level of Evidence: Phase II

21-day cycles x 6 or more cycles depending on response

References

  1. 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 PubMed

Bevacizumab, Capecitabine, Oxaliplatin

Regimen

Level of Evidence: Phase II

  • Bevacizumab (Avastin) 5 mg/kg IV on day 1
    • Infusion times for bevacizumab are 75-105 minutes for the first dose, which if tolerated could be decreased to 50-70 minutes for the second dose, then 20-40 minutes for dose 3 and later
  • Capecitabine (Xeloda) 825 mg/m2 PO BID on days 1 to 14
  • Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours on day 1

21-day cycles

References

  1. 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. doi: 10.1002/cncr.25889. Epub 2011 Jan 24. link to original article contains verified regimen PubMed

Bevacizumab & Erlotinib

Regimen

Level of Evidence: Phase II

28-day cycles

References

  1. 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

Capecitabine (Xeloda)

Regimen

Level of Evidence: Randomized Phase II, >20 per arm

21-day cycles

References

  1. 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 contains verified protocol PubMed
  2. 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. doi: 10.1007/s12032-013-0655-z. Epub 2013 Jul 4. PubMed

CapeOx, XELOX

CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda, OXaliplatin

Regimen

Level of Evidence: Phase II

21-day cycles

References

  1. 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 PubMed

Doxorubicin (Adriamycin)

Regimen

Level of Evidence: Phase III

21-day cycles

References

  1. 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

Fluorouracil (5-FU) & Folinic acid (Leucovorin)

Regimen

Level of Evidence: Phase II

28-day cycles

References

  1. 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. PubMed

GEMOX

GEMOX: GEMcitabine, OXaliplatin

Regimen

Level of Evidence: Phase II

14-day cycles, given until progression of disease, unacceptable toxicity, or patient choice

References

  1. 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
  2. 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. doi: 10.1016/j.jhep.2012.09.006. Epub 2012 Sep 16. link to original article contains verified protocol PubMed

Nolatrexed

Regimen

Level of Evidence: Phase III

This drug was inferior in a randomized clinical trial and does not appear to be in clinical development at this time. Included for reference purposes only.

References

  1. 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

Placebo

Regimen

Level of Evidence: Phase III

No treatment. Included for reference purposes only.

References

  1. 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
  2. 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
  3. 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 Jan 10. [Epub ahead of print] link to original article contains verified protocol PubMed

Sorafenib (Nexavar)

Regimen

Level of Evidence: Phase III

  • Sorafenib (Nexavar) 400 mg PO BID
    • Dose/schedule changes of Sorafenib (Nexavar) 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

  1. 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
  2. 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
  3. 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
  4. 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 contains verified protocol PubMed
  5. 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 Jan 10. [Epub ahead of print] link to original article contains verified protocol PubMed
  6. 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. doi: 10.1007/s12032-013-0655-z. Epub 2013 Jul 4. PubMed

Sunitinib (Sutent)

Regimen

Level of Evidence: Phase II

  • Sunitinib (Sutent) 37.5 mg PO once per day on days 1 to 28
    • Dose of Sunitinib (Sutent) can be reduced to 25 and 12.5 mg once per day depending on toxicity

42-day cycles

References

  1. 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 PubMed

Biliary tract cancer (cholangiocarcinoma/gallbladder)

Best supportive care

Regimen

Level of Evidence: Phase III

No antineoplastic treatment. Included for reference purposes only.

References

  1. Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T, Svensson C. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 1996 Aug;7(6):593-600. link to original article contains verified protocol PubMed content property of HemOnc.org

Capecitabine (Xeloda)

Regimen

Level of Evidence: Retrospective

21-day cycles

References

  1. 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 contains verified protocol PubMed

Capecitabine & Mitomycin

Regimen

Level of Evidence: Randomized Phase II, >20 per arm

28-day cycles

Supportive medications:

References

  1. Kornek GV, Schuell B, Laengle F, Gruenberger T, Penz M, Karall K, Depisch D, Lang F, Scheithauer W. Mitomycin C in combination with capecitabine or biweekly high-dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial. Ann Oncol. 2004 Mar;15(3):478-83. link to original article contains verified protocol PubMed

ECF

ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Level of Evidence: Phase III

