Difference between revisions of "Hepatocellular carcinoma"
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|[http://www.nejm.org/doi/full/10.1056/NEJMoa0908721 Valle et al. 2010 (ABC-02)] | |[http://www.nejm.org/doi/full/10.1056/NEJMoa0908721 Valle et al. 2010 (ABC-02)] | ||
|style="background-color:#00CD00"|Phase III | |style="background-color:#00CD00"|Phase III | ||
− | |[[Hepatobiliary_cancer# | + | |[[Hepatobiliary_cancer#Gemcitabine_monotherapy|Gemcitabine]] |
|style="background-color:#00CD00"|Superior OS | |style="background-color:#00CD00"|Superior OS | ||
|- | |- |
Revision as of 02:29, 19 August 2017
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38 regimens on this page
48 variants on this page
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Liver cancer or hepatobiliary cancer comprises cancers that arise within the liver and its hepatocytes (hepatocellular carcinoma) and the biliary tract cancers, which include bile duct cancer/cholangiocarcinoma and gallbladder cancer.
Guidelines
ESMO
- Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
- Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
NCCN
Hepatocellular carcinoma
Bevacizumab (Avastin)
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Regimen
Study | Evidence |
Siegel et al. 2008 | Phase II |
The dose here was a pre-planned escalation dose.
Chemotherapy
- Bevacizumab (Avastin) 10 mg/kg IV once on day 1
14-day cycles
References
- Siegel AB, Cohen EI, Ocean A, Lehrer D, Goldenberg A, Knox JJ, Chen H, Clark-Garvey S, Weinberg A, Mandeli J, Christos P, Mazumdar M, Popa E, Brown RS Jr, Rafii S, Schwartz JD. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol. 2008 Jun 20;26(18):2992-8. link to original article contains verified protocol link to PMC article PubMed
Bevacizumab & Capecitabine
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Regimen
Study | Evidence |
Hsu et al. 2010 | Phase II |
Chemotherapy
- Bevacizumab (Avastin) 7.5 mg/kg IV once on day 1
- Capecitabine (Xeloda) 800 mg/m2 PO BID on days 1 to 14
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
Bevacizumab, Capecitabine, Oxaliplatin
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Regimen
Study | Evidence |
Sun et al. 2011 | Phase II |
Chemotherapy
- 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
- 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
21-day cycles
References
- Sun W, Sohal D, Haller DG, Mykulowycz K, Rosen M, Soulen MC, Caparro M, Teitelbaum UR, Giantonio B, O'Dwyer PJ, Shaked A, Reddy R, Olthoff K. Phase 2 trial of bevacizumab, capecitabine, and oxaliplatin in treatment of advanced hepatocellular carcinoma. Cancer. 2011 Jul 15;117(14):3187-92. Epub 2011 Jan 24. link to original article contains verified regimen PubMed
Bevacizumab & Erlotinib
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Regimen
Study | Evidence |
Thomas et al. 2009 | Phase II |
Chemotherapy
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
- Erlotinib (Tarceva) 150 mg PO once per day
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
Capecitabine (Xeloda)
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Regimen
Study | Evidence | Comparator | Efficacy |
Abdel-Rahman et al. 2013 | Randomized Phase II | Sorafenib | Inferior OS |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
21-day cycles
References
- Retrospective: Patt YZ, Hassan MM, Aguayo A, Nooka AK, Lozano RD, Curley SA, Vauthey JN, Ellis LM, Schnirer II, Wolff RA, Charnsangavej C, Brown TD. Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma. Cancer. 2004 Aug 1;101(3):578-86. link to original article PubMed
- Abdel-Rahman O, Abdel-Wahab M, Shaker M, Abdel-Wahab S, Elbassiony M, Ellithy M. Sorafenib versus capecitabine in the management of advanced hepatocellular carcinoma. Med Oncol. 2013 Sep;30(3):655. Epub 2013 Jul 4. link to original article PubMed
CapeOx; XELOX
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CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda (Capecitabine), OXaliplatin
Regimen
Study | Evidence |
Boige et al. 2007 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
21-day cycles
References
- Boige V, Raoul JL, Pignon JP, Bouché O, Blanc JF, Dahan L, Jouve JL, Dupouy N, Ducreux M; Fédération Francophone de Cancérologie Digestive. Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial. Br J Cancer. 2007 Oct 8;97(7):862-7. Epub 2007 Sep 18. link to original article contains verified protocol link to PMC article PubMed
Doxorubicin (Adriamycin)
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Regimen
Study | Evidence | Comparator | Efficacy |
Gish et al. 2007 | Phase III | Nolatrexed | Superior OS |
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
21-day cycles
References
- Gish RG, Porta C, Lazar L, Ruff P, Feld R, Croitoru A, Feun L, Jeziorski K, Leighton J, Gallo J, Kennealey GT. Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin. J Clin Oncol. 2007 Jul 20;25(21):3069-75. link to original article contains verified protocol PubMed
Fluorouracil & Folinic acid
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Regimen
Study | Evidence |
Porta et al. 1995 | Phase II |
Chemotherapy
- Fluorouracil (5-FU) 370 mg/m2 IV once per day on days 1 to 5
- Folinic acid (Leucovorin) 200 mg/m2 IV once per day on days 1 to 5
28-day cycles
References
- Porta C, Moroni M, Nastasi G, Arcangeli G. 5-Fluorouracil and d,l-leucovorin calcium are active to treat unresectable hepatocellular carcinoma patients: preliminary results of a phase II study. Oncology. 1995 Nov-Dec;52(6):487-91. link to original article PubMed
GEMOX
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GEMOX: GEMcitabine, OXaliplatin
Regimen
Study | Evidence |
Louafi et al. 2007 | Phase II |
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
Placebo
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Regimen
Study | Evidence | Comparator | Efficacy |
Llovet et al. 2008 (SHARP) | Phase III | Sorafenib | Inferior OS |
Cheng et al. 2008 | Phase III | Sorafenib | Seems to have inferior OS |
Zhu et al. 2015 (REACH) | Phase III | Ramucirumab | Seems not superior |
Bruix et al. 2016 (RESORCE) | Phase III | Regorafenib | Inferior OS |
No active antineoplastic treatment.
