Difference between revisions of "Cholangiocarcinoma"
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− | ==== | + | ====Targeted therapy==== |
*[[Erlotinib (Tarceva)]] 150 mg PO once per day | *[[Erlotinib (Tarceva)]] 150 mg PO once per day | ||
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*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 100 minutes once per day on days 1 & 15, '''given second''' | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 100 minutes once per day on days 1 & 15, '''given second''' | ||
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 15, '''given third''' | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 15, '''given third''' | ||
+ | ====Targeted therapy==== | ||
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15, '''given first''' | *[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15, '''given first''' | ||
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''Note: Patients with unresectable or metastatic disease with IDH1 mutation with progression after at least one prior systemic therapy.'' | ''Note: Patients with unresectable or metastatic disease with IDH1 mutation with progression after at least one prior systemic therapy.'' | ||
− | ==== | + | ====Targeted therapy==== |
*[[Ivosidenib (Tibsovo)]] 500 mg PO once per day | *[[Ivosidenib (Tibsovo)]] 500 mg PO once per day | ||
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====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*Fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement | *Fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement | ||
− | ==== | + | ====Targeted therapy==== |
*[[Pemigatinib (Pemazyre)]] 13.5 mg PO once per day on days 1 to 14 | *[[Pemigatinib (Pemazyre)]] 13.5 mg PO once per day on days 1 to 14 | ||
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''Only studied in patients with advanced biliary cancer who failed at least 1 line of systemic therapy.'' | ''Only studied in patients with advanced biliary cancer who failed at least 1 line of systemic therapy.'' | ||
− | ==== | + | ====Targeted therapy==== |
*[[Regorafenib (Stivarga)]] 120 mg PO once per day on days 1 to 21 | *[[Regorafenib (Stivarga)]] 120 mg PO once per day on days 1 to 21 |
Revision as of 20:36, 22 July 2020
Page editor | Section editor | ||
---|---|---|---|
Ari Seifter, MD University of Illinois at Chicago Chicago, IL |
Neeta K. Venepalli, MD, MBA University of Illinois at Chicago Chicago, IL |
29 regimens on this page
35 variants on this page
|
Note: there is some overlap, especially in the earlier literature, between treatment regimens for cholangiocarcinoma and those for pancreatic adenocarcinoma, periampullary adenocarcinoma, and gallbladder cancer; please see those pages for additional regimens.
Guidelines
ASCO
- 2019: Shroff et al. Adjuvant therapy for resected biliary tract cancer: ASCO Clinical Practice Guideline
ESMO
- 2016: Valle et al. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
NCCN
Adjuvant therapy
Capecitabine monotherapy
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Primrose et al. 2019 (BILCAP) | 2006-2014 | Phase III (E-esc) | Observation | Might have superior OS |
Preceding treatment
- Surgical resection with macroscopically curative resection
- Chemotherapy start date 8-16 weeks after surgery
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for 8 cycles
References
- BILCAP: Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D, Anthony A, Corrie P, Falk S, Finch-Jones M, Wasan H, Ross P, Wall L, Wadsley J, Evans JTR, Stocken D, Praseedom R, Ma YT, Davidson B, Neoptolemos JP, Iveson T, Raftery J, Zhu S, Cunningham D, Garden OJ, Stubbs C, Valle JW, Bridgewater J; BILCAP study group. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019 May;20(5):663-673. Epub 2019 Mar 25. Erratum in: Lancet Oncol. 2019 Apr 2. link to original article PubMed EudraCT 2005-003318-13
Capecitabine & Gemcitabine
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GemCap: Gemcitabine & Capecitabine
Regimen
Study | Evidence |
---|---|
Ben-Josef et al. 2015 (SWOG S0809) | Phase II |
Preceding treatment
Chemotherapy
- Capecitabine (Xeloda) 750 mg/m2/day PO twice per day on days 1 to 14
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
Subsequent treatment
- Capecitabine & RT
References
- SWOG S0809: Ben-Josef E, Guthrie KA, El-Khoueiry AB, Corless CL, Zalupski MM, Lowy AM, Thomas CR Jr, Alberts SR, Dawson LA, Micetich KC, Thomas MB, Siegel AB, Blanke CD. SWOG S0809: A phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol. 2015 Aug 20;33(24):2617-22. Epub 2015 May 11. link to original article link to PMC article contains verified protocol PubMed
Gemcitabine monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ebata et al. 2018 (BCAT) | 2007-2011 | Phase III (E-esc) | Observation | Did not meet primary endpoint of OS |
Preceding treatment
- Surgical resection with macroscopically curative resection
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycle for 6 cycles
References
