Pancreatic cancer

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Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it! 
Note: this page contains regimens for the most common histologic type of pancreatic cancer - pancreatic adenocarcinoma. For the most part, regimens here were not tested in biomarker-specific populations. The following links will take you to biomarker- and histology-specific subpages:
*Regimens for BRCA-mutated pancreatic cancer are here.
*Regimens for NRG1-positive pancreatic cancer are here.
*Regimens for Pancreatic neuroendocrine tumor (NET) are here.
Last updated on 2024-12-02:51 regimens on this page
87 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ASCO==
*2020: Sohal et al. Metastatic Pancreatic Cancer: ASCO Guideline Update EuroPMC
**2018: Sohal et al. Metastatic pancreatic cancer: ASCO Clinical Practice Guideline update link to PMC article EuroPMC
**2016: Sohal et al. Metastatic pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline EuroPMC
*2019: Khorana et al. Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update EuroPMC
**2017: Khorana et al. Potentially curable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline update EuroPMC
*2018: Stoffel et al. Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion EuroPMC
*2016: Balaban et al. Locally advanced, unresectable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline EuroPMC
==ESMO==
*2023: Conroy et al. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up EuroPMC
**2015: Ducreux et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2010: Cascinu et al. Pancreatic cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2009: Cascinu & Jelic. Pancreatic cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2008: Herrmann & Jelic. Pancreatic cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2007: Herrmann. Pancreatic cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2005: Herrmann et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of pancreatic cancer EuroPMC
*2019: Stjepanovic et al. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
==French Intergroup==
*2018: Neuzillet et al. Pancreatic cancer: French clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC) EuroPMC
==NCCN==
*NCCN Guidelines - Pancreatic Adenocarcinoma
**2021: Tempero et al. Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. EuroPMC
**2019: Tempero et al. Pancreatic Adenocarcinoma, Version 1.2019. EuroPMC
**2017: Tempero et al. Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. EuroPMC
**2014: Tempero et al. Pancreatic Adenocarcinoma, Version 2.2014 EuroPMC
**2012: Tempero et al. Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. link to PMC article EuroPMC
**2010: Tempero et al. Pancreatic adenocarcinoma. link to PMC article EuroPMC
**2007: Tempero et al. Pancreatic adenocarcinoma. Clinical Practice Guidelines in Oncology. EuroPMC
**2005: Tempero et al. Pancreatic adenocarcinoma: Clinical Practice Guidelines in Oncology. EuroPMC
=Adjuvant therapy=
==Capecitabine & Gemcitabine==
GemCap: Gemcitabine & Capecitabine
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Neoptolemos et al. 2017 (ESPAC-4)	2008-2014 	Phase 3 (E-RT-esc)	Gemcitabine	Seems to have longer OS (primary endpoint)Median OS: 28 vs 25.5 mo(HR 0.82, 95% CI 0.68-0.98)
Treatment starts within 12 weeks of surgery.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Capecitabine (Xeloda) 1660 mg/m2/day PO on days 1 to 21 (frequency of dosing not specified)
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycle for 6 cycles
===References===
#ESPAC-4: Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW; European Study Group for Pancreatic Cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017 Mar 11;389(10073):1011-1024. Epub 2017 Jan 25. link to original article dosing details in abstract have been reviewed by our editors EuroPMC ISRCTN96397434
==FULV==
