Difference between revisions of "Cholangiocarcinoma"
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===References=== | ===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. [https://doi.org/10.1093/annonc/mdz058 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30785198/ PubMed] [https://clinicaltrials.gov/study/NCT01470443 NCT01470443] | #'''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. [https://doi.org/10.1093/annonc/mdz058 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30785198/ PubMed] [https://clinicaltrials.gov/study/NCT01470443 NCT01470443] | ||
− | ==Cisplatin & Gemcitabine (GC) {{#subobject: | + | ==Cisplatin & Gemcitabine (GC) {{#subobject:af0357|Regimen=1}}== |
GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''isplatin | GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''isplatin | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ===Regimen {{#subobject:cb3ttq|Variant=1}}=== | + | ===Regimen variant #1, up to 8 cycles {{#subobject:cb3ttq|Variant=1}}=== |
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
Line 249: | Line 249: | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa0908721 Valle et al. 2010 (ABC-02)] | ||
+ | |2002-2008 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[#Gemcitabine_monotherapy_2|Gemcitabine]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 11.7 vs 8.1 mo<br>(HR 0.64, 95% CI 0.52-0.80) | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdz402 Morizane et al. 2019 (FUGA-BT)] | ||
+ | |2013-2016 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Gemcitabine_.26_S-1|Gemcitabine & S-1]] | ||
+ | | style="background-color:#eeee01" |Seems to have non-inferior OS | ||
|- | |- | ||
|[https://doi.org/10.1056/EVIDoa2200015 Oh et al. 2022 (TOPAZ-1)] | |[https://doi.org/10.1056/EVIDoa2200015 Oh et al. 2022 (TOPAZ-1)] | ||
Line 268: | Line 280: | ||
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
'''21-day cycle for up to 8 cycles''' | '''21-day cycle for up to 8 cycles''' | ||
+ | </div></div><br><div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, indefinite {{#subobject:cb3c9d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10086809/ Ioka et al. 2022 (KHBO1401-MITSUBA)] | ||
+ | |2014-2016 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Gemcitabine.2C_Cisplatin.2C_S-1|GCS]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8, '''given first''' | ||
+ | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8, '''given second''' | ||
+ | ====Supportive therapy==== | ||
+ | *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 cycles''' | ||
</div></div> | </div></div> | ||
===References=== | ===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. [https://doi.org/10.1056/NEJMoa0908721 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20375404/ PubMed] [https://clinicaltrials.gov/study/NCT00262769 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. [https://doi.org/10.1093/annonc/mdz402 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31566666/ PubMed] UMIN000010667 | ||
#'''TOPAZ-1:''' Oh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, Kim JW, Suksombooncharoen T, Ah Lee M, Kitano M, Burris H, Bouattour M, Tanasanvimon S, McNamara MG, Zaucha R, Avallone A, Tan B, Cundom J, Lee C kun, Takahashi H, Ikeda M, Chen JS, Wang J, Makowsky M, Rokutanda N, He P, Kurland JF, Cohen G, Valle JW; TOPAZ-1 Investigators. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evidence. 2022 Aug;1(8):EVIDoa2200015. Epub 2022 Jun 1. [https://doi.org/10.1056/EVIDoa2200015 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38319896/ PubMed] [https://clinicaltrials.gov/study/NCT03875235 NCT03875235] | #'''TOPAZ-1:''' Oh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, Kim JW, Suksombooncharoen T, Ah Lee M, Kitano M, Burris H, Bouattour M, Tanasanvimon S, McNamara MG, Zaucha R, Avallone A, Tan B, Cundom J, Lee C kun, Takahashi H, Ikeda M, Chen JS, Wang J, Makowsky M, Rokutanda N, He P, Kurland JF, Cohen G, Valle JW; TOPAZ-1 Investigators. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evidence. 2022 Aug;1(8):EVIDoa2200015. Epub 2022 Jun 1. [https://doi.org/10.1056/EVIDoa2200015 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38319896/ PubMed] [https://clinicaltrials.gov/study/NCT03875235 NCT03875235] | ||
