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Page editor		Section editor
	Emily Mann, MD Boston University Boston, MA, USA		Eric I. Marks, MD Boston University Boston, MA, USA

21 regimens on this page 26 variants on this page

Note: there is some overlap, especially in the earlier literature, between treatment regimens for gallbladder cancer and those for pancreatic adenocarcinoma, periampullary adenocarcinoma, and cholangiocarcinoma; please see those pages for additional regimens.
Are you looking for a regimen but can't find it here? 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.

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

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.
79 of 447 enrolled patients (17.7%) had primary gallbladder cancer. Note: Chemotherapy start date 8-16 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 PubMed NCT00363584
1. 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

25 of 79 enrolled patients (32%) had primary gallbladder cancer.

Preceding treatment

Surgical resection

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

Adjuvant 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 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

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

38 of 194 enrolled patients (20%) had primary gallbladder cancer.

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

S-1 monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Nakachi et al 2023 (ASCOT)	2013-09-09 to 2018-06-22	Phase 3 (E-esc)	Observation	Superior OS (primary endpoint) OS36: 77.1% vs 67.6% (HR 0.69, 95% CI 0.51-0.94)

Preceding treatment

Surgical resection

Chemotherapy

Tegafur, gimeracil, oteracil (S-1) by the following BSA-based criteria:
- Less than 1.25 m²: 40 mg PO twice per day on days 1 to 28
- 1.25 m² up to 1.5 m²: 50 mg PO twice per day on days 1 to 28
- 1.5 m² or more: 60 mg PO twice per day on days 1 to 28

42-day cycle for up to 4 cycles

References

ASCOT: Nakachi K, Ikeda M, Konishi M, Nomura S, Katayama H, Kataoka T, Todaka A, Yanagimoto H, Morinaga S, Kobayashi S, Shimada K, Takahashi Y, Nakagohri T, Gotoh K, Kamata K, Shimizu Y, Ueno M, Ishii H, Okusaka T, Furuse J; Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG). Adjuvant S-1 compared with observation in resected biliary tract cancer (JCOG1202, ASCOT): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet. 2023 Jan 21;401(10372):195-203. PMID: 36681415. link to original article contains dosing details in abstract PubMed UMIN000011688

Metastatic or unresectable disease, all lines of therapy

Capecitabine monotherapy

Regimen

Study	Evidence
Patt et al. 2004	Retrospective

Note: 3 of 37 patients (8%) had primary gallbladder cancer.

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

CAPIRI

CAPIRI: CAPecitabine & IRInotecan

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ramaswami et al. 2020 (GB-SELECT)	2018-2020	Randomized Phase 2 (E-esc)	Irinotecan	Did not meet primary endpoint of OS6

Prior treatment criteria

Progression after prior gemcitabine-based chemotherapy

Chemotherapy

Capecitabine (Xeloda) 1700 mg/m²/day PO on days 1 to 14
Irinotecan (Camptosar) 200 mg/m² IV bolus once on day 1

21-day cycles

References

GB-SELECT: Ramaswamy A, Ostwal V, Sharma A, Bhargava P, Srinivas S, Goel M, Patkar S, Mandavkar S, Jadhav P, Parulekar M, Choudhari A, Gupta S. Efficacy of Capecitabine Plus Irinotecan vs Irinotecan Monotherapy as Second-line Treatment in Patients With Advanced Gallbladder Cancer: A Multicenter Phase 2 Randomized Clinical Trial (GB-SELECT). JAMA Oncol. 2021 Mar 1;7(3):436-439. Epub 2020 Dec 3. link to original article contains dosing details in manuscript link to PMC article PubMed CTRI/2017/10/010112

Capecitabine & Mitomycin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kornek et al. 2004	2000-2001	Randomized Phase 2 (E-switch-ic)	Gemcitabine & Mitomycin	Might have superior ORR (primary endpoint)

Note: 14 of 51 enrolled patients (27%) had primary gallbladder cancer.

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 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

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 PFS6: 46.7% vs 44.5%

Note: 61 of 222 enrolled patients (22%) had primary gallbladder cancer.

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

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)
Sharma et al. 2019	2011-2015	Phase 3 (E-switch-ic)	mGemOx	Inconclusive whether non-inferior OS
Morizane et al. 2019 (FUGA-BT)	2013-2016	Phase 3 (C)	Gemcitabine & S-1	Seems to have non-inferior OS

Note: In ABC-02, 149 of 410 enrolled patients (36%) had primary gallbladder cancer. In FUGA-BT, 137 of 354 enrolled patients (39%) had primary gallbladder cancer.

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 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 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
Sharma A, Kalyan Mohanti B, Pal Chaudhary S, Sreenivas V, Kumar Sahoo R, Kumar Shukla N, Thulkar S, Pal S, Deo SV, Pathy S, Ranjan Dash N, Kumar S, Bhatnagar S, Kumar R, Mishra S, Sahni P, Iyer VK, Raina V. Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: Results of a phase III randomised controlled trial. Eur J Cancer. 2019 Dec;123:162-170. Epub 2019 Nov 14. link to original article contains dosing details in manuscript PubMed CTRI/2010/091/001406

Cisplatin & Gemcitabine (GC) & nab-Paclitaxel

Regimen

Study	Dates of enrollment	Evidence
Shroff et al. 2019 (MDACC 2014-0524)	2015-2017	Phase 2

Note: Prolonged median PFS and OS vs reported for historical controls treated with gemcitabine-cisplatin alone. 13 of 60 patients (22%) had primary gallbladder cancer.

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 link to PMC article contains dosing details in abstract PubMed NCT02392637

ECF

ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Rao et al. 2005	1997-2003	Phase 3 (E-switch-ic)	FELV	Did not meet primary endpoint of OS

Note: 26 of 114 enrolled patients (23%) had primary gallbladder cancer.

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 dosing details in manuscript link to PMC article PubMed

Erlotinib & Bevacizumab

Regimen

Study	Dates of enrollment	Evidence
Lubner et al. 2010 (MC044G)	2006-08 to 2008-04	Phase 2

Note: 10 of 54 patients (19%) included in endpoint analysis had primary gallbladder cancer.

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

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Rao et al. 2005	1997-2003	Phase 3 (C)	ECF	Did not meet primary endpoint of OS

Note: 26 of 54 enrolled patients (48%) had primary gallbladder cancer.

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
Leucovorin (Folinic acid) 60 mg/m² IV bolus once per day on days 1 to 3, given third

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 dosing details in manuscript link to PMC article PubMed

FULV & Gemcitabine

FULV & Gemcitabine: 5-FU, LeucoVorin, Gemcitabine

Regimen

Study	Evidence
Gebbia et al. 2001	Phase 2

Note: 22 of 40 enrolled patients (55%) had primary gallbladder cancer.

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)	GC	Inferior OS

Note: 149 of 410 enrolled patients (36%) had primary gallbladder cancer.

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 2

Note: 22 of 40 enrolled patients (55%) had primary gallbladder cancer.

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, 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)

Note: Approximately 1/3 of the patients enrolled had gallbladder cancer.

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

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)

Note: 14 of 51 enrolled patients (27%) had primary gallbladder cancer.

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 & 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)

Note: 137 of 354 enrolled patients (39%) had primary gallbladder cancer.