FULV: 5-FU & LeucoVorin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Neoptolemos et al. 2001 (ESPAC-1) 	1994-2000 	Phase 3 (E-esc)	1. 5-FU & RT2. 5-FU & RT/FULV 	Seems to have longer OS1 (primary endpoint)
Neoptolemos et al. 2001 (ESPAC-1) 	1994-2000 	Phase 3 (E-esc)	3. Observation 	Longer OS1 (primary endpoint)Median OS: 20.1 vs 15.5 mo(HR 0.71, 95% CI 0.55-0.92)
Neoptolemos et al. 2010 (ESPAC-3 version 2)	2003-2007 	Phase 3 (C) 	Gemcitabine 	Did not meet primary endpoint of OSMedian OS: 23 vs 23.6 mo(HR 1.06, 95% CI 0.93-1.23)
Schmidt et al. 2012 (CapRI) 	2004-2007 	Phase 3 (C) 	5-FU, Cisplatin, IFN alfa-2b, RT	Did not meet primary endpoint of OSMedian OS: 28.5 vs 26.5 mo(HR 0.96, 95% CI 0.65-1.52)
1Reported efficacy for ESPAC-1 is based on the 2004 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) 425 mg/m2 IV bolus once per day on days 1 to 5, given second
*Leucovorin (Folinic acid) 20 mg/m2 IV bolus once per day on days 1 to 5, given first
28-day cycle for 6 cycles
===References===
#ESPAC-1: Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C, Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A, Spooner D, Kerr DJ, Friess H, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001 Nov 10;358(9293):1576-85. link to original article EuroPMC
##Update: Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW; European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004 Mar 18;350(12):1200-10. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#ESPAC-3 version 2: Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Oláh A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010 Sep 8;304(10):1073-81. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00058201
#CapRI: Schmidt J, Abel U, Debus J, Harig S, Hoffmann K, Herrmann T, Bartsch D, Klein J, Mansmann U, Jäger D, Capussotti L, Kunz R, Büchler MW. Open-label, multicenter, randomized phase III trial of adjuvant chemoradiation plus interferon alfa-2b versus fluorouracil and folinic acid for patients with resected pancreatic adenocarcinoma. J Clin Oncol. 2012 Nov 20;30(33):4077-83. Epub 2012 Sep 24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN62866759
==Fluorouracil/Fluorouracil & RT==
Fluorouracil/Fluorouracil & RT: Fluorouracil alternating with Fluorouracil & Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Regine et al. 2008 (RTOG 9704)	1998-2002 	Phase 3 (C)	Gemcitabine/5-FU & RT	Might have shorter OS2Median OS: 17.1 vs 20.5 mo(HR 1.19, 95% CI 0.95-1.49)
2Reported efficacy is based on the 2011 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Fluorouracil (5-FU) as follows: 
**Cycle 1: 250 mg/m2/day IV continuous infusion over 21 days, started on day 1 (total dose: 5000 mg/m2)
**Cycle 2 (chemoradiation): 250 mg/m2/day IV continuous infusion throughout radiation therapy
**Cycles 3 & 4: 250 mg/m2/day IV continuous infusion over 28 days, started on day 1 (total dose per cycle: 7000 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy during cycle 2: 180 cGy fractions x 28 fractions, for a total dose of 5040 cGy. The last 540 cGy of the 5040 cGy is limited to the tumor bed.
4- to 5-week course, then 9- to 11-week course, then 6-week cycle for 2 cycles
===References===
#RTOG 9704: Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5;299(9):1019-26. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003216
##Update: Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the US Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26. Epub 2011 Mar 10. link to original article link to PMC article EuroPMC
==mFOLFIRINOX==
mFOLFIRINOX: modified FOLinic acid (Leucovorin), Fluorouracil, IRINotecan, OXaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Conroy et al. 2018 (NCIC-CTG PA.6)	2012-2016 	Phase 3 (E-esc)	Gemcitabine	Longer DFS1 (primary endpoint)Median DFS: 21.4 vs 12.8 mo(HR 0.66, 95% CI 0.54-0.82)Longer OS1 (secondary endpoint)Median OS: 53.5 vs 35.5 mo(HR 0.68, 95% CI 0.54-0.85)	More toxic