##'''PRO analysis:''' Burris HA 3rd, Okusaka T, Vogel A, Lee MA, Takahashi H, Breder V, Blanc JF, Li J, Bachini M, Żotkiewicz M, Abraham J, Patel N, Wang J, Ali M, Rokutanda N, Cohen G, Oh DY. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2024 May;25(5):626-635. [https://doi.org/10.1016/s1470-2045(24)00082-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38697156/ PubMed] | ##'''PRO analysis:''' Burris HA 3rd, Okusaka T, Vogel A, Lee MA, Takahashi H, Breder V, Blanc JF, Li J, Bachini M, Żotkiewicz M, Abraham J, Patel N, Wang J, Ali M, Rokutanda N, Cohen G, Oh DY. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2024 May;25(5):626-635. [https://doi.org/10.1016/s1470-2045(24)00082-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38697156/ PubMed] | ||
+ | #'''KHBO1401-MITSUBA:''' Ioka T, Kanai M, Kobayashi S, Sakai D, Eguchi H, Baba H, Seo S, Taketomi A, Takayama T, Yamaue H, Takahashi M, Sho M, Kamei K, Fujimoto J, Toyoda M, Shimizu J, Goto T, Shindo Y, Yoshimura K, Hatano E, Nagano H; Kansai Hepatobiliary Oncology Group (KHBO). Randomized phase III study of gemcitabine, cisplatin plus S-1 versus gemcitabine, cisplatin for advanced biliary tract cancer (KHBO1401- MITSUBA). J Hepatobiliary Pancreat Sci. 2023 Jan;30(1):102-110. Epub 2022 Aug 9. [https://doi.org/10.1002/jhbp.1219 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10086809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35900311/ PubMed] [https://clinicaltrials.gov/study/NCT02182778 NCT02182778] | ||
#'''KEYNOTE-966:''' Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klümpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. Epub 2023 Apr 14. [https://doi.org/10.1016/s0140-6736(23)00727-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/37075781/ PubMed] [https://clinicaltrials.gov/study/NCT04003636 NCT04003636] | #'''KEYNOTE-966:''' Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klümpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. Epub 2023 Apr 14. [https://doi.org/10.1016/s0140-6736(23)00727-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/37075781/ PubMed] [https://clinicaltrials.gov/study/NCT04003636 NCT04003636] | ||
+ | #'''FIGHT-302:''' [https://clinicaltrials.gov/study/NCT03656536 NCT03656536] | ||
+ | #'''FOENIX-CCA3:''' [https://clinicaltrials.gov/study/NCT04093362 NCT04093362] | ||
+ | #'''NuTide:121:''' [https://clinicaltrials.gov/study/NCT04163900 NCT04163900] | ||
+ | #'''PROOF 301:''' [https://clinicaltrials.gov/study/NCT03773302 NCT03773302] | ||
+ | #'''SWOG S1815:''' [https://clinicaltrials.gov/study/NCT03768414 NCT03768414] | ||
+ | |||
==Cisplatin & Gemcitabine (GC) & Durvalumab {{#subobject:dub057|Regimen=1}}== | ==Cisplatin & Gemcitabine (GC) & Durvalumab {{#subobject:dub057|Regimen=1}}== | ||
GC & Durvalumab: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin, Durvalumab | GC & Durvalumab: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin, Durvalumab |
Revision as of 15:16, 30 May 2024
Section editor | |
---|---|
Eric I. Marks, MD Boston University Boston, MA, USA |
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.
Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASCO
- 2019: Shroff et al. Adjuvant therapy for resected biliary tract cancer: ASCO Clinical Practice Guideline PubMed
ESMO
- 2022: Vogel et al. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed
- 2016: Valle et al. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2011: Eckel et al. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Eckel et al. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Eckel & Jelic. Biliary cancer: ESMO clinical recommendation for diagnosis, treatment and follow-up PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Biliary Tract Cancers.