References
- Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. link to original article contains verified protocol PubMed
- Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. Epub 2008 Dec 16. link to original article contains verified protocol PubMed
- Subset analysis: Cheng AL, Guan Z, Chen Z, Tsao CJ, Qin S, Kim JS, Yang TS, Tak WY, Pan H, Yu S, Xu J, Fang F, Zou J, Lentini G, Voliotis D, Kang YK. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: Subset analyses of the phase III Sorafenib Asia-Pacific trial. Eur J Cancer. 2012 Jul;48(10):1452-65. Epub 2012 Jan 10. link to original article contains verified protocol PubMed
- Zhu AX, Park JO, Ryoo BY, Yen CJ, Poon R, Pastorelli D, Blanc JF, Chung HC, Baron AD, Pfiffer TE, Okusaka T, Kubackova K, Trojan J, Sastre J, Chau I, Chang SC, Abada PB, Yang L, Schwartz JD, Kudo M; REACH Trial Investigators. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2015 Jul;16(7):859-70. Epub 2015 Jun 18. link to original article PubMed
- Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, Gerolami R, Masi G, Ross PJ, Song T, Bronowicki JP, Ollivier-Hourmand I, Kudo M, Cheng AL, Llovet JM, Finn RS, LeBerre MA, Baumhauer A, Meinhardt G, Han G; RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Jan 7;389(10064):56-66. Epub 2016 Dec 6. Erratum in: Lancet. 2017 Jan 7;389(10064):36. link to original article contains protocol PubMed
Regorafenib (Stivarga)
Regorafenib (Stivarga) for hepatocellular carcinoma
Sorafenib (Nexavar)
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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 |
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
Sunitinib (Sutent)
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Regimen
Study | Evidence |
Zhu et al. 2009 | Phase II |
Chemotherapy
- Sunitinib (Sutent) 37.5 mg PO once per day on days 1 to 28
- Dose can be reduced to 25 and 12.5 mg once per day depending on toxicity
42-day cycles
References
- Zhu AX, Sahani DV, Duda DG, di Tomaso E, Ancukiewicz M, Catalano OA, Sindhwani V, Blaszkowsky LS, Yoon SS, Lahdenranta J, Bhargava P, Meyerhardt J, Clark JW, Kwak EL, Hezel AF, Miksad R, Abrams TA, Enzinger PC, Fuchs CS, Ryan DP, Jain RK. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol. 2009 Jun 20;27(18):3027-35. Epub 2009 May 26. link to original article contains verified protocol link to PMC article PubMed
TACE -> 5-FU
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TACE: Trans-Arterial ChemoEmbolization
Regimen
Study | Evidence | Comparator | Efficacy |
Kawata et al. 2001 | Phase III | TACE -> 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
Biliary tract cancer (cholangiocarcinoma/gallbladder)
Best supportive care
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Regimen
Study | Evidence | Comparator | Efficacy |
Glimelius et al. 1996 | Phase III | FELv | Inferior OS |
Fluorouracil & Folinic acid | Inferior OS |
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. link to original article contains verified protocol PubMed content property of HemOnc.org
Bevacizumab & Erlotinib
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Regimen
Study | Evidence |
Lubner et al. 2010 | Phase II |
Chemotherapy
- Bevacizumab (Avastin) 5 mg/kg IV once per day on days 1 & 15
- Erlotinib (Tarceva) 150 mg PO once per day
28-day cycles, given until progression of disease or unacceptable toxicity
References
- Lubner SJ, Mahoney MR, Kolesar JL, Loconte NK, Kim GP, Pitot HC, Philip PA, Picus J, Yong WP, Horvath L, Van Hazel G, Erlichman CE, Holen KD. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II Consortium study. J Clin Oncol. 2010 Jul 20;28(21):3491-7. Epub 2010 Jun 7. link to original article contains verified protocol link to PMC article PubMed
Capecitabine (Xeloda)
back to top |
Regimen
Study | Evidence |
Patt et al. 2004 | Retrospective |
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
Capecitabine & Mitomycin
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Regimen
Study | Evidence | Comparator | Efficacy |
Kornek et al. 2004 | Randomized Phase II | Gemcitabine & Mitomycin | Might have superior ORR |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
- Mitomycin (Mutamycin) 8 mg/m2 IV bolus once on day 1
Supportive medications
- Dexamethasone (Decadron) and 5-HT3 antagonists on the day of IV chemotherapy
28-day cycles
References
- 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
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ECF: Epirubicin, Cisplatin, Fluorouracil
Regimen
Study | Evidence | Comparator | Efficacy |
