Gallbladder cancer
21 regimens on this page
26 variants on this page
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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.
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Guidelines
ESMO
- 2016: Valle et al. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
NCCN
Adjuvant therapy
Capecitabine monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Primrose et al. 2019 (BILCAP) | 2006-2014 | Phase 3 (E-esc) | Observation | Might have superior OS Median OS: 51 vs 36 mo (HR 0.81, 95% CI 0.63-1.04) |
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, Anthony A, Corrie P, Falk S, Finch-Jones M, Wasan H, Ross P, Wall L, Wadsley J, Evans JTR, Stocken D, Praseedom R, Ma YT, Davidson B, Neoptolemos JP, Iveson T, Raftery J, Zhu S, Cunningham D, Garden OJ, Stubbs C, Valle JW, Bridgewater J; BILCAP study group. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019 May;20(5):663-673. Epub 2019 Mar 25. Erratum in: Lancet Oncol. 2019 Apr 2. link to original article PubMed NCT00363584
Capecitabine & Gemcitabine
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GemCap: Gemcitabine & Capecitabine
Regimen
Study | Evidence |
---|---|
Ben-Josef et al. 2015 (SWOG S0809) | Phase 2 |
25 of 79 enrolled patients (32%) had primary gallbladder cancer.
Preceding treatment
Chemotherapy
- Capecitabine (Xeloda) 750 mg/m2/day PO twice per day on days 1 to 14
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
Subsequent treatment
- Capecitabine & RT
References
- SWOG S0809: Ben-Josef E, Guthrie KA, El-Khoueiry AB, Corless CL, Zalupski MM, Lowy AM, Thomas CR Jr, Alberts SR, Dawson LA, Micetich KC, Thomas MB, Siegel AB, Blanke CD. SWOG S0809: A phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol. 2015 Aug 20;33(24):2617-22. Epub 2015 May 11. link to original article link to PMC article contains verified protocol PubMed
GemOx
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GemOx: Gemcitabine & Oxaliplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Edeline et al. 2019 (PRODIGE 12-ACCORD 18-UNICANCER GI) | 2009-2014 | Phase 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
Metastatic or unresectable disease, all lines of therapy
Capecitabine monotherapy
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Regimen
Study | Evidence |
---|---|
Patt et al. 2004 | Retrospective |
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
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CAPIRI: CAPecitabine & IRInotecan
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ramaswami et al. 2020 (GB-SELECT) | 2018-2020 | Randomized Phase 2 (E-esc) | Irinotecan | No significant difference in OS |
All patients had progressed 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 verified protocol link to PMC article PubMed CTRI/2017/10/010112
Capecitabine & Mitomycin
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kornek et al. 2004 | 2000-2001 | Randomized Phase 2 (E-switch-ic) | Gemcitabine & Mitomycin | Might have superior ORR |
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 medications
- Dexamethasone (Decadron) and 5-HT3 antagonists on the day of IV chemotherapy
28-day cycles
References
- Kornek GV, Schuell B, Laengle F, Gruenberger T, Penz M, Karall K, Depisch D, Lang F, Scheithauer W. Mitomycin C in combination with capecitabine or biweekly high-dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial. Ann Oncol. 2004 Mar;15(3):478-83. link to original article contains verified protocol PubMed
CapeOx
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CapeOx: Capecitabine & Oxaliplatin
XELOX: XELoda (Capecitabine) & OXaliplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kim et al. 2019 (SMC 2011-05-070) | 2011-2016 | Phase 3 (E-switch-ic) | GEMOX | Non-inferior PFS |
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 protocol PubMed
Cisplatin & Gemcitabine (GC)
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GC: Gemcitabine & Cisplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Valle et al. 2010 (ABC-02) | 2002-2008 | Phase 3 (E-esc) | Gemcitabine | Superior OS |
Sharma et al. 2019 | 2011-2015 | Phase 3 (C) | 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 |
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 medications
- Cisplatin is mixed in a solution of 1 liter of normal saline with 20 mmol potassium chloride, 8 mmol magnesium sulfate
- After cisplatin, 500 mL normal saline given over 30 minutes
21-day cycle for 4 to 8 cycles depending on response
References
- ABC-02: Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. link to original article contains verified protocol PubMed
- FUGA-BT: Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, Ozaka M, Okano N, Sugimori K, Fukutomi A, Hara H, Mizuno N, Yanagimoto H, Wada K, Tobimatsu K, Yane K, Nakamori S, Yamaguchi H, Asagi A, Yukisawa S, Kojima Y, Kawabe K, Kawamoto Y, Sugimoto R, Iwai T, Nakamura K, Miyakawa H, Yamashita T, Hosokawa A, Ioka T, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J. Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. Ann Oncol. 2019 Dec 1;30(12):1950-1958. link to original article PubMed
- 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 verified protocol PubMed CTRI/2010/091/001406
Cisplatin & Gemcitabine (GC) & nab-Paclitaxel
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Regimen
Study | Evidence |
---|---|
Shroff et al. 2019 (MDACC 2014-0524) | Phase 2 |
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 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. link to original article link to PMC article PubMed NCT02392637
ECF
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ECF: Epirubicin, Cisplatin, Fluorouracil
Regimen
Study | Years 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 |
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 verified protocol link to PMC article PubMed
Erlotinib & Bevacizumab
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Regimen
Study | Evidence |
---|---|
Lubner et al. 2010 (MC044G) | Phase 2 |
10 of 54 patients (19%) included in endpoint analysis had primary gallbladder cancer.