Adjuvant therapy
Capecitabine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Primrose et al. 2019 (BILCAP) | 2006-2014 | Phase 3 (E-esc) | Observation | Did not meet primary endpoint of OS1 Median OS: 49.6 vs 36.1 mo (aHR 0.84, 95% CI 0.67-1.06) |
1Reported efficacy is based on the 2022 update.
Note: Chemotherapy start date 8 to 16 weeks after surgery
Preceding treatment
- Surgical resection with macroscopically curative resection
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, Anthoney 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 contains dosing details in abstract PubMed NCT00363584
- Update: Bridgewater J, Fletcher P, Palmer DH, Malik HZ, Prasad R, Mirza D, Anthoney A, Corrie P, Falk S, Finch-Jones M, Wasan H, Ross P, Wall L, Wadsley J, Evans TR, Stocken D, Stubbs C, Praseedom R, Ma YT, Davidson B, Neoptolemos J, Iveson T, Cunningham D, Garden OJ, Valle JW, Primrose J; BILCAP study group. Long-Term Outcomes and Exploratory Analyses of the Randomized Phase III BILCAP Study. J Clin Oncol. 2022 Jun 20;40(18):2048-2057. Epub 2022 Mar 22. link to original article PubMed
Capecitabine & Gemcitabine
GemCap: Gemcitabine & Capecitabine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Ben-Josef et al. 2015 (SWOG S0809) | 2008-2012 | Phase 2 |
Preceding treatment
Chemotherapy
- Capecitabine (Xeloda) 750 mg/m2 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 consolidation
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 dosing details in manuscript PubMed NCT00789958
Capecitabine & RT
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Ben-Josef et al. 2015 (SWOG S0809) | 2008-2012 | Phase 2 |
Preceding treatment
- Adjuvant GemCap x 4
Chemotherapy
- Capecitabine (Xeloda) 665 mg/m2 PO twice per day on days 1 to 14
Radiotherapy
- Concurrent radiation therapy 5400 cGy in 30 fractions, given 5 times per week
40-day course
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 dosing details in manuscript PubMed NCT00789958
Gemcitabine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ebata et al. 2018 (BCAT) | 2007-2011 | Phase 3 (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 UMIN000000820
Gemcitabine/Fluorouracil & RT
Gemcitabine/Fluorouracil & RT: Gemcitabine alternating with Fluorouracil & Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Regine et al. 2008 (RTOG 9704) | 1998-2002 | Phase 3 (E-esc) | Fluorouracil & RT | Did not meet primary endpoint of OS1 |
1Reported efficacy is based on the 2011 update.
Note: this study was in pancreatic cancer but in practice it is extrapolated to cholangiocarcinoma.
Preceding treatment
Chemotherapy
- Gemcitabine (Gemzar) as follows:
- Cycles 1, 3, 4, 5: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
- Fluorouracil (5-FU) as follows:
- Cycle 2 (chemoradiation): 250 mg/m2/day IV continuous infusion throughout radiation therapy
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 2 (chemoradiation): 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38 (28 fractions for a total dose of 5040 cGy). The last 540 cGy of the 5040 cGy is limited to the tumor bed.