Rao et al. 2005 | Phase III | FELV | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion on days 1 to 21
21-day cycles
References
- 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 link to PMC article PubMed
FELV
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FELV: Fluorouracil , Etoposide, LeucoVorin (Folinic acid)
Regimen #1
Study | Evidence | Comparator | Efficacy |
Rao et al. 2005 | Phase III | ECF | Seems not superior |
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV bolus once per day on days 1 to 3, given first
- Etoposide (Vepesid) 120 mg/m2 IV over 40 minutes once per day on days 1 to 3, given second
- Folinic acid (Leucovorin) 60 mg/m2 IV bolus once per day on days 1 to 3, given last
21-day cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
Glimelius et al. 1996 | Phase III | Best supportive care | Superior OS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV bolus once per day on days 1 to 3, given first
- Etoposide (Vepesid) 120 mg/m2 IV over 40 minutes once per day on days 1 to 3, given second
- Folinic acid (Leucovorin) 60 mg/m2 IV bolus once per day on days 1 to 3, given last
21-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. link to original article contains verified protocol PubMed content property of HemOnc.org
- 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 link to PMC article PubMed
Fluorouracil & Folinic acid
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
Glimelius et al. 1996 | Phase III | Best supportive care | Superior OS |
Chemotherapy
- 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
- 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, Folinic acid, Gemcitabine
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Regimen
Study | Evidence |
Gebbia et al. 2001 | Phase II |
Chemotherapy
- 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 once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- 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 monotherapy
back to top |
Regimen #1
Study | Evidence | Comparator | Efficacy |
Valle et al. 2010 (ABC-02) | Phase III | Gemcitabine & Cisplatin | Inferior OS |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 3 to 6 cycles depending on response
Regimen #2
Study | Evidence |
Gebbia et al. 2001 | Phase II |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
30-day cycles
References
- 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
- 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
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Regimen
Study | Evidence | Comparator | Efficacy |
Valle et al. 2010 (ABC-02) | Phase III | Gemcitabine | Superior OS |
Chemotherapy
- 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
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
21-day cycle for 4 to 8 cycles depending on response
References
- 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
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
Kornek et al. 2004 | Randomized Phase II | Capecitabine & Mitomycin | Might have inferior ORR |
Chemotherapy
- Gemcitabine (Gemzar) 2000 mg/m2 IV over 30 minutes once per day on days 1 & 15
- Mitomycin (Mutamycin) 8 mg/m2 IV bolus once on day 1
Supportive medications
- Dexamethasone (Decadron) and 5-HT3 antagonists on the day of IV chemotherapy
28-day cycles
References
- 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
Gemcitabine & Oxaliplatin
Gemcitabine & Oxaliplatin for biliary tract cancer
GEMOX-B
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GEMOX-B: GEMcitabine, OXaliplatin, Bevacizumab
Regimen
Study | Evidence |
Zhu et al. 2009 | Phase II |
Chemotherapy
- 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
References
- 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
Periampullary adenocarcinoma
Placebo
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Regimen
Study | Evidence | Comparator | Efficacy |
Neoptolemos et al. 2012 (ESPAC-3 ) | Phase III | 5-FU & Leucovorin Gemcitabine |
Seems not superior |
No active antineoplastic treatment after surgery.
References
- Neoptolemos JP, Moore MJ, Cox TF, Valle JW, Palmer DH, McDonald AC, Carter R, Tebbutt NC, Dervenis C, Smith D, Glimelius B, Charnley RM, Lacaine F, Scarfe AG, Middleton MR, Anthoney A, Ghaneh P, Halloran CM, Lerch MM, Oláh A, Rawcliffe CL, Verbeke CS, Campbell F, Büchler MW; European Study Group for Pancreatic Cancer. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012 Jul 11;308(2):147-56. Erratum in: JAMA. 2012 Nov 14;308(18):1861. link to original article PubMed