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
- 1.25 m² up to 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

GemOx

GemOx: Gemcitabine & Oxaliplatin
mGEMOX: modified GEMcitabine & OXaliplatin

Regimen variant #1, 900/80 ("mGEMOX")

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sharma et al. 2010	2006-2008	Randomized (E-esc)	1. Best supportive care	Superior OS (co-primary endpoint) Median OS: 9.5 vs 4.5 mo (HR 0.44, 95% CI 0.22-0.86)
Sharma et al. 2010	2006-2008	Randomized (E-esc)	2. FUFA	Not reported
Sharma et al. 2019	2011-2015	Phase 3 (E-switch-ic)	CisGem	Inconclusive whether non-inferior OS

Note: All patients enrolled in these studies had primary gallbladder cancer

Chemotherapy

Gemcitabine (Gemzar) 900 mg/m² IV once per day on days 1 & 8
Oxaliplatin (Eloxatin) 80 mg/m² IV once per day on days 1 & 8

21-day cycle for up to 6 cycles

Regimen variant #2, 1000/100, 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)	E-GEMOX	Might have inferior PFS Median PFS: 4.2 vs 5.8 mo (HR 1.25, 95% CI 0.97-1.64)

Note: 82 of 268 enrolled patients (31%) had primary gallbladder cancer

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	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kim et al. 2019 (SMC 2011-05-070)	2011-2016	Phase 3 (C)	XELOX	Non-inferior PFS

Note: 61 of 222 enrolled patients (22%) had primary gallbladder cancer.

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, 1000/85, bi-weekly

Study	Dates of enrollment	Evidence	Efficacy
Halim et al. 2010	2005-12 to 2009-11	Phase 2	ORR: 27.5%

Note: 14 of 40 enrolled patients (35%) had primary gallbladder cancer

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 #5, 1000/100 ("GEMOX-3")

Study	Evidence	Efficacy
Harder et al. 2006	Phase 2	ORR: 26% (95% CI 14–44)

GEMOX-3: GEMcitabine & OXaliplatin, 3 visits per month

Note: 10 of 31 enrolled patients (32%) had primary gallbladder cancer.

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
Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, Raina V, Shukla NK, Thulkar S, Garg P, Chaudhary SP. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol. 2010 Oct 20;28(30):4581-6. Epub 2010 Sep 20. link to original article contains dosing details in abstract 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
Sharma A, Kalyan Mohanti B, Pal Chaudhary S, Sreenivas V, Kumar Sahoo R, Kumar Shukla N, Thulkar S, Pal S, Deo SV, Pathy S, Ranjan Dash N, Kumar S, Bhatnagar S, Kumar R, Mishra S, Sahni P, Iyer VK, Raina V. Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: Results of a phase III randomised controlled trial. Eur J Cancer. 2019 Dec;123:162-170. Epub 2019 Nov 14. link to original article contains dosing details in manuscript PubMed CTRI/2010/091/001406

GEMOX-B

GEMOX-B: GEMcitabine, OXaliplatin, Bevacizumab

Regimen

Study	Evidence
Zhu et al. 2009 (MGH 05-349)	Phase 2

Note: 10 of 35 enrolled patients (29%) had primary gallbladder cancer.

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

Irinotecan monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ramaswami et al. 2020 (GB-SELECT)	2018-2020	Randomized Phase 2 (C)	Capecitabine & Irinotecan	Did not meet primary endpoint of OS6

Prior treatment criteria

Progression after prior gemcitabine-based chemotherapy

Chemotherapy

Irinotecan (Camptosar) 240 mg/m² IV bolus once on day 1

21-day cycles

References

GB-SELECT: Ramaswamy A, Ostwal V, Sharma A, Bhargava P, Srinivas S, Goel M, Patkar S, Mandavkar S, Jadhav P, Parulekar M, Choudhari A, Gupta S. Efficacy of Capecitabine Plus Irinotecan vs Irinotecan Monotherapy as Second-line Treatment in Patients With Advanced Gallbladder Cancer: A Multicenter Phase 2 Randomized Clinical Trial (GB-SELECT). JAMA Oncol. 2021 Mar 1;7(3):436-439. Epub 2020 Dec 3. link to original article contains dosing details in manuscript link to PMC article PubMed CTRI/2017/10/010112

Regorafenib monotherapy

Regimen

Study	Evidence
Sun et al. 2019 (UPMC 13-100)	Phase 2

Note: 5 of 43 enrolled patients (12%) had primary gallbladder cancer.

Prior treatment criteria

Failure of 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

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

Metastatic disease, second-line

FULV

FULV: 5-FU & LeucoVorin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Yoo et al. 2021 (NIFTY)	2018-09-05 to 2020-02-18	Randomized Phase 2b (C)	FULV & nanoliposomal Irinotecan	Inferior PFS

Chemotherapy

Fluorouracil (5-FU) 2400 mg/m² IV continuous infusion over 46 hours, started on day 1
Leucovorin (Folinic acid) 400 mg/m² IV over 30 minutes once on day 1

14-day cycles

References

NIFTY: Yoo C, Kim KP, Jeong JH, Kim I, Kang MJ, Cheon J, Kang BW, Ryu H, Lee JS, Kim KW, Abou-Alfa GK, Ryoo BY. Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study. Lancet Oncol. 2021 Nov;22(11):1560-1572. Epub 2021 Oct 14. link to original article contains dosing details in manuscript PubMed NCT03524508

FULV & nanoliposomal Irinotecan

FULV & nanoliposomal Irinotecan: 5-FU, LeucoVorin, nanoliposomal Irinotecan

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Yoo et al. 2021 (NIFTY)	2018-09-05 to 2020-02-18	Randomized Phase 2b (E-esc)	FULV	Superior PFS (primary endpoint) Median PFS: 7.1 vs 1.4 mo (HR 0.56, 95% CI 0.39-0.81) Seems to have superior OS (secondary endpoint) Median OS: 8.6 vs 5.5 mo (sHR 0.68, 95% CI 0.48-0.98)

Chemotherapy

Fluorouracil (5-FU) 2400 mg/m² IV continuous infusion over 46 hours, started on day 1
Leucovorin (Folinic acid) 400 mg/m² IV over 30 minutes once on day 1
Irinotecan liposome (Onivyde) 70 mg/m² IV over 90 minutes once on day 1, given first

14-day cycles

References

NIFTY: Yoo C, Kim KP, Jeong JH, Kim I, Kang MJ, Cheon J, Kang BW, Ryu H, Lee JS, Kim KW, Abou-Alfa GK, Ryoo BY. Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study. Lancet Oncol. 2021 Nov;22(11):1560-1572. Epub 2021 Oct 14. link to original article contains dosing details in manuscript PubMed NCT03524508