4- to 5-week course, then 9- to 11-week course, then 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 dosing details in manuscript PubMed NCT00003216
- 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
GemOx: Gemcitabine & Oxaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Edeline et al. 2019 (PRODIGE 12-ACCORD 18-UNICANCER GI) | 2009-2014 | Phase 3 (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 NCT01313377
Metastatic, first-line therapy
CapeOx
CapeOx: Capecitabine & Oxaliplatin
XELOX: XELoda (Capecitabine) & OXaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kim et al. 2019 (SMC 2011-05-070) | 2011-2016 | Phase 3 (E-switch-ic) | GEMOX | Non-inferior PFS6 (primary endpoint) PFS6: 46.7% vs 44.5% |
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 dosing details in abstract PubMed NCT01470443
Cisplatin & Gemcitabine (GC)
GC: Gemcitabine & Cisplatin
Regimen variant #1, up to 8 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Valle et al. 2010 (ABC-02) | 2002-2008 | Phase 3 (E-esc) | Gemcitabine | Superior OS (primary endpoint) Median OS: 11.7 vs 8.1 mo (HR 0.64, 95% CI 0.52-0.80) |
Morizane et al. 2019 (FUGA-BT) | 2013-2016 | Phase 3 (C) | Gemcitabine & S-1 | Seems to have non-inferior OS |
Oh et al. 2022 (TOPAZ-1) | 2019-04 to 2020-12 | Phase 3 (C) | GC & Durvalumab | Seems to have inferior OS |
Kelley et al. 2023 (KEYNOTE-966) | 2019-10-04 to 2021-06-08 | Phase 3 (C) | GC & Pembrolizumab | Seems to have inferior OS |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 8 cycles
Regimen variant #2, indefinite
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ioka et al. 2022 (KHBO1401-MITSUBA) | 2014-2016 | Phase 3 (C) | GCS | Might have 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 therapy
- 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 cycles
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 dosing details in manuscript 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
- TOPAZ-1: Oh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, Kim JW, Suksombooncharoen T, Ah Lee M, Kitano M, Burris H, Bouattour M, Tanasanvimon S, McNamara MG, Zaucha R, Avallone A, Tan B, Cundom J, Lee C kun, Takahashi H, Ikeda M, Chen JS, Wang J, Makowsky M, Rokutanda N, He P, Kurland JF, Cohen G, Valle JW; TOPAZ-1 Investigators. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evidence. 2022 Aug;1(8):EVIDoa2200015. Epub 2022 Jun 1. link to original article contains dosing details in manuscript PubMed NCT03875235
- PRO analysis: Burris HA 3rd, Okusaka T, Vogel A, Lee MA, Takahashi H, Breder V, Blanc JF, Li J, Bachini M, Żotkiewicz M, Abraham J, Patel N, Wang J, Ali M, Rokutanda N, Cohen G, Oh DY. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2024 May;25(5):626-635. link to original article PubMed
- KHBO1401-MITSUBA: Ioka T, Kanai M, Kobayashi S, Sakai D, Eguchi H, Baba H, Seo S, Taketomi A, Takayama T, Yamaue H, Takahashi M, Sho M, Kamei K, Fujimoto J, Toyoda M, Shimizu J, Goto T, Shindo Y, Yoshimura K, Hatano E, Nagano H; Kansai Hepatobiliary Oncology Group (KHBO). Randomized phase III study of gemcitabine, cisplatin plus S-1 versus gemcitabine, cisplatin for advanced biliary tract cancer (KHBO1401- MITSUBA). J Hepatobiliary Pancreat Sci. 2023 Jan;30(1):102-110. Epub 2022 Aug 9. link to original article link to PMC article PubMed NCT02182778
- KEYNOTE-966: Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klümpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. Epub 2023 Apr 14. link to original article contains dosing details in abstract PubMed NCT04003636
- FIGHT-302: NCT03656536
- FOENIX-CCA3: NCT04093362
- NuTide:121: NCT04163900
- PROOF 301: NCT03773302
- SWOG S1815: NCT03768414
Cisplatin & Gemcitabine (GC) & Durvalumab
GC & Durvalumab: Gemcitabine, Cisplatin, Durvalumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oh et al. 2022 (TOPAZ-1) | 2019-04 to 2020-12 | Phase 3 (E-RT-esc) | GC | Seems to have superior OS (primary endpoint) Median OS: 12.8 vs 11.5 mo (HR 0.80, 95% CI 0.66-0.97) |
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 up to 8: 25 mg/m2 IV once per day on days 1 & 8
- Gemcitabine (Gemzar) as follows:
- Cycles 1 up to 8: 1000 mg/m2 IV once per day on days 1 & 8
Immunotherapy
- Durvalumab (Imfinzi) as follows:
- Cycles 1 up to 8: 1500 mg IV once on day 1