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day
- Bevacizumab (Avastin) 5 mg/kg IV once per day on days 1 & 15
28-day cycles
References
- 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 verified protocol link to PMC article PubMed NCT00356889
FELV
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FELV: Fluorouracil , Etoposide, LeucoVorin (Folinic acid)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rao et al. 2005 | 1997-2003 | Phase 3 (C) | ECF | Did not meet primary endpoint of OS |
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
- Folinic acid (Leucovorin) 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 verified protocol link to PMC article PubMed
FULV & Gemcitabine
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FULV & Gemcitabine: 5-FU, LeucoVorin (Folinic acid), Gemcitabine
Regimen
Study | Evidence |
---|---|
Gebbia et al. 2001 | Phase 2 |
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)
- Folinic acid (Leucovorin) 100 mg/m2 IV over 2 hours once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Gebbia V, Giuliani F, Maiello E, Colucci G, Verderame F, Borsellino N, Mauceri G, Caruso M, Tirrito ML, Valdesi M. Treatment of inoperable and/or metastatic biliary tree carcinomas with single-agent gemcitabine or in combination with levofolinic acid and infusional fluorouracil: results of a multicenter phase II study. J Clin Oncol. 2001 Oct 15;19(20):4089-91. link to original article contains verified protocol PubMed
Gemcitabine monotherapy
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Regimen variant #1
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Valle et al. 2010 (ABC-02) | 2002-2008 | Phase 3 (E-de-esc) | GC | Inferior OS |
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 |
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 verified protocol PubMed
- ABC-02: Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. link to original article contains verified protocol PubMed
Gemcitabine, Cisplatin, S-1
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GCS: Gemcitabine, Cisplatin, S-1
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sakai et al. 2018 (KHBO1401-MITSUBA) | 2014-NR | Phase 3 (E-esc) | GC | Seems to have superior OS |
Although patients with primary gallbladder cancer met eligibility criteria, the relative number of patients enrolled was not reported in the presented abstract.
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once on day 1
- Tegafur, gimeracil, oteracil (S-1) 80 mg/m2 PO once per day on days 1 to 7
14-day cycles
References
- Abstract: Sakai D, Kanai M , Kobayashi S, Eguchi H, Baba H, Seo S, Taketomi A, Takayama T, Yamaue H, Ishioka C, Sho M, Takeyama Y, Fujimoto J, Toyoda M, Shimizu J, Goto T, Yoshimura K, Hatano E, Nagano H, Ioka T. Randomized phase III study of gemcitabine, cisplatin plus S-1 (GCS) versus gemcitabine, cisplatin (GC) for advanced biliary tract cancer (KHBO1401-MITSUBA). Annals of Oncology 29 (Supplement 8): viii205–viii270, 2018 link to abstract
Gemcitabine & Mitomycin
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kornek et al. 2004 | 2000-2001 | Randomized Phase 2 (E-switch-ic) | Capecitabine & Mitomycin | Might have inferior ORR |
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 medications
- Dexamethasone (Decadron) and 5-HT3 antagonists on the day of IV chemotherapy
28-day cycles
References
- Kornek GV, Schuell B, Laengle F, Gruenberger T, Penz M, Karall K, Depisch D, Lang F, Scheithauer W. Mitomycin C in combination with capecitabine or biweekly high-dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial. Ann Oncol. 2004 Mar;15(3):478-83. link to original article contains verified protocol PubMed
Gemcitabine & S-1
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GS: Gemcitabine & S-1
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Morizane et al. 2019 (FUGA-BT) | 2013-2016 | Phase 3 (E-switch-ic) | Gemcitabine & Cisplatin | Seems to have non-inferior OS |
137 of 354 enrolled patients (39%) had primary gallbladder cancer.