- BCAT: Ebata T, Hirano S, Konishi M, Uesaka K, Tsuchiya Y, Ohtsuka M, Kaneoka Y, Yamamoto M, Ambo Y, Shimizu Y, Ozawa F, Fukutomi A, Ando M, Nimura Y, Nagino M; Bile Duct Cancer Adjuvant Trial (BCAT) Study Group. Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer. Br J Surg. 2018 Feb;105(3):192-202. link to original article PubMed UMIN 000000820
Gemcitabine/Fluorouracil & RT
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Gemcitabine/Fluorouracil & RT: Gemcitabine alternating with Fluorouracil & Radiation Therapy
Protocol
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Regine et al. 2008 (RTOG 9704) | Phase III (E-esc) | Fluorouracil & RT | Did not meet primary endpoint of OS (*) |
Note: this study was in pancreatic cancer but in practice it is extrapolated to cholangiocarcinoma. Reported efficacy is based on the 2011 update.
Preceding treatment
Chemotherapy, part 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
21-day course, followed in 1 to 2 weeks by:
Chemotherapy, part 2
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion throughout radiation therapy
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, for a total dose of 50.4 Gy. The last 5.4 Gy of the 50.4 Gy is limited to the tumor bed.
6-week course, followed in 3 to 5 weeks by:
Chemotherapy, part 3
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 3 cycles
References
- RTOG 9704: Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5;299(9):1019-26. link to original article contains verified protocol PubMed
- Update: Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the US Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26. Epub 2011 Mar 10. link to original article link to PMC article PubMed
GemOx
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GemOx: Gemcitabine & Oxaliplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Edeline et al. 2019 (PRODIGE 12-ACCORD 18-UNICANCER GI) | 2009-2014 | Phase III (E-esc) | Observation | Did not meet primary endpoint of RFS |
Preceding treatment
- Surgical resection with macroscopically curative resection
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 2
14-day cycle for 12 cycles
References
- PRODIGE 12-ACCORD 18-UNICANCER GI: Edeline J, Benabdelghani M, Bertaut A, Watelet J, Hammel P, Joly JP, Boudjema K, Fartoux L, Bouhier-Leporrier K, Jouve JL, Faroux R, Guerin-Meyer V, Kurtz JE, Assénat E, Seitz JF, Baumgaertner I, Tougeron D, de la Fouchardière C, Lombard-Bohas C, Boucher E, Stanbury T, Louvet C, Malka D, Phelip JM. Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study. J Clin Oncol. 2019 Mar 10;37(8):658-667. Epub 2019 Feb 1. link to original article PubMed
Metastatic disease, all lines of therapy
Capecitabine monotherapy
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Regimen
Study | Evidence |
---|---|
Patt et al. 2004 | Retrospective |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
21-day cycles
References
- Retrospective: Patt YZ, Hassan MM, Aguayo A, Nooka AK, Lozano RD, Curley SA, Vauthey JN, Ellis LM, Schnirer II, Wolff RA, Charnsangavej C, Brown TD. Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma. Cancer. 2004 Aug 1;101(3):578-86. link to original article PubMed
Capecitabine & Mitomycin
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kornek et al. 2004 | Randomized Phase II (E-switch-ic) | Gemcitabine & Mitomycin | Might have superior ORR |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day 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
CapeOx
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CapeOx: Capecitabine & Oxaliplatin
XELOX: XELoda (Capecitabine) & OXaliplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kim et al. 2019 (SMC 2011-05-070) | 2011-2016 | Phase III (E-switch-ic) | GEMOX | Non-inferior PFS |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
21-day cycle for 8 cycles
References
- SMC 2011-05-070: Kim ST, Kang JH, Lee J, Lee HW, Oh SY, Jang JS, Lee MA, Sohn BS, Yoon SY, Choi HJ, Hong JH, Kim MJ, Kim S, Park YS, Park JO, Lim HY. Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial. Ann Oncol. 2019 May 1;30(5):788-795. link to original article contains protocol PubMed NCT01470443
Cisplatin & Gemcitabine
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GC: Gemcitabine & Cisplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Valle et al. 2010 (ABC-02) | 2002-2008 | Phase III (E-esc) | Gemcitabine | Superior OS |
Morizane et al. 2019 (FUGA-BT) | 2013-2016 | Phase III (C) | Gemcitabine & S-1 | Seems to have non-inferior OS |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV over 60 minutes once per day on days 1 & 8, given first
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
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
- ABC-02: 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 NCT00262769