- Cycle 9 onwards: 1500 mg IV once on day 1
21-day cycle for up to 8 cycles, then 28-day cycles
References
- TOPAZ-1: Oh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, Kim JW, Suksombooncharoen T, Ah Lee M, Kitano M, Burris H, Bouattour M, Tanasanvimon S, McNamara MG, Zaucha R, Avallone A, Tan B, Cundom J, Lee C kun, Takahashi H, Ikeda M, Chen JS, Wang J, Makowsky M, Rokutanda N, He P, Kurland JF, Cohen G, Valle JW; TOPAZ-1 Investigators. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evidence. 2022 Aug;1(8):EVIDoa2200015. Epub 2022 Jun 1. link to original article contains dosing details in manuscript PubMed NCT03875235
- PRO analysis: Burris HA 3rd, Okusaka T, Vogel A, Lee MA, Takahashi H, Breder V, Blanc JF, Li J, Bachini M, Żotkiewicz M, Abraham J, Patel N, Wang J, Ali M, Rokutanda N, Cohen G, Oh DY. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2024 May;25(5):626-635. link to original article PubMed
Cisplatin & Gemcitabine (GC) & nab-Paclitaxel
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Shroff et al. 2019 (MDACC 2014-0524) | 2015-2017 | Phase 2 |
Note: this regimen prolonged median PFS and OS vs reported for historical controls treated with gemcitabine-cisplatin alone. This is the dose after a mid-protocol amendment for hematologic toxicity.
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 cycles
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 Jun 1;5(6):824-830. Epub 2019 Apr 18. link to original article contains dosing details in abstract link to PMC article PubMed NCT02392637
Cisplatin & Gemcitabine (GC) & Pembrolizumab
GC & Pembrolizumab: Gemcitabine, Cisplatin, Pembrolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kelley et al. 2023 (KEYNOTE-966) | 2019-10-04 to 2021-06-08 | Phase 3 (E-esc) | GC | Seems to have superior OS (primary endpoint) Median OS: 12.7 vs 10.9 mo (HR 0.83, 95% CI 0.72-0.95) |
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 up to 8: 25 mg/m2 IV once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
Immunotherapy
- Pembrolizumab (Keytruda) as follows:
- Cycles 1 up to 35: 200 mg IV once on day 1
21-day cycles
References
- KEYNOTE-966: Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klümpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. Epub 2023 Apr 14. link to original article contains dosing details in abstract PubMed NCT04003636
Erlotinib & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Lubner et al. 2010 (MC044G) | 2006-08 to 2008-04 | Phase 2 |
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 28
- Bevacizumab (Avastin) 5 mg/kg IV once per day on days 1 & 15
28-day cycles
References
- MC044G: 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 dosing details in manuscript link to PMC article PubMed NCT00356889
FELV
FELV: Fluorouracil , Etoposide & LeucoVorin (Folinic acid)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Glimelius et al. 1996 | 1991-1995 | Phase 3 (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
- Leucovorin (Folinic acid) 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 dosing details in manuscript PubMed content property of HemOnc.org
FULV
FULV: 5-FU & LeucoVorin
FUFA: 5-FU (Fluorouracil) & Folinic Acid
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Glimelius et al. 1996 | 1991-1995 | Phase 3 (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
- Leucovorin (Folinic acid) 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 dosing details in manuscript PubMed
FULV & Gemcitabine
FULV & Gemcitabine: 5-FU, LeucoVorin, Gemcitabine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Gebbia et al. 2001 | 1997-2000 | Phase 2 |
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)
- Leucovorin (Folinic acid) 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 dosing details in manuscript PubMed
Gemcitabine monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Valle et al. 2010 (ABC-02) | 2002-2008 | Phase 3 (C) | 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 | Dates of enrollment | Evidence |
---|---|---|
Gebbia et al. 2001 | 1997-2000 | Phase 2 |
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 dosing details in manuscript 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 dosing details in manuscript PubMed NCT00262769