@@ Line 1: / Line 1: @@
-{| class="wikitable" style="text-align:center; width:100%;"
+<span id="BackToTop"></span>
-! colspan="2" style="color:white; font-size:125%; background-color:#08519c" align="center" |'''Page editor'''
+<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
-! colspan="2" style="color:white; font-size:125%; background-color:#08519c" align="center" |'''Section editor'''
+[[#top|Back to Top]]
-|-
+</div>
-| style="background-color:#F0F0F0; width:15%" |[[File:Seifter.jpg|frameless|upright=0.3|center]]
+{{#lst:Editorial board transclusions|gbc}}
-| style="width:35%" |<big>Ari Seifter, MD<br>University of Illinois at Chicago<br>Chicago, IL</big>
-| style="background-color:#F0F0F0; width:15%" |[[File:nkv.jpg|frameless|upright=0.3|center]]
-| style="width:35%" |<big>[[User:Neetavenepalli|Neeta K. Venepalli, MD, MBA]]<br>University of Illinois at Chicago<br>Chicago, IL</big>
-|-
-|}
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 14: / Line 9: @@
 <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 |}
-<big>Note: there is some overlap, especially in the earlier literature, between treatment regimens for gallbladder cancer and those for '''[[pancreatic cancer|pancreatic adenocarcinoma]]''', '''[[periampullary adenocarcinoma]]''', and '''[[cholangiocarcinoma]]; please see those pages for additional regimens.'''</big>
+<big>Note: there is some overlap, especially in the earlier literature, between treatment regimens for gallbladder cancer and those for '''[[pancreatic cancer|pancreatic adenocarcinoma]]''', '''[[periampullary adenocarcinoma]]''', and '''[[cholangiocarcinoma]]; please see those pages for additional regimens.'''</big><br>
+''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Gallbladder cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''
 {{TOC limit|limit=3}}
 =Guidelines=
-==[http://www.esmo.org/ ESMO]==
+'''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.'''
+==[https://www.esmo.org/ ESMO]==
+*'''2022:''' Vogel et al. [https://doi.org/10.1016/j.annonc.2022.10.506 Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/36372281 PubMed]
-*'''2016:''' Valle et al. [https://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Biliary-Cancer Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
+*'''2016:''' Valle et al. [https://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Biliary-Cancer Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/27664259 PubMed]
+==NCCN==
-==[https://www.nccn.org/ NCCN]==
+*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1517 NCCN Guidelines - Biliary Tract Cancers].''
-*[https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf NCCN Guidelines - Hepatobiliary Cancers]
 =Adjuvant therapy=
 ==Capecitabine monotherapy {{#subobject:f4c3d9|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:3a3bdf|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! 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.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30915-X/fulltext Primrose et al. 2019 (BILCAP)]
+|[https://doi.org/10.1016/S1470-2045(18)30915-X Primrose et al. 2019 (BILCAP)]
 |2006-2014
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[#Observation|Observation]]
-| style="background-color:#d9ef8b" |Might have superior OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup><br>Median OS: 49.6 vs 36.1 mo<br>(aHR 0.84, 95% CI 0.67-1.06)
 |}
+''<sup>1</sup>Reported efficacy is based on the 2022 update.''<br>
 ''79 of 447 enrolled patients (17.7%) had primary gallbladder cancer.''
 ''Note: Chemotherapy start date 8-16 weeks after surgery.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
+*[[Surgery#Surgical_resection|Surgical resection]] with macroscopically curative resection
-*[[Surgery|Surgical resection]] with macroscopically curative resection
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 '''21-day cycle for 8 cycles'''
+</div></div>
 ===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. [https://doi.org/10.1016/S1470-2045(18)30915-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/30922733/ PubMed] [https://clinicaltrials.gov/study/NCT00363584 NCT00363584]
-#'''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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30915-X/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/30922733 PubMed]
+##'''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. [https://doi.org/10.1200/jco.21.02568 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35316080/ PubMed]
-<br />
 ==Capecitabine & Gemcitabine {{#subobject:17f9f2|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 GemCap: '''<u>Gem</u>'''citabine & '''<u>Cap</u>'''ecitabine
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:e6a3e3|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 33%"|Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534524/ Ben-Josef et al. 2015 (SWOG S0809)]
-| style="background-color:#91cf61" |Phase II
+|2008-2012
+| style="background-color:#91cf61" |Phase 2
 |-
 |}
 ''25 of 79 enrolled patients (32%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Surgical_resection|Surgical resection]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Capecitabine (Xeloda)]] 750 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*[[Capecitabine (Xeloda)]] 750 mg/m<sup>2</sup>/day PO twice per day on days 1 to 14
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 '''21-day cycle for 4 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
+*Adjuvant [[#Capecitabine_.26_RT|Capecitabine & RT]]
-*Capecitabine & RT
+</div></div>
+===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. [https://doi.org/10.1200/JCO.2014.60.2219 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534524/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25964250/ PubMed] [https://clinicaltrials.gov/study/NCT00789958 NCT00789958]
+==Capecitabine & RT {{#subobject:xrt9f2|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:e15re3|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534524/ Ben-Josef et al. 2015 (SWOG S0809)]
+|2008-2012
+| style="background-color:#91cf61" |Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e7">
+====Preceding treatment====
+*Adjuvant [[#Capecitabine_.26_Gemcitabine|GemCap]] x 4
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Capecitabine (Xeloda)]] 665 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+====Radiotherapy====
+*Concurrent [[External_beam_radiotherapy|radiation therapy]] 5400 cGy in 30 fractions, given 5 times per week
+'''40-day course'''
+</div></div>
 ===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. [https://doi.org/10.1200/JCO.2014.60.2219 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534524/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25964250/ PubMed] [https://clinicaltrials.gov/study/NCT00789958 NCT00789958]
-#'''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. [https://doi.org/10.1200/JCO.2014.60.2219 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534524/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25964250 PubMed]
 ==GemOx {{#subobject:f8c8d9|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 GemOx: '''<u>Gem</u>'''citabine & '''<u>Ox</u>'''aliplatin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:3ghg3f|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 113: / Line 124: @@
 |[https://doi.org/10.1200/JCO.18.00050 Edeline et al. 2019 (PRODIGE 12-ACCORD 18-UNICANCER GI)]
 |2009-2014
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[#Observation|Observation]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 |}
 ''38 of 194 enrolled patients (20%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
+*[[Surgery#Surgical_resection|Surgical resection]] with macroscopically curative resection
-*[[Surgery|Surgical resection]] with macroscopically curative resection
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once on day 1
 *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 2
 '''14-day cycle for 12 cycles'''
+</div></div>
 ===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. [https://doi.org/10.1200/JCO.18.00050 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30707660/ PubMed] [https://clinicaltrials.gov/study/NCT01313377 NCT01313377]
-#'''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. [https://doi.org/10.1200/JCO.18.00050 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30707660 PubMed]
+==S-1 monotherapy {{#subobject:252c51|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:cdcc15|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://doi.org/10.1016/s0140-6736(22)02038-4 Nakachi et al 2023 (ASCOT)]
+|2013-09-09 to 2018-06-22
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Gallbladder cancer - null regimens#Observation|Observation]]
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>OS36: 77.1% vs 67.6%<br>(HR 0.69, 95% CI 0.51-0.94)
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Surgical_resection|Surgical resection]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Tegafur, gimeracil, oteracil (S-1)]] by the following BSA-based criteria:
+**Less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28
+**1.25 m<sup>2</sup> up to 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 28
+**1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 28
+'''42-day cycle for up to 4 cycles'''
+</div></div>
+===References===
+#'''ASCOT:''' Nakachi K, Ikeda M, Konishi M, Nomura S, Katayama H, Kataoka T, Todaka A, Yanagimoto H, Morinaga S, Kobayashi S, Shimada K, Takahashi Y, Nakagohri T, Gotoh K, Kamata K, Shimizu Y, Ueno M, Ishii H, Okusaka T, Furuse J; Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG). Adjuvant S-1 compared with observation in resected biliary tract cancer (JCOG1202, ASCOT): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet. 2023 Jan 21;401(10372):195-203. PMID: 36681415. [https://doi.org/10.1016/s0140-6736(22)02038-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36681415/ PubMed] UMIN000011688
 =Metastatic or unresectable disease, all lines of therapy=
 ==Capecitabine monotherapy {{#subobject:c7cfeb|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:b34ea|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 50%" |Study
 ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://onlinelibrary.wiley.com/doi/10.1002/cncr.20368/full Patt et al. 2004]
+|[https://doi.org/10.1002/cncr.20368 Patt et al. 2004]