1Reported efficacy is based on the 2022 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given second
*Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1, given fourth
*Irinotecan (Camptosar) 150 mg/m2 IV over 90 minutes once on day 1, given third
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first
14-day cycle for 12 cycles
===References===
#NCIC-CTG PA.6: Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Choné L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Breysacher G, Di Fiore F, Cripps C, Kavan P, Texereau P, Bouhier-Leporrier K, Khemissa-Akouz F, Legoux JL, Juzyna B, Gourgou S, O'Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet JB; NCIC-CTG; Unicancer-GI–PRODIGE Group. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018 Dec 20;379(25):2395-2406. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01526135
##Update: Conroy T, Castan F, Lopez A, Turpin A, Ben Abdelghani M, Wei AC, Mitry E, Biagi JJ, Evesque L, Artru P, Lecomte T, Assenat E, Bauguion L, Ychou M, Bouché O, Monard L, Lambert A, Hammel P; Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial. JAMA Oncol. 2022 Nov 1;8(11):1571-1578. Epub 2022 Sep 1. link to original article link to PMC article EuroPMC
#Alliance A021806: NCT04340141
==Gemcitabine monotherapy==
===Regimen variant #1, 2 out of 3 weeks===
Study 	Dates of enrollment	Evidence
Landry et al. 2010 (ECOG E1200)	2003-2005 	Phase 2
====Preceding treatment====
*Induction Gemcitabine & RT, then surgery
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 100 minutes once per day on days 1 & 8
21-day cycle for 5 cycles
===Regimen variant #2, 3 out of 4 weeks===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Oettle et al. 2007 (CONKO-001) 	1998-2004 	Phase 3 (E-esc) 	Observation 	Longer OS1 (secondary endpoint)OS60: 20.7% vs 10.4%(HR 0.76, 95% CI 0.61-0.95)
Ueno et al. 2009 (JSAP-02) 	2002-2005 	Phase 3 (E-esc) 	Observation 	Did not meet primary endpoint of OSMedian OS: 22.3 vs 18.4 mo(HR 0.77, 95% CI 0.51-1.14)
Neoptolemos et al. 2010 (ESPAC-3 version 2)	2003-2007 	Phase 3 (E-switch-ic)	FULV 	Did not meet primary endpoint of OSMedian OS: 23.6 vs 23 mo(HR 0.94, 95% CI 0.81-1.08)
Uesaka et al. 2016 (JASPAC 01) 	2007-2010 	Phase 3 (C) 	S-1 	Shorter OSOS60: 24.4% vs 44.1%(HR 1.75, 95% CI 1.39-2.27)
Sinn et al. 2017 (CONKO-005) 	2008-2013 	Phase 3 (C) 	Erlotinib & Gemcitabine 	Did not meet primary endpoint of DFSMedian DFS: 11.4 vs 11.4 mo(HR 1.06, 95% CI 0.87-1.32)
Neoptolemos et al. 2017 (ESPAC-4) 	2008-2014 	Phase 3 (C) 	Capecitabine & Gemcitabine 	Seems to have shorter OSMedian OS: 25.5 vs 28 mo(HR 1.22, 95% CI 1.02-1.47)
Conroy et al. 2018 (NCIC-CTG PA.6) 	2012-2016 	Phase 3 (C) 	mFOLFIRINOX 	Shorter DFS2 (primary endpoint)Median DFS: 12.8 vs 21.4 mo(HR 1.52, 95% CI 1.22-1.85)Shorter OS2 (secondary endpoint)Median OS: 35.5 vs 53.5 mo(HR 1.47, 95% CI 1.18-1.85)
Tempero et al. 2023 (APACT) 	2014-04 to 2016-04 	Phase 3 (C) 	Gemcitabine & nab-Paclitaxel	Did not meet primary endpoint of DFSMedian DFS: 18.8 vs 19.4 mo(HR 1.14, 95% CI 0.94-1.37)
1Reported efficacy for CONKO-001 is based on the 2013 update.
2Reported efficacy for NCIC-CTG PA.6 is based on the 2013 update.
Note: Treatment starts day 10 to 42 after surgery or after wound is healed.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for up to 6 cycles
===References===
#CONKO-001: Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007 Jan 17;297(3):267-77. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN34802808
##Update: Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zülke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013 Oct 9;310(14):1473-81. link to original article EuroPMC
#JSAP-02: Ueno H, Kosuge T, Matsuyama Y, Yamamoto J, Nakao A, Egawa S, Doi R, Monden M, Hatori T, Tanaka M, Shimada M, Kanemitsu K; Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer. 2009 Sep 15;101