Gemcitabine & Mitomycin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kornek et al. 2004 | 2000-2001 | Randomized Phase 2 (E-switch-ic) | Capecitabine & Mitomycin | Might have inferior ORR (primary endpoint) |
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 therapy
- 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 dosing details in manuscript PubMed
Gemcitabine & nab-Paclitaxel
NG: Nab-Paclitaxel & Gemcitabine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Sahai et al. 2018 (PrE0204) | 2014-2016 | Phase 2 |
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
- PrE0204: 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 dosing details in abstract link to PMC article PubMed NCT02181634
Gemcitabine & S-1
GS: Gemcitabine & S-1
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Morizane et al. 2019 (FUGA-BT) | 2013-2016 | Phase 3 (E-switch-ic) | Gemcitabine & Cisplatin | Seems to have non-inferior OS (primary endpoint) Median OS: 15.1 vs 13.4 mo (HR 0.945, 90% CI 0.78-1.15) |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Tegafur, gimeracil, oteracil (S-1) by the following BSA-based criteria:
- Less than 1.25 m2: 30 mg PO twice per day on days 1 to 14
- Between 1.25 m2 and 1.5 m2: 40 mg PO twice per day on days 1 to 14
- 1.5 m2 or more: 50 mg PO twice per day on days 1 to 14
21-day cycles
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; 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 contains dosing details in manuscript PubMed UMIN000010667
Gemcitabine, Cisplatin, S-1
GCS: Gemcitabine, Cisplatin, S-1
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ioka et al. 2022 (KHBO1401-MITSUBA) | 2014-2016 | Phase 3 (E-esc) | Cisplatin & Gemcitabine | Might have superior OS (primary endpoint) Median OS: 13.5 vs 12.6 mo (HR 0.79, 90% CI 0.63-0.996) |
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
- KHBO1401-MITSUBA: Ioka T, Kanai M, Kobayashi S, Sakai D, Eguchi H, Baba H, Seo S, Taketomi A, Takayama T, Yamaue H, Takahashi M, Sho M, Kamei K, Fujimoto J, Toyoda M, Shimizu J, Goto T, Shindo Y, Yoshimura K, Hatano E, Nagano H; Kansai Hepatobiliary Oncology Group (KHBO). Randomized phase III study of gemcitabine, cisplatin plus S-1 versus gemcitabine, cisplatin for advanced biliary tract cancer (KHBO1401- MITSUBA). J Hepatobiliary Pancreat Sci. 2023 Jan;30(1):102-110. Epub 2022 Aug 9. link to original article contains dosing details in abstract link to PMC article PubMed NCT02182778
GemOx
GemOx: Gemcitabine & Oxaliplatin
GEMOX: GEMcitabine & OXaliplatin
Regimen variant #1, 1000/85, bi-weekly
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Halim et al. 2010 | 2005-12 to 2009-11 | Phase 2 | 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 x 8
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kim et al. 2019 (SMC 2011-05-070) | 2011-2016 | Phase 3 (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 #3, 1000/100, indefinite bi-weekly
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2011 (SMC 2008-12-024) | 2009-02-16 to 2010-08-01 | Phase 3 (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 #4, indefinite 1000/100 ("GEMOX-3")
GEMOX-3: GEMcitabine & OXaliplatin, 3 visits per month
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Harder et al. 2006 | 2002-2005 | Phase 2 | ORR: 26% (95% CI 14–44) |
Note: This study was technically open to previously treated patients, but only 1 (3%) had received prior chemoradiotherapy, and none had received prior systemic therapy.
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
- 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. Epub 2006 Sep 12. link to original article link to PMC article contains dosing details in manuscript PubMed
- 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. Epub 2010 Nov 8. link to original article contains dosing details in manuscript 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 dosing details in abstract PubMed NCT01149122
- 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 dosing details in abstract PubMed NCT01470443
- KN035-BTC: NCT03478488
GEMOX-B
GEMOX-B: GEMcitabine, OXaliplatin, Bevacizumab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Zhu et al. 2009 (MGH 05-349) | 2006-2007 | Phase 2 |
Note: Up to one prior line of therapy was allowed, but the majority (91%) of patients in this study were untreated.