 | style="background-color:#ffffbe" |Retrospective
 |-
 |}
-''3 of 37 patients (8%) had primary gallbladder cancer.''
+''Note: 3 of 37 patients (8%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 '''21-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1002/cncr.20368 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15274071/ PubMed]
-#'''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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.20368/full link to original article] [https://pubmed.ncbi.nlm.nih.gov/15274071 PubMed]
+==CAPIRI {{#subobject:6a9270|Regimen=1}}==
+CAPIRI: '''<u>CAP</u>'''ecitabine & '''<u>IRI</u>'''notecan
+<div class="toccolours" style="background-color:#eeeeee">
-==Capecitabine & Irinotecan {{#subobject:6a9270|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:a46bbd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! 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://pubmed.ncbi.nlm.nih.gov/33270098/ Ramaswami et al. 2020 (GB-SELECT)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716253/ Ramaswami et al. 2020 (GB-SELECT)]
 |2018-2020
-| style="background-color:#1a9851" |Randomized Phase II (E-switch-ic)
+| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
-|[[#Gemcitabine .26 Mitomycin|Irinotecan Monotherapy]]
+|[[Gallbladder cancer#Irinotecan monotherapy|Irinotecan]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS6
 |-
 |}
-''All patients had progressed after prior gemcitabine-based chemothearpy''
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*Progression after prior gemcitabine-based chemotherapy
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Capecitabine (Xeloda)]] 1700 mg/m<sup>2</sup>/day PO on days 1 to 14
-*[[Capecitabine (Xeloda)]] 1700 mg/m<sup><font size="2">2</font></sup> PO daily on days 1 to 14
+*[[Irinotecan (Camptosar)]] 200 mg/m<sup>2</sup> IV bolus once on day 1
-*[[Irinotecan (Camptosar)]] 8 mg/m<sup><font size="2">2</font></sup> IV bolus once on day 1
 '''21-day cycles'''
+</div></div>
 ===References===
+#'''GB-SELECT:''' Ramaswamy A, Ostwal V, Sharma A, Bhargava P, Srinivas S, Goel M, Patkar S, Mandavkar S, Jadhav P, Parulekar M, Choudhari A, Gupta S. Efficacy of Capecitabine Plus Irinotecan vs Irinotecan Monotherapy as Second-line Treatment in Patients With Advanced Gallbladder Cancer: A Multicenter Phase 2 Randomized Clinical Trial (GB-SELECT). JAMA Oncol. 2021 Mar 1;7(3):436-439. Epub 2020 Dec 3. [https://doi.org/10.1001/jamaoncol.2020.6166 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716253/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33270098/ PubMed] CTRI/2017/10/010112
-#Ramaswamy A, Ostwal V, Sharma A, et al. Efficacy of Capecitabine Plus Irinotecan vs Irinotecan Monotherapy as Second-line Treatment in Patients With Advanced Gallbladder Cancer: A Multicenter Phase 2 Randomized Clinical Trial (GB-SELECT). JAMA Oncol. Published online December 03, 2020. doi:10.1001/jamaoncol.2020.6166 [https://jamanetwork.com/journals/jamaoncology/article-abstract/2773377 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33270098/ PubMed]
 ==Capecitabine & Mitomycin {{#subobject:6a9270|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:a46bbd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 208: / Line 235: @@
 |[https://doi.org/10.1093/annonc/mdh096 Kornek et al. 2004]
 |2000-2001
-| style="background-color:#1a9851" |Randomized Phase II (E-switch-ic)
+| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
-|[[#Gemcitabine .26 Mitomycin|Gemcitabine & Mitomycin]]
+|[[#Gemcitabine_.26_Mitomycin|Gemcitabine & Mitomycin]]
-| style="background-color:#d9ef8b" |Might have superior ORR
+| style="background-color:#d9ef8b" |Might have superior ORR (primary endpoint)
 |-
 |}
-''14 of 51 enrolled patients (27%) had primary gallbladder cancer.''
+''Note: 14 of 51 enrolled patients (27%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*[[Capecitabine (Xeloda)]] 1000 mg/m<sup><font size="2">2</font></sup> PO twice per day on days 1 to 14
+*[[Mitomycin (Mutamycin)]] 8 mg/m<sup>2</sup> IV bolus once on day 1
-*[[Mitomycin (Mutamycin)]] 8 mg/m<sup><font size="2">2</font></sup> IV bolus once on day 1
+====Supportive therapy====
-====Supportive medications====
 *[[Dexamethasone (Decadron)]] and [[:Category:Serotonin 5-HT3 antagonists|5-HT3 antagonists]] on the day of IV chemotherapy
 '''28-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1093/annonc/mdh096 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14998852/ PubMed]
-#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. [https://doi.org/10.1093/annonc/mdh096 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/14998852 PubMed]
 ==CapeOx {{#subobject:cf9acc|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 CapeOx: '''<u>Cape</u>'''citabine & '''<u>Ox</u>'''aliplatin
 <br>XELOX: '''<u>XEL</u>'''oda (Capecitabine) & '''<u>OX</u>'''aliplatin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:1ef938|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 246: / Line 265: @@
 |[https://doi.org/10.1093/annonc/mdz058 Kim et al. 2019 (SMC 2011-05-070)]
 |2011-2016
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 |[[#GemOx_2|GEMOX]]
-| style="background-color:#eeee01" |Non-inferior PFS
+| style="background-color:#eeee01" |Non-inferior PFS6<br>PFS6: 46.7% vs 44.5%
 |-
 |}
-''61 of 222 enrolled patients (22%) had primary gallbladder cancer.''
+''Note: 61 of 222 enrolled patients (22%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
 '''21-day cycle for 8 cycles'''
+</div></div>
 ===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 protocol''' [https://pubmed.ncbi.nlm.nih.gov/30785198 PubMed]
+==Cisplatin & Gemcitabine (GC) {{#subobject:af0357|Regimen=1}}==
-==Cisplatin & Gemcitabine {{#subobject:af0357|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''isplatin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:cb3c9d|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! 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.nejm.org/doi/full/10.1056/NEJMoa0908721 Valle et al. 2010 (ABC-02)]
+|[https://doi.org/10.1056/NEJMoa0908721 Valle et al. 2010 (ABC-02)]
 |2002-2008
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[#Gemcitabine monotherapy 2|Gemcitabine]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#1a9850" |Superior OS (primary endpoint)
 |-
 |[https://doi.org/10.1016/j.ejca.2019.10.004 Sharma et al. 2019]
 |2011-2015
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 |[[#GemOx|mGemOx]]
 | style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
@@ Line 292: / Line 305: @@
 |[https://doi.org/10.1093/annonc/mdz402 Morizane et al. 2019 (FUGA-BT)]
 |2013-2016
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Gemcitabine .26 S-1|Gemcitabine & S-1]]
+|[[#Gemcitabine_.26_S-1|Gemcitabine & S-1]]
 | style="background-color:#eeee01" |Seems to have non-inferior OS
 |-
 |}
-''In ABC-02, 149 of 410 enrolled patients (36%) had primary gallbladder cancer.''
+''Note: In ABC-02, 149 of 410 enrolled patients (36%) had primary gallbladder cancer. In FUGA-BT, 137 of 354 enrolled patients (39%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
-''In FUGA-BT, 137 of 354 enrolled patients (39%) had primary gallbladder cancer.''
 ====Chemotherapy====
+*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8, '''given first'''
-*[[Cisplatin (Platinol)]] 25 mg/m<sup><font size="2">2</font></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'''
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup><font size="2">2</font></sup> IV over 30 minutes once per day on days 1 & 8, '''given second'''
+====Supportive therapy====
-====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'''
+</div></div>
 ===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]
-#'''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://www.nejm.org/doi/full/10.1056/NEJMoa0908721 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20375404 PubMed]
+#'''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
-#'''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. [https://doi.org/10.1093/annonc/mdz402 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31566666 PubMed]
+#Sharma A, Kalyan Mohanti B, Pal Chaudhary S, Sreenivas V, Kumar Sahoo R, Kumar Shukla N, Thulkar S, Pal S, Deo SV, Pathy S, Ranjan Dash N, Kumar S, Bhatnagar S, Kumar R, Mishra S, Sahni P, Iyer VK, Raina V. Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: Results of a phase III randomised controlled trial. Eur J Cancer. 2019 Dec;123:162-170. Epub 2019 Nov 14. [https://doi.org/10.1016/j.ejca.2019.10.004 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31707181/ PubMed] CTRI/2010/091/001406
-#Sharma A, Kalyan Mohanti B, Pal Chaudhary S, Sreenivas V, Kumar Sahoo R, Kumar Shukla N, Thulkar S, Pal S, Deo SV, Pathy S, Ranjan Dash N, Kumar S, Bhatnagar S, Kumar R, Mishra S, Sahni P, Iyer VK, Raina V. Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: Results of a phase III randomised controlled trial. Eur J Cancer. 2019 Dec;123:162-170. Epub 2019 Nov 14. [https://doi.org/10.1016/j.ejca.2019.10.004 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/31707181 PubMed] CTRI/2010/091/001406
+==Cisplatin & Gemcitabine (GC) & nab-Paclitaxel {{#subobject:17f9f2|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-==Cisplatin, Gemcitabine, nab-Paclitaxel {{#subobject:17f9f2|Regimen=1}}==
+===Regimen {{#subobject:e6a3e3|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[[#top|back to top]]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6567834/ Shroff et al. 2019 (MDACC 2014-0524)]
+|2015-2017
+| style="background-color:#91cf61" |Phase 2
 |}
-===Regimen {{#subobject:e6a3e3|Variant=1}}===
+''Note: Prolonged median PFS and OS vs reported for historical controls treated with gemcitabine-cisplatin alone. 13 of 60 patients (22%) had primary gallbladder cancer.''
-{| class="wikitable" style="width: 50%; text-align:center;"
+<div class="toccolours" style="background-color:#b3e2cd">
-! style="width: 50%" |Study
-! style="width: 50%" |[[Levels of Evidence#Evidence|Evidence]]
-|-
-|[https://jamanetwork.com/journals/jamaoncology/article-abstract/2730639 Shroff et al. 2019 (MDACC 2014-0524)]
-| style="background-color:#91cf61" |Phase II
-|}''Prolonged median PFS and OS vs reported for historical controls treated with gemcitabine-cisplatin alone.''
-''13 of 60 patients (22%) had  primary gallbladder cancer.''
 ====Chemotherapy====