- FUGA-BT: Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, Ozaka M, Okano N, Sugimori K, Fukutomi A, Hara H, Mizuno N, Yanagimoto H, Wada K, Tobimatsu K, Yane K, Nakamori S, Yamaguchi H, Asagi A, Yukisawa S, Kojima Y, Kawabe K, Kawamoto Y, Sugimoto R, Iwai T, Nakamura K, Miyakawa H, Yamashita T, Hosokawa A, Ioka T, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J; JCOG. Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. Ann Oncol. 2019 Dec 1;30(12):1950-1958. link to original article PubMed UMIN000010667
Cisplatin, Gemcitabine, nab-Paclitaxel
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Regimen
Study | Evidence |
---|---|
Shroff et al. 2019 (MDACC 2014-0524) | Phase II |
Prolonged median PFS and OS vs reported for historical controls treated with gemcitabine-cisplatin alone.
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV over 60 minutes once per day on days 1 & 8
- Gemcitabine (Gemzar) 800 mg/m2 IV once per day on days 1 & 8
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV once per day on days 1 & 8
21-day cycle
References
- MDACC 2014-0524: Shroff RT, Javle MM, Xiao L, Kaseb AO, Varadhachary GR, Wolff RA, Raghav KPS, Iwasaki M, Masci P, Ramanathan RK, Ahn DH, Bekaii-Saab TS, Borad MJ. Gemcitabine, cisplatin, and nab-paclitaxel for the treatment of advanced biliary tract cancers: a phase 2 clinical trial. JAMA Oncol. 2019 Apr 18. [Epub ahead of print] link to original article PubMed
ECF
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ECF: Epirubicin, Cisplatin, Fluorouracil
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Rao et al. 2005 | Phase III (E-switch-ic) | FELV | Did not meet primary endpoint of OS |
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 over 21 days, started on day 1 (total dose per cycle: 4200 mg/m2)
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
Erlotinib & Bevacizumab
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Regimen
Study | Evidence |
---|---|
Lubner et al. 2010 | Phase II |
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day
- Bevacizumab (Avastin) 5 mg/kg IV once per day on days 1 & 15
28-day cycles
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
FELV
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FELV: Fluorouracil , Etoposide, LeucoVorin (Folinic acid)
Regimen variant #1, 500/120/60
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Glimelius et al. 1996 | 1991-1995 | Phase III (E-esc) | 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 third
21-day cycles
Regimen variant #2, 600/120/60
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Rao et al. 2005 | Phase III (C) | ECF | Did not meet primary endpoint of OS |
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 third
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
FULV
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FULV: 5-FU & LeucoVorin (Folinic acid)
FUFA: 5-FU (Fluorouracil) & Folinic Acid
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Glimelius et al. 1996 | 1991-1995 | Phase III (E-esc) | 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
FULV & Gemcitabine
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FULV & Gemcitabine: 5-FU, LeucoVorin (Folinic acid), Gemcitabine
Regimen
Study | Evidence |
---|---|
Gebbia et al. 2001 | Phase II |
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 600 mg/m2 IV continuous infusion over 22 hours (total dose per cycle: 1000 mg/m2)
- 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
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Regimen variant #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Valle et al. 2010 (ABC-02) | Phase III (E-de-esc) | Cisplatin & Gemcitabine | 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 variant #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
- ABC-02: 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 NCT00262769
Gemcitabine, Cisplatin, S-1
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GCS: Gemcitabine, Cisplatin, S-1
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sakai et al. 2018 (KHBO1401-MITSUBA) | Phase III (E-esc) | Cisplatin & Gemcitabine | Seems to have superior OS |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once on day 1
- Tegafur, gimeracil, oteracil (S-1) 80 mg/m2 PO once per day on days 1 to 7
14-day cycles
References
- Abstract: Sakai D, Kanai M , Kobayashi S, Eguchi H, Baba H, Seo S, Taketomi A, Takayama T, Yamaue H, Ishioka C, Sho M, Takeyama Y, Fujimoto J, Toyoda M, Shimizu J, Goto T, Yoshimura K, Hatano E, Nagano H, Ioka T. Randomized phase III study of gemcitabine, cisplatin plus S-1 (GCS) versus gemcitabine, cisplatin (GC) for advanced biliary tract cancer (KHBO1401-MITSUBA). Annals of Oncology 29 (Supplement 8): viii205–viii270, 2018 link to abstract
Gemcitabine & Mitomycin
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kornek et al. 2004 | Randomized Phase II (E-switch-ic) | 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 & nab-Paclitaxel
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NG: Nab-Paclitaxel & Gemcitabine
Regimen
Study | Evidence |
---|---|
Sahai et al. 2018 | Phase II |
Note: this regimen was intended for ECOG PS 0 to 2, and Child-Pugh score less than 8.