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 dosing details in manuscript PubMed NCT00361231
Metastatic disease, second-line
mFOLFOX6
mFOLFOX6: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lamarca et al. 2021 (ABC-06) | 2014-2018 | Phase 3 (E-esc) | Active symptom control | Seems to have superior OS (primary endpoint) Median OS: 6.2 vs 5.3 mo (HR 0.69, 95% CI 0.50-0.97) |
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
- Leucovorin (Folinic acid) 350 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
14-day cycle for up to 12 cycles
References
- ABC-06: Lamarca A, Palmer DH, Wasan HS, Ross PJ, Ma YT, Arora A, Falk S, Gillmore R, Wadsley J, Patel K, Anthoney A, Maraveyas A, Iveson T, Waters JS, Hobbs C, Barber S, Ryder WD, Ramage J, Davies LM, Bridgewater JA, Valle JW; Advanced Biliary Cancer Working Group. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021 May;22(5):690-701. Epub 2021 Mar 30. link to original article link to PMC article contains dosing details in abstract PubMed NCT01926236
mFOLFOX6 (L-Leucovorin)
mFOLFOX6: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lamarca et al. 2021 (ABC-06) | 2014-2018 | Phase 3 (E-esc) | Active symptom control | Seems to have superior OS (primary endpoint) Median OS: 6.2 vs 5.3 mo (HR 0.69, 95% CI 0.50-0.97) |
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
- Levoleucovorin (Fusilev) 175 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
14-day cycle for up to 12 cycles
References
- ABC-06: Lamarca A, Palmer DH, Wasan HS, Ross PJ, Ma YT, Arora A, Falk S, Gillmore R, Wadsley J, Patel K, Anthoney A, Maraveyas A, Iveson T, Waters JS, Hobbs C, Barber S, Ryder WD, Ramage J, Davies LM, Bridgewater JA, Valle JW; Advanced Biliary Cancer Working Group. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021 May;22(5):690-701. Epub 2021 Mar 30. link to original article link to PMC article contains dosing details in abstract PubMed NCT01926236
Metastatic disease, subsequent lines of therapy
Futibatinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence |
---|---|---|
Goyal et al. 2023 (FOENIX-CCA2) | 2016-04-16 to 2019-11-29 | Phase 1/2 (RT) |
Biomarker eligibility criteria
- Fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement
References
- FOENIX-CCA2: Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, Abrams TA, Furuse J, Kelley RK, Cassier PA, Klümpen HJ, Chang HM, Chen LT, Tabernero J, Oh DY, Mahipal A, Moehler M, Mitchell EP, Komatsu Y, Masuda K, Ahn D, Epstein RS, Halim AB, Fu Y, Salimi T, Wacheck V, He Y, Liu M, Benhadji KA, Bridgewater JA; FOENIX-CCA2 Study Investigators. Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. N Engl J Med. 2023 Jan 19;388(3):228-239. link to original article contains dosing details in abstract PubMed NCT02052778
Infigratinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence |
---|---|---|
Javle et al. 2017 (CBGJ398X2204) | 2014-2020 | Phase 2 (RT) |
Biomarker eligibility criteria
- FGFR2 gene fusions or translocations or other FGFR genetic alterations
References
- CBGJ398X2204: Javle M, Lowery M, Shroff RT, Weiss KH, Springfeld C, Borad MJ, Ramanathan RK, Goyal L, Sadeghi S, Macarulla T, El-Khoueiry A, Kelley RK, Borbath I, Choo SP, Oh DY, Philip PA, Chen LT, Reungwetwattana T, Van Cutsem E, Yeh KH, Ciombor K, Finn RS, Patel A, Sen S, Porter D, Isaacs R, Zhu AX, Abou-Alfa GK, Bekaii-Saab T. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol. 2018 Jan 20;36(3):276-282. Epub 2017 Nov 28. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02150967
- Update: Javle M, Roychowdhury S, Kelley RK, Sadeghi S, Macarulla T, Weiss KH, Waldschmidt DT, Goyal L, Borbath I, El-Khoueiry A, Borad MJ, Yong WP, Philip PA, Bitzer M, Tanasanvimon S, Li A, Pande A, Soifer HS, Shepherd SP, Moran S, Zhu AX, Bekaii-Saab TS, Abou-Alfa GK. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol Hepatol. 2021 Oct;6(10):803-815. Epub 2021 Aug 3. link to original article PubMed
Ivosidenib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Abou-Alfa et al. 2020 (ClarIDHy) | 2017-2019 | Phase 3 (E-RT-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 2.7 vs 1.4 mo (HR 0.37, 95% CI 0.25-0.54) |
Note: Patients with unresectable or metastatic disease with IDH1 mutation with progression after at least one prior systemic therapy.