+*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8
-*[[Cisplatin (Platinol)]] 25 mg/m<sup><font size="2">2</font></sup> IV over 60 minutes once per day on days 1 & 8
+*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Gemcitabine (Gemzar)]] 800 mg/m<sup><font size="2">2</font></sup> IV once per day on days 1 & 8
+*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 100 mg/m<sup><font size="2">2</font></sup> IV once per day on days 1 & 8
+'''21-day cycles'''
+</div></div>
-'''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 Jun 1;5(6):824-830. Epub 2019 Apr 18. [https://jamanetwork.com/journals/jamaoncology/article-abstract/2730639 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6567834/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30998813/ PubMed] [https://clinicaltrials.gov/study/NCT02392637 NCT02392637]
-#'''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] [https://jamanetwork.com/journals/jamaoncology/article-abstract/2730639 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30998813 PubMed]
 ==ECF {{#subobject:57bd6d|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:f87869|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 361: / Line 360: @@
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362051/ Rao et al. 2005]
 |1997-2003
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 |[[#FELV|FELV]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-''26 of 114 enrolled patients (23%) had primary gallbladder cancer.''
+''Note: 26 of 114 enrolled patients (23%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Epirubicin (Ellence)]] 50 mg/m<sup><font size="2">2</font></sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Cisplatin (Platinol)]] 60 mg/m<sup><font size="2">2</font></sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4200 mg/m<sup>2</sup>)
-*[[Fluorouracil (5-FU)]] 200 mg/m<sup><font size="2">2</font></sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4200 mg/m<sup><font size="2">2</font></sup>)
 '''21-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1038/sj.bjc.6602576 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362051/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15856037/ PubMed]
-#Rao S, Cunningham D, Hawkins RE, Hill ME, Smith D, Daniel F, Ross PJ, Oates J, Norman AR. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer. Br J Cancer. 2005 May 9;92(9):1650-4. [https://doi.org/10.1038/sj.bjc.6602576 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362051/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15856037 PubMed]
 ==Erlotinib & Bevacizumab {{#subobject:CMR1|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:CMV1|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 33%"|Study
-! style="width: 50%" |[[Levels of Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917213/ Lubner et al. 2010]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917213/ Lubner et al. 2010 (MC044G)]
-| style="background-color:#91cf61" |Phase II
+|2006-08 to 2008-04
+| style="background-color:#91cf61" |Phase 2
 |-
 |}
-''10 of 54 patients (19%) included in endpoint analysis had primary gallbladder cancer.''
+''Note: 10 of 54 patients (19%) included in endpoint analysis had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
+*[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 28
-*[[Erlotinib (Tarceva)]] 150 mg PO once per day
 *[[Bevacizumab (Avastin)]] 5 mg/kg IV once per day on days 1 & 15
+'''28-day cycles'''
+</div></div>
-'''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. [https://doi.org/10.1200/jco.2010.28.4075 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917213/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20530271/ PubMed] [https://clinicaltrials.gov/study/NCT00356889 NCT00356889]
-#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. [http://jco.ascopubs.org/content/28/21/3491.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917213/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20530271 PubMed]
 ==FELV {{#subobject:3658a8|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+FELV: '''<u>F</u>'''luorouracil , '''<u>E</u>'''toposide, '''<u>L</u>'''euco'''<u>V</u>'''orin
-|-
+<div class="toccolours" style="background-color:#eeeeee">
-|[[#top|back to top]]
-|}
-FELV: '''<u>F</u>'''luorouracil , '''<u>E</u>'''toposide, '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid)
 ===Regimen {{#subobject:8e152d|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 423: / Line 411: @@
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362051/ Rao et al. 2005]
 |1997-2003
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
 |[[#ECF|ECF]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-''26 of 54 enrolled patients (48%) had primary gallbladder cancer.''
+''Note: 26 of 54 enrolled patients (48%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3, '''given first'''
-*[[Fluorouracil (5-FU)]] 600 mg/m<sup><font size="2">2</font></sup> IV bolus once per day on days 1 to 3, '''given first'''
+*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV over 40 minutes once per day on days 1 to 3, '''given second'''
-*[[Etoposide (Vepesid)]] 120 mg/m<sup><font size="2">2</font></sup> IV over 40 minutes once per day on days 1 to 3, '''given second'''
+*[[Leucovorin (Folinic acid)]] 60 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3, '''given third'''
-*[[Folinic acid (Leucovorin)]] 60 mg/m<sup><font size="2">2</font></sup> IV bolus once per day on days 1 to 3, '''given third'''
 '''21-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1038/sj.bjc.6602576 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362051/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15856037/ PubMed]
-#Rao S, Cunningham D, Hawkins RE, Hill ME, Smith D, Daniel F, Ross PJ, Oates J, Norman AR. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer. Br J Cancer. 2005 May 9;92(9):1650-4. [https://doi.org/10.1038/sj.bjc.6602576 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362051/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15856037 PubMed]
 ==FULV & Gemcitabine {{#subobject:eb427f|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+FULV & Gemcitabine: 5-'''<u>FU</u>''', '''<u>L</u>'''euco'''<u>V</u>'''orin, Gemcitabine
-|-
+<div class="toccolours" style="background-color:#eeeeee">
-|[[#top|back to top]]
-|}
-FULV & Gemcitabine: 5-'''<u>FU</u>''', '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid), Gemcitabine
 ===Regimen {{#subobject:85fb7b|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 50%" |Study
 ! style="width: 50%" |[[Levels of Evidence#Evidence|Evidence]]
 |-
-|[http://jco.ascopubs.org/content/19/20/4089.2.long Gebbia et al. 2001]
+|[https://doi.org/10.1200/jco.2001.19.20.4089 Gebbia et al. 2001]
-| style="background-color:#91cf61" |Phase II
+| style="background-color:#91cf61" |Phase 2
 |-
 |}
-''22 of 40 enrolled patients (55%) had primary gallbladder cancer.''
+''Note: 22 of 40 enrolled patients (55%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours (total dose per cycle: 1000 mg/m<sup>2</sup>)
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup><font size="2">2</font></sup> IV bolus once on day 1, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours (total dose per cycle: 1000 mg/m<sup>2</sup>)
+*[[Leucovorin (Folinic acid)]] 100 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Folinic acid (Leucovorin)]] 100 mg/m<sup><font size="2">2</font></sup> IV over 2 hours once on day 1
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup><font size="2">2</font></sup> IV once per day on days 1 & 8
 '''21-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1200/jco.2001.19.20.4089 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11600613/ PubMed]
-#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. [http://jco.ascopubs.org/content/19/20/4089.2.long link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/11600613 PubMed]
 ==Gemcitabine monotherapy {{#subobject:1129f1|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen variant #1 {{#subobject:b0f450|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! 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.nejm.org/doi/full/10.1056/NEJMoa0908721 Valle et al. 2010 (ABC-02)]
+|[https://doi.org/10.1056/NEJMoa0908721 Valle et al. 2010 (ABC-02)]
 |2002-2008
-| style="background-color:#1a9851" |Phase III (E-de-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin .26 Gemcitabine|Cisplatin & Gemcitabine]]
+|[[#Cisplatin_.26_Gemcitabine_.28GC.29|GC]]
 | style="background-color:#d73027" |Inferior OS
 |-
 |}
-''149 of 410 enrolled patients (36%) had primary gallbladder cancer.''
+''Note: 149 of 410 enrolled patients (36%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup><font size="2">2</font></sup> IV over 30 minutes once per day on days 1, 8, 15
 '''28-day cycle for 3 to 6 cycles depending on response'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2 {{#subobject:fcd6f1|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 50%" |Study
 ! style="width: 50%" |[[Levels of Evidence#Evidence|Evidence]]
 |-
-|[http://jco.ascopubs.org/content/19/20/4089.2.long Gebbia et al. 2001]
+|[https://doi.org/10.1200/jco.2001.19.20.4089 Gebbia et al. 2001]
-| style="background-color:#91cf61" |Phase II
+| style="background-color:#91cf61" |Phase 2
 |-
 |}
-''22 of 40 enrolled patients (55%) had primary gallbladder cancer.''
+''Note: 22 of 40 enrolled patients (55%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup><font size="2">2</font></sup> IV over 30 minutes once per day on days 1, 8, 15
 '''30-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1200/jco.2001.19.20.4089 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11600613/ PubMed]
-#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. [http://jco.ascopubs.org/content/19/20/4089.2.long link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/11600613 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. [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]
-#'''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://www.nejm.org/doi/full/10.1056/NEJMoa0908721 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20375404 PubMed]
 ==Gemcitabine, Cisplatin, S-1 {{#subobject:e0d17a|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 GCS: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin, '''<u>S</u>'''-1