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 125 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- Sahai V, Catalano PJ, Zalupski MM, Lubner SJ, Menge MR, Nimeiri HS, Munshi HG, Benson AB 3rd, O'Dwyer PJ. nab-Paclitaxel and gemcitabine as first-line treatment of advanced or metastatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2018 Dec 1;4(12):1707-1712. link to original article contains protocol PubMed
Gemcitabine & S-1
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GS: Gemcitabine & S-1
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Morizane et al. 2019 (FUGA-BT) | 2013-2016 | Phase III (E-switch-ic) | Gemcitabine & Cisplatin | Seems to have non-inferior OS |
Chemotherapy
References
- FUGA-BT: Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, Ozaka M, Okano N, Sugimori K, Fukutomi A, Hara H, Mizuno N, Yanagimoto H, Wada K, Tobimatsu K, Yane K, Nakamori S, Yamaguchi H, Asagi A, Yukisawa S, Kojima Y, Kawabe K, Kawamoto Y, Sugimoto R, Iwai T, Nakamura K, Miyakawa H, Yamashita T, Hosokawa A, Ioka T, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J. Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. Ann Oncol. 2019 Dec 1;30(12):1950-1958. link to original article PubMed UMIN000010667
GemOx
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GemOx: Gemcitabine & Oxaliplatin
GEMOX: GEMcitabine & OXaliplatin
Regimen variant #1, 1000/85, bi-weekly
Study | Evidence | Efficacy |
---|---|---|
Halim et al. 2011 | Phase II | ORR: 27.5% |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once on day 1, given first
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given second
14-day cycles
Regimen variant #2, 1000/100, bi-weekly
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Lee et al. 2011 (SMC 2008-12-024) | Phase III (C) | GEMOX & Erlotinib | Might have inferior PFS |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 100 mg/m2 IV once on day 2
14-day cycles
Regimen variant #3, 1000/100, 2 weeks out of 3
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kim et al. 2019 (SMC 2011-05-070) | 2011-2016 | Phase III (C) | XELOX | Non-inferior PFS |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Oxaliplatin (Eloxatin) 100 mg/m2 IV once on day 1
21-day cycle for 8 cycles
Regimen variant #4, 1000/100 ("GEMOX-3")
Study | Evidence | Efficacy |
---|---|---|
Harder et al. 2006 | Phase II | ORR: 26% (95% CI 14–44) |
GEMOX-3: GEMcitabine & OXaliplatin, 3 visits per month
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, given first
- Oxaliplatin (Eloxatin) 100 mg/m2 IV over 2 hours once per day on days 1 & 15, given second
28-day cycles
References
- Halim A, Ebrahim MA, Saleh Y. A phase II study of outpatient biweekly gemcitabine-oxaliplatin in advanced biliary tract carcinomas. Jpn J Clin Oncol. 2011 Feb;41(2):217-24. link to original article contains verified protocol PubMed
- SMC 2008-12-024: Lee J, Park SH, Chang HM, Kim JS, Choi HJ, Lee MA, Jang JS, Jeung HC, Kang JH, Lee HW, Shin DB, Kang HJ, Sun JM, Park JO, Park YS, Kang WK, Lim HY. Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2012 Feb;13(2):181-8. Epub 2011 Dec 20. link to original article contains protocol PubMed
- SMC 2011-05-070: Kim ST, Kang JH, Lee J, Lee HW, Oh SY, Jang JS, Lee MA, Sohn BS, Yoon SY, Choi HJ, Hong JH, Kim MJ, Kim S, Park YS, Park JO, Lim HY. Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial. Ann Oncol. 2019 May 1;30(5):788-795. link to original article contains protocol PubMed NCT01470443