21-day cycles

References

  1. Rao S, Cunningham D, Hawkins RE, Hill ME, Smith D, Daniel F, Ross PJ, Oates J, Norman AR. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer. Br J Cancer. 2005 May 9;92(9):1650-4. link to original article contains verified protocol PubMed

FELV, FELv

FELV: Fluorouracil , Etoposide, LeucoVorin

Regimen #1, Rao, et al. 2005

Level of Evidence: Phase III

21-day cycles

Regimen #2, Glimelius, et al. 1996

21-day cycles

References

  1. Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T, Svensson C. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 1996 Aug;7(6):593-600. link to original article contains verified protocol PubMed content property of HemOnc.org
  2. Rao S, Cunningham D, Hawkins RE, Hill ME, Smith D, Daniel F, Ross PJ, Oates J, Norman AR. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer. Br J Cancer. 2005 May 9;92(9):1650-4. link to original article contains verified protocol PubMed

Fluorouracil (5-FU) & Folinic acid (Leucovorin)

Regimen

Level of Evidence: Phase III

14-day cycles

References

Level of Evidence: Phase III

  1. Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T, Svensson C. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 1996 Aug;7(6):593-600. link to original article contains verified protocol PubMed


Fluorouracil (5-FU), Folinic acid, Gemcitabine

Regimen

Level of Evidence: Randomized Phase II, <20 per arm

21-day cycles

References

  1. Gebbia V, Giuliani F, Maiello E, Colucci G, Verderame F, Borsellino N, Mauceri G, Caruso M, Tirrito ML, Valdesi M. Treatment of inoperable and/or metastatic biliary tree carcinomas with single-agent gemcitabine or in combination with levofolinic acid and infusional fluorouracil: results of a multicenter phase II study. J Clin Oncol. 2001 Oct 15;19(20):4089-91. link to original article contains verified protocol PubMed

Gemcitabine (Gemzar)

Regimen #1, Valle, et al. 2010

Level of Evidence: Phase III

28-day cycles x 3-6 cycles depending on response

Regimen #2, Gebbia, et al. 2001

Level of Evidence: Randomized Phase II, <20 per arm

30-day cycles

References

  1. Gebbia V, Giuliani F, Maiello E, Colucci G, Verderame F, Borsellino N, Mauceri G, Caruso M, Tirrito ML, Valdesi M. Treatment of inoperable and/or metastatic biliary tree carcinomas with single-agent gemcitabine or in combination with levofolinic acid and infusional fluorouracil: results of a multicenter phase II study. J Clin Oncol. 2001 Oct 15;19(20):4089-91. link to original article contains verified protocol PubMed
  2. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. link to original article contains verified protocol PubMed

Gemcitabine & Cisplatin

Regimen

Level of Evidence: Phase III

21-day cycles x 4 to 8 cycles depending on response

Supportive medications:

  • Cisplatin is mixed in a solution of 1 liter of normal saline with 20 mmol potassium chloride, 8 mmol magnesium sulfate
  • After cisplatin, 500 mL normal saline given over 30 minutes

References

  1. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. link to original article contains verified protocol PubMed

Gemcitabine & Mitomycin

Regimen

Level of Evidence: Randomized Phase II, >20 per arm

28-day cycles

Supportive medications:

References

  1. Kornek GV, Schuell B, Laengle F, Gruenberger T, Penz M, Karall K, Depisch D, Lang F, Scheithauer W. Mitomycin C in combination with capecitabine or biweekly high-dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial. Ann Oncol. 2004 Mar;15(3):478-83. link to original article contains verified protocol PubMed

GEMOX-B

GEMOX-B: GEMcitabine, OXaliplatin, Bevacizumab

Regimen

Level of Evidence: Phase II

28-day cycles

References

  1. Zhu AX, Meyerhardt JA, Blaszkowsky LS, Kambadakone AR, Muzikansky A, Zheng H, Clark JW, Abrams TA, Chan JA, Enzinger PC, Bhargava P, Kwak EL, Allen JN, Jain SR, Stuart K, Horgan K, Sheehan S, Fuchs CS, Ryan DP, Sahani DV. 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. 2010 Jan;11(1):48-54. Epub 2009 Nov 20. link to original article contains verified protocol PubMed
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