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:87f9c7|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! 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://academic.oup.com/annonc/article/29/suppl_8/mdy282/5140253 Sakai et al. 2018 (KHBO1401-MITSUBA)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10086809/ Ioka et al. 2022 (KHBO1401-MITSUBA)]
-|2014-NR
+|2014-2016
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Cisplatin .26 Gemcitabine|Cisplatin & Gemcitabine]]
+|[[#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]]
-| style="background-color:#d9ef8b" |Seems to have superior OS
+| style="background-color:#d9ef8b" |Might have superior OS (primary endpoint)<br>Median OS: 13.5 vs 12.6 mo<br>(HR 0.79, 90% CI 0.63-0.996)
+|-
 |}
-''Although patients with primary gallbladder cancer met eligibility criteria, the relative number of patients enrolled was not reported in the presented abstract.''
+''Note: Approximately 1/3 of the patients enrolled had gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once on day 1
-*[[Cisplatin (Platinol)]] 25 mg/m<sup><font size="2">2</font></sup> IV once on day 1
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once on day 1
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup><font size="2">2</font></sup> IV once on day 1
+*[[Tegafur, gimeracil, oteracil (S-1)]] 80 mg/m<sup>2</sup> PO once per day on days 1 to 7
-*[[Tegafur, gimeracil, oteracil (S-1)]] 80 mg/m<sup><font size="2">2</font></sup> PO once per day on days 1 to 7
 '''14-day cycles'''
+</div></div>
 ===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 [https://academic.oup.com/annonc/article/29/suppl_8/mdy282/5140253 link to abstract] -->
-#'''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 [https://academic.oup.com/annonc/article/29/suppl_8/mdy282/5140253 link to abstract]
+#'''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] '''contains dosing details in abstract''' [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]
 ==Gemcitabine & Mitomycin {{#subobject:5dad3c|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:42a188|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 568: / Line 532: @@
 |[https://doi.org/10.1093/annonc/mdh096 Kornek et al. 2004]
 |2000-2001
-| style="background-color:#1a9851" |Randomized Phase II (E-switch-ic)
+| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
-|[[#Capecitabine .26 Mitomycin|Capecitabine & Mitomycin]]
+|[[#Capecitabine_.26_Mitomycin|Capecitabine & Mitomycin]]
-| style="background-color:#fee08b" |Might have inferior ORR
+| style="background-color:#fee08b" |Might have inferior ORR (primary endpoint)
 |-
 |}
-''14 of 51 enrolled patients (27%) had primary gallbladder cancer.''
+''Note: 14 of 51 enrolled patients (27%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Gemcitabine (Gemzar)]] 2000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 15
-*[[Gemcitabine (Gemzar)]] 2000 mg/m<sup><font size="2">2</font></sup> IV over 30 minutes once per day on days 1 & 15
+*[[Mitomycin (Mutamycin)]] 8 mg/m<sup>2</sup> IV bolus once on day 1
-*[[Mitomycin (Mutamycin)]] 8 mg/m<sup><font size="2">2</font></sup> IV bolus once on day 1
+====Supportive therapy====
-====Supportive medications====
 *[[Dexamethasone (Decadron)]] and [[:Category:Serotonin 5-HT3 antagonists|5-HT3 antagonists]] on the day of IV chemotherapy
 '''28-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1093/annonc/mdh096 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14998852/ PubMed]
-#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. [https://doi.org/10.1093/annonc/mdh096 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/14998852 PubMed]
 ==Gemcitabine & S-1 {{#subobject:afbc17|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 GS: '''<u>G</u>'''emcitabine & '''<u>S</u>'''-1
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:cb3b9cd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels of Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 606: / Line 561: @@
 |[https://doi.org/10.1093/annonc/mdz402 Morizane et al. 2019 (FUGA-BT)]
 |2013-2016
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Cisplatin_.26_Gemcitabine|Gemcitabine & Cisplatin]]
+|[[#Cisplatin_.26_Gemcitabine_.28GC.29|Gemcitabine & Cisplatin]]
-| style="background-color:#eeee01" |Seems to have non-inferior OS
+| style="background-color:#eeee01" |Seems to have non-inferior OS (primary endpoint)<br>Median OS: 15.1 vs 13.4 mo<br>(HR 0.945, 90% CI 0.78-1.15)
 |-
 |}
-''137 of 354 enrolled patients (39%) had primary gallbladder cancer.''
+''Note: 137 of 354 enrolled patients (39%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Gemcitabine (Gemzar)]]
+*[[Tegafur, gimeracil, oteracil (S-1)]] by the following BSA-based criteria:
-*[[Tegafur, gimeracil, oteracil (S-1)]]
+**Less than 1.25 m<sup>2</sup>: 30 mg PO twice per day on days 1 to 14
+**1.25 m<sup>2</sup> up to 1.5 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
+**1.5 m<sup>2</sup> or more: 50 mg PO twice per day on days 1 to 14
+'''21-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1093/annonc/mdz402 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31566666/ PubMed] UMIN000010667
-#'''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. [https://doi.org/10.1093/annonc/mdz402 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31566666 PubMed]
 ==GemOx {{#subobject:c7cmar|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 GemOx: '''<u>Gem</u>'''citabine & '''<u>Ox</u>'''aliplatin
 <br>mGEMOX: '''<u>m</u>'''odified '''<u>GEM</u>'''citabine & '''<u>OX</u>'''aliplatin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 900/80 ("mGEMOX") {{#subobject:b343ca|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 641: / Line 595: @@
 | rowspan="2" style="background-color:#1a9851" |Randomized (E-esc)
 |1. [[Gallbladder_cancer_-_null_regimens#Best_supportive_care|Best supportive care]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#1a9850" |Superior OS (co-primary endpoint)<br>Median OS: 9.5 vs 4.5 mo<br>(HR 0.44, 95% CI 0.22-0.86)
 |-
-|2. FUFA
+|2. [[#FULV_999|FUFA]]
 | style="background-color:#d3d3d3" |Not reported
 |-
 |[https://doi.org/10.1016/j.ejca.2019.10.004 Sharma et al. 2019]
 |2011-2015
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Cisplatin_.26_Gemcitabine|CisGem]]
+|[[#Cisplatin_.26_Gemcitabine_.28GC.29|CisGem]]
 | style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 |-
 |}
-''All patients enrolled in these studies had primary gallbladder cancer''
+''Note: All patients enrolled in these studies had primary gallbladder cancer''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] 900 mg/m<sup>2</sup> IV once per day on days 1 & 8
 *[[Oxaliplatin (Eloxatin)]] 80 mg/m<sup>2</sup> IV once per day on days 1 & 8
 '''21-day cycle for up to 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 1000/100, bi-weekly {{#subobject:c652ca|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! 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.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70301-1/fulltext Lee et al. 2011 (SMC 2008-12-024)]
+|[https://doi.org/10.1016/S1470-2045(11)70301-1 Lee et al. 2011 (SMC 2008-12-024)]
-|2009-2010
+|2009-02-16 to 2010-08-01
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|E-GEMOX
+|[[#GemOx_.26_Erlotinib_333|E-GEMOX]]
-| style="background-color:#fee08b" |Might have inferior PFS
+| style="background-color:#fee08b" |Might have inferior PFS<br>Median PFS: 4.2 vs 5.8 mo<br>(HR 1.25, 95% CI 0.97-1.64)
 |-
 |}
-''82 of 268 enrolled patients (31%) had primary gallbladder cancer''
+''Note: 82 of 268 enrolled patients (31%) had primary gallbladder cancer''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once on day 1
 *[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV once on day 2
 '''14-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 1000/100, 2 weeks out of 3 {{#subobject:a6c33cb|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 696: / Line 649: @@
 |[https://doi.org/10.1093/annonc/mdz058 Kim et al. 2019 (SMC 2011-05-070)]
 |2011-2016
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
 |[[#CapeOx|XELOX]]
 | style="background-color:#eeee01" |Non-inferior PFS
 |-
 |}
-''61 of 222 enrolled patients (22%) had primary gallbladder cancer.''
+''Note: 61 of 222 enrolled patients (22%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 *[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV once on day 1
 '''21-day cycle for 8 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #4, 1000/85, bi-weekly {{#subobject:508f1b|Variant=1}}===
-{| class="wikitable" style="width: 75%; text-align:center;"
+{| class="wikitable sortable" style="width: 80%; text-align:center;"
-! style="width: 33%" |Study
+!style="width: 25%"|Study
-! style="width: 33%" |[[Levels of Evidence#Evidence|Evidence]]
+!style="width: 25%"|Dates of enrollment
-! style="width: 33%" |[[Levels of Evidence#Efficacy|Efficacy]]
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[https://academic.oup.com/jjco/article/41/2/217/875887 Halim et al. 2011]
+|[https://academic.oup.com/jjco/article/41/2/217/875887 Halim et al. 2010]
-| style="background-color:#91cf61" |Phase II
+|2005-12 to 2009-11
+| style="background-color:#91cf61" |Phase 2
 |ORR: 27.5%
 |-
 |}
-''14 of 40 enrolled patients (35%) had primary gallbladder cancer''
+''Note: 14 of 40 enrolled patients (35%) had primary gallbladder cancer''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once on day 1, '''given first'''
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup><font size="2">2</font></sup> IV over 30 minutes once on day 1, '''given first'''
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second'''
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup><font size="2">2</font></sup> IV over 2 hours once on day 1, '''given second'''
 '''14-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #5, 1000/100 ("GEMOX-3") {{#subobject:a8fefg|Variant=1}}===
-{| class="wikitable" style="width: 75%; text-align:center;"
+{| class="wikitable" style="width: 60%; text-align:center;"
 ! style="width: 33%" |Study
 ! style="width: 33%" |[[Levels of Evidence#Evidence|Evidence]]
@@ Line 735: / Line 690: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360533/ Harder et al. 2006]
-| style="background-color:#91cf61" |Phase II
+| style="background-color:#91cf61" |Phase 2
 |ORR: 26% (95% CI 14–44)
 |-
 |}GEMOX-3: '''<u>GEM</u>'''citabine & '''<u>OX</u>'''aliplatin, 3 visits per month
+''Note: 10 of 31 enrolled patients (32%) had primary gallbladder cancer.''
-''10 of 31 enrolled patients (32%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, '''given first'''
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup><font size="2">2</font></sup> IV over 30 minutes once per day on days 1, 8, 15, '''given first'''
+*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 15, '''given second'''
-*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup><font size="2">2</font></sup> IV over 2 hours once per day on days 1 & 15, '''given second'''
 '''28-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1038/sj.bjc.6603334 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360533/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16969352/ PubMed]
-#Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, Raina V, Shukla NK, Thulkar S, Garg P, Chaudhary SP. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol. 2010 Oct 20;28(30):4581-6. Epub 2010 Sep 20. [https://doi.org/10.1200/JCO.2010.29.3605 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/20855823 PubMed]
+#Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, Raina V, Shukla NK, Thulkar S, Garg P, Chaudhary SP. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol. 2010 Oct 20;28(30):4581-6. Epub 2010 Sep 20. [https://doi.org/10.1200/JCO.2010.29.3605 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20855823/ 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70301-1/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/22192731 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. [https://academic.oup.com/jjco/article/41/2/217/875887 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21062755/ 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. [https://doi.org/10.1093/annonc/mdz058 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/30785198 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. [https://doi.org/10.1016/S1470-2045(11)70301-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22192731/ PubMed] [https://clinicaltrials.gov/study/NCT01149122 NCT01149122]
-#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. [https://academic.oup.com/jjco/article/41/2/217/875887 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/21062755 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. [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]
-#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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360533/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/16969352 PubMed]
+#Sharma A, Kalyan Mohanti B, Pal Chaudhary S, Sreenivas V, Kumar Sahoo R, Kumar Shukla N, Thulkar S, Pal S, Deo SV, Pathy S, Ranjan Dash N, Kumar S, Bhatnagar S, Kumar R, Mishra S, Sahni P, Iyer VK, Raina V. Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: Results of a phase III randomised controlled trial. Eur J Cancer. 2019 Dec;123:162-170. Epub 2019 Nov 14. [https://doi.org/10.1016/j.ejca.2019.10.004 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31707181/ PubMed] CTRI/2010/091/001406
-#Sharma A, Kalyan Mohanti B, Pal Chaudhary S, Sreenivas V, Kumar Sahoo R, Kumar Shukla N, Thulkar S, Pal S, Deo SV, Pathy S, Ranjan Dash N, Kumar S, Bhatnagar S, Kumar R, Mishra S, Sahni P, Iyer VK, Raina V. Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: Results of a phase III randomised controlled trial. Eur J Cancer. 2019 Dec;123:162-170. Epub 2019 Nov 14. [https://doi.org/10.1016/j.ejca.2019.10.004 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/31707181 PubMed] CTRI/2010/091/001406
 ==GEMOX-B {{#subobject:119bb0|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 GEMOX-B: '''<u>GEM</u>'''citabine, '''<u>OX</u>'''aliplatin, '''<u>B</u>'''evacizumab
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:3748a1|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 50%" |Study
 ! style="width: 50%" |[[Levels of Evidence#Evidence|Evidence]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970333-X/fulltext Zhu et al. 2009 (MGH 05-349)]
+|[https://doi.org/10.1016/S1470-2045%2809%2970333-X Zhu et al. 2009 (MGH 05-349)]
-| style="background-color:#91cf61" |Phase II
+| style="background-color:#91cf61" |Phase 2
 |-
 |}
-''10 of 35 enrolled patients (29%) had primary gallbladder cancer.''
+''Note: 10 of 35 enrolled patients (29%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[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><font size="2">2</font></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><font size="2">2</font></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'''
 '''28-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1016/S1470-2045%2809%2970333-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19932054/ PubMed]
-#'''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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970333-X/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/19932054 PubMed]
+<br />
+==Irinotecan monotherapy {{#subobject:6a9270|Regimen=1}}==
-==Regorafenib monotherapy {{#subobject:17f9f2|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Regimen {{#subobject:a46bbd|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/PMC7716253/ Ramaswami et al. 2020 (GB-SELECT)]
+|2018-2020
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
+|[[#CAPIRI|Capecitabine & Irinotecan]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS6
 |-
-|[[#top|back to top]]
 |}
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*Progression after prior gemcitabine-based chemotherapy
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Irinotecan (Camptosar)]] 240 mg/m<sup>2</sup> IV bolus once on day 1
+'''21-day cycles'''
+</div></div>
+===References===
+#'''GB-SELECT:''' Ramaswamy A, Ostwal V, Sharma A, Bhargava P, Srinivas S, Goel M, Patkar S, Mandavkar S, Jadhav P, Parulekar M, Choudhari A, Gupta S. Efficacy of Capecitabine Plus Irinotecan vs Irinotecan Monotherapy as Second-line Treatment in Patients With Advanced Gallbladder Cancer: A Multicenter Phase 2 Randomized Clinical Trial (GB-SELECT). JAMA Oncol. 2021 Mar 1;7(3):436-439. Epub 2020 Dec 3. [https://doi.org/10.1001/jamaoncol.2020.6166 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716253/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33270098/ PubMed] CTRI/2017/10/010112
+==Regorafenib monotherapy {{#subobject:17f9f2|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:e6a3e3|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
+{| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 50%" |Study
 ! style="width: 50%" |[[Levels of Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402964/ Sun et al. 2019]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402964/ Sun et al. 2019 (UPMC 13-100)]
-| style="background-color:#91cf61" |Phase II
+| style="background-color:#91cf61" |Phase 2
-|}''Only studied in patients with advanced biliary cancer who failed at least 1 line of systemic therapy.''
+|}
+''Note: 5 of 43 enrolled patients (12%) had primary gallbladder cancer.''
-''5 of 43 enrolled patients (12%) had primary gallbladder cancer.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*Failure of at least 1 line of systemic therapy
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Regorafenib (Stivarga)]] 120 mg PO once per day on days 1 to 21
 '''28-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1002/cncr.31872 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402964/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30561756/ PubMed] [https://clinicaltrials.gov/study/NCT02053376 NCT02053376]
+=Metastatic disease, second-line=
+==FULV {{#subobject:7bhf84|Regimen=1}}==
+FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:15dcq8|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://doi.org/10.1016/s1470-2045(21)00486-1 Yoo et al. 2021 (NIFTY)]
+|2018-09-05 to 2020-02-18
+| style="background-color:#1a9851" |Randomized Phase 2b (C)
+|[[#FULV_.26_nanoliposomal_Irinotecan|FULV & nanoliposomal Irinotecan]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, started on day 1
+*[[Leucovorin (Folinic acid)]] 400 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+'''14-day cycles'''
+</div></div>
+===References===
+#'''NIFTY:''' Yoo C, Kim KP, Jeong JH, Kim I, Kang MJ, Cheon J, Kang BW, Ryu H, Lee JS, Kim KW, Abou-Alfa GK, Ryoo BY. Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study. Lancet Oncol. 2021 Nov;22(11):1560-1572. Epub 2021 Oct 14. [https://doi.org/10.1016/s1470-2045(21)00486-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34656226/ PubMed] [https://clinicaltrials.gov/study/NCT03524508 NCT03524508]
-#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. [https://onlinelibrary.wiley.com/doi/abs/10.1002/cncr.31872 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402964/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30561756 PubMed]
+==FULV & nanoliposomal Irinotecan {{#subobject:7biri4|Regimen=1}}==
+FULV & nanoliposomal Irinotecan: 5-'''<u>FU</u>''', '''<u>L</u>'''euco'''<u>V</u>'''orin, nanoliposomal Irinotecan
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:iricq8|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://doi.org/10.1016/s1470-2045(21)00486-1 Yoo et al. 2021 (NIFTY)]
+|2018-09-05 to 2020-02-18
+| style="background-color:#1a9851" |Randomized Phase 2b (E-esc)
+|[[#FULV_2|FULV]]
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 7.1 vs 1.4 mo<br>(HR 0.56, 95% CI 0.39-0.81)<br><br>Seems to have superior OS (secondary endpoint)<br>Median OS: 8.6 vs 5.5 mo<br>(sHR 0.68, 95% CI 0.48-0.98)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, started on day 1
+*[[Leucovorin (Folinic acid)]] 400 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+*[[Irinotecan liposome (Onivyde)]] 70 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given first'''
+'''14-day cycles'''
+</div></div>
+===References===
+#'''NIFTY:''' Yoo C, Kim KP, Jeong JH, Kim I, Kang MJ, Cheon J, Kang BW, Ryu H, Lee JS, Kim KW, Abou-Alfa GK, Ryoo BY. Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study. Lancet Oncol. 2021 Nov;22(11):1560-1572. Epub 2021 Oct 14. [https://doi.org/10.1016/s1470-2045(21)00486-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34656226/ PubMed] [https://clinicaltrials.gov/study/NCT03524508 NCT03524508]
 [[Category:Gallbladder cancer regimens]]
 [[Category:Disease-specific pages]]
-[[Category:Hepatobiliary cancers]]
+[[Category:Biliary tract cancers]]

Difference between revisions of "Gallbladder cancer"

Latest revision as of 17:47, 23 June 2024

Guidelines

ESMO

NCCN

Adjuvant therapy

Capecitabine monotherapy

Regimen

Preceding treatment

Chemotherapy

References

Capecitabine & Gemcitabine

Regimen

Preceding treatment

Chemotherapy

Subsequent treatment

References

Capecitabine & RT

Regimen

Preceding treatment

Chemotherapy

Radiotherapy

References

GemOx

Regimen

Preceding treatment

Chemotherapy

References

S-1 monotherapy

Regimen

Preceding treatment

Chemotherapy

References

Metastatic or unresectable disease, all lines of therapy

Capecitabine monotherapy

Regimen

Chemotherapy

References

CAPIRI

Regimen

Prior treatment criteria

Chemotherapy

References

Capecitabine & Mitomycin

Regimen

Chemotherapy

Supportive therapy

References

CapeOx

Regimen

Chemotherapy

References

Cisplatin & Gemcitabine (GC)

Regimen

Chemotherapy

Supportive therapy

References

Cisplatin & Gemcitabine (GC) & nab-Paclitaxel

Regimen

Chemotherapy

References

ECF

Regimen

Chemotherapy

References

Erlotinib & Bevacizumab

Regimen

Targeted therapy

References

FELV

Regimen

Chemotherapy

References

FULV & Gemcitabine

Regimen

Chemotherapy

References

Gemcitabine monotherapy

Regimen variant #1

Chemotherapy