Biomarker eligibility criteria
- IDH1 mutation
References
- ClarIDHy: Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DV, Borad MJ, Bridgewater J, Harris WP, Murphy AG, Oh DY, Whisenant J, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Fan B, Wu B, Chamberlain CX, Jiang L, Gliser C, Pandya SS, Valle JW, Zhu AX. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Jun;21(6):796-807. Epub 2020 May 13. Erratum in: Lancet Oncol. 2020 Oct;21(10):e462. link to original article contains dosing details in abstract link to PMC article PubMed NCT02989857
- Update: Zhu AX, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DVT, Borad MJ, Bridgewater JA, Harris WP, Murphy AG, Oh DY, Whisenant JR, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Chamberlain CX, Aguado-Fraile E, Choe S, Wu B, Liu H, Gliser C, Pandya SS, Valle JW, Abou-Alfa GK. Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial. JAMA Oncol. 2021 Nov 1;7(11):1669-1677. link to original article link to PMC article PubMed
Lenvatinib & Pembrolizumab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Awaiting publication (LEAP-005) | 2019-ongoing | Phase 2 |
Note: Dosing details are from ASCO abstract #321 (2021).
Targeted therapy
- Lenvatinib (Lenvima) 20 mg PO once per day
Immunotherapy
- Pembrolizumab (Keytruda) as follows:
- Cycles 1 to 35: 200 mg IV once on day 1
35-day cycles
References
- LEAP-005: NCT03797326
Nivolumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Kim et al. 2020 (MCC-18684) | 2016-2018 | Phase 2 |
Prior treatment criteria
- 1 to 3 prior lines of therapy
Immunotherapy
- Nivolumab (Opdivo) as follows:
- Cycles 1 to 8: 240 mg IV once on day 1
- Cycle 9 onwards: 480 mg IV once on day 1
14-day cycle for 8 cycles, then 28-day cycles
References
- MCC-18684: Kim RD, Chung V, Alese OB, El-Rayes BF, Li D, Al-Toubah TE, Schell MJ, Zhou JM, Mahipal A, Kim BH, Kim DW. A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer. JAMA Oncol. 2020 Jun 1;6(6):888-894. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02829918
Pembrolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Le et al. 2015 (KEYNOTE-016) | 2013-09 to 2016-09 | Phase 2, fewer than 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, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. Epub 2015 May 30. link to original article contains dosing details in abstract link to PMC article PubMed NCT01876511
- Update: 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 dosing details in supplement PubMed
Pemigatinib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Abou-Alfa et al. 2020 (FIGHT-202) | 2017-2019 | Phase 2 (RT) |
Note: Patients with previously treated unresectable or metastatic disease.
Biomarker eligibility criteria
- Fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement
Prior treatment criteria
- 1+ systemic anticancer therapies
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 May;21(5):671-684. Epub 2020 Mar 20 link to original article contains dosing details in supplement link to PMC article PubMed NCT02924376
Regorafenib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Sun et al. 2019 (UPMC 13-100) | 2014-2017 | Phase 2 |
Prior treatment criteria
- Failure of at least 1 line of systemic therapy
References
- UPMC 13-100: 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 contains dosing details in manuscript PubMed NCT02053376