- Harder J, Riecken B, Kummer O, Lohrmann C, Otto F, Usadel H, Geissler M, Opitz O, Henss H. Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer. Br J Cancer. 2006 Oct 9;95(7):848-52. link to PMC article contains verified protocol PubMed
GEMOX-B
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GEMOX-B: GEMcitabine, OXaliplatin, Bevacizumab
Regimen
Study | Evidence |
---|---|
Zhu et al. 2009 (MGH 05-349) | 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 third
Targeted therapy
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15, given first
28-day cycles
References
- MGH 05-349: 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
Ivosidenib monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Abou-Alfa et al. 2019 (ClarIDHy) | Phase III (E-esc) | Placebo | Superior PFS |
Note: Patients with unresectable or metastatic disease with IDH1 mutation with progression after at least one prior systemic therapy.
Targeted therapy
- Ivosidenib (Tibsovo) 500 mg PO once per day
Continued indefinitely
References
- Abstract: GK Abou-Alfa, T Macarulla Mercade, M Javle, RK Kelley, S Lubner, J Adeva, JM Cleary, DV Catenacci, MJ Borad, JA Bridgewater, WP Harris, AG Murphy, D-Y Oh, J Whisenant, B Wu, L Jiang, C Gliser, SS Pandya, JW Valle, AX Zhu. ClarIDHy: A global, phase III, randomized, double-blind study of ivosidenib (IVO) vs placebo in pateints with advanced cholangiocarcinoma (CC) with an isocitrate dehydrogenase 1 (IDH1) mutation. Annals of Oncology, Volume 30, Issue Supplement-5, October 2019, mdz394.027. link to abstract
Pembrolizumab monotherapy
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Regimen
Study | Evidence |
---|---|
Le et al. 2017 (KEYNOTE-016) | Phase II, <20 pts of this subtype |
Note: KEYNOTE-016 was an expansion to a CRC-specific trial.
Immunotherapy
- Pembrolizumab (Keytruda) 10 mg/kg IV once on day 1
14-day cycle for up to 52 cycles (2 years)
References
- KEYNOTE-016: Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8. link to original article link to PMC article contains verified protocol in supplement PubMed
Pemigatinib monotherapy
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Regimen
Study | Evidence |
---|---|
Abou-Alfa et al. 2020 (FIGHT-202) | Phase II (RT) |
Note: Patients with previously treated unresectable or metastatic disease.
Biomarker eligibility criteria
- Fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement
Targeted therapy
- Pemigatinib (Pemazyre) 13.5 mg PO once per day on days 1 to 14
21-day cycles
References
- FIGHT-202: Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, Paulson AS, Borad MJ, Gallinson D, Murphy AG, Oh DY, Dotan E, Catenacci DV, Van Cutsem E, Ji T, Lihou CF, Zhen H, Féliz L, Vogel A. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020 Mar 20:S1470-2045(20)30109-1. [Epub ahead of print] link to original article contains verified protocol in supplement PubMed
Regorafenib monotherapy
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Regimen
Study | Evidence |
---|---|
Sun et al. 2019 | Phase II |
Only studied in patients with advanced biliary cancer who failed at least 1 line of systemic therapy.
Targeted therapy
- Regorafenib (Stivarga) 120 mg PO once per day on days 1 to 21
28-day cycles
References
- Sun W, Patel A, Normolle A, Patel K, Ohr J, Lee JJ, Bahary N, Chu E, Streeter N, Drummond S. A phase 2 trial of regorafenib as a single agent in patients with chemotherapy-refractory, advanced, and metastatic biliary tract adenocarcinoma. Cancer. 2019 Mar 15;125(6):902-909. Epub 2018 Dec 18. link to original article link to PMC article PubMed