Chemotherapy
References
- FUGA-BT: Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, Ozaka M, Okano N, Sugimori K, Fukutomi A, Hara H, Mizuno N, Yanagimoto H, Wada K, Tobimatsu K, Yane K, Nakamori S, Yamaguchi H, Asagi A, Yukisawa S, Kojima Y, Kawabe K, Kawamoto Y, Sugimoto R, Iwai T, Nakamura K, Miyakawa H, Yamashita T, Hosokawa A, Ioka T, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J. Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. Ann Oncol. 2019 Dec 1;30(12):1950-1958. link to original article PubMed
GemOx
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GemOx: Gemcitabine & Oxaliplatin
mGEMOX: modified GEMcitabine & OXaliplatin
Regimen variant #1, 900/80 ("mGEMOX")
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sharma et al. 2010 | 2006-2008 | Randomized (E-esc) | 1. Best supportive care | Seems to have superior OS |
2. FUFA | Not reported | |||
Sharma et al. 2019 | 2011-2015 | Phase 3 (C) | CisGem | Inconclusive whether non-inferior OS |
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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2011 (SMC 2008-12-024) | 2009-2010 | 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) |
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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kim et al. 2019 (SMC 2011-05-070) | 2011-2016 | Phase 3 (C) | XELOX | Non-inferior PFS |
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 | Evidence | Efficacy |
---|---|---|
Halim et al. 2011 | Phase 2 | ORR: 27.5% |
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
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
- 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 protocol PubMed
- SMC 2008-12-024: Lee J, Park SH, Chang HM, Kim JS, Choi HJ, Lee MA, Jang JS, Jeung HC, Kang JH, Lee HW, Shin DB, Kang HJ, Sun JM, Park JO, Park YS, Kang WK, Lim HY. Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2012 Feb;13(2):181-8. Epub 2011 Dec 20. link to original article contains protocol PubMed
- SMC 2011-05-070: Kim ST, Kang JH, Lee J, Lee HW, Oh SY, Jang JS, Lee MA, Sohn BS, Yoon SY, Choi HJ, Hong JH, Kim MJ, Kim S, Park YS, Park JO, Lim HY. Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial. Ann Oncol. 2019 May 1;30(5):788-795. link to original article contains protocol PubMed
- Halim A, Ebrahim MA, Saleh Y. A phase II study of outpatient biweekly gemcitabine-oxaliplatin in advanced biliary tract carcinomas. Jpn J Clin Oncol. 2011 Feb;41(2):217-24. link to original article contains verified protocol PubMed
- Harder J, Riecken B, Kummer O, Lohrmann C, Otto F, Usadel H, Geissler M, Opitz O, Henss H. Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer. Br J Cancer. 2006 Oct 9;95(7):848-52. link to original article link to PMC article contains verified protocol 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. link to original article contains verified protocol PubMed CTRI/2010/091/001406
GEMOX-B
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GEMOX-B: GEMcitabine, OXaliplatin, Bevacizumab
Regimen
Study | Evidence |
---|---|
Zhu et al. 2009 (MGH 05-349) | Phase 2 |
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 verified protocol PubMed
Irinotecan monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ramaswami et al. 2020 (GB-SELECT) | 2018-2020 | Randomized Phase 2 (C) | Capecitabine & Irinotecan | No significant difference in OS |
All patients had progressed 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 verified protocol link to PMC article PubMed CTRI/2017/10/010112
Regorafenib monotherapy
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Regimen
Study | Evidence |
---|---|
Sun et al. 2019 (UPMC 13-100) | Phase 2 |
Only studied in patients with advanced biliary cancer who failed at least 1 line of systemic therapy.
5 of 43 enrolled patients (12%) had primary gallbladder cancer.
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 PubMed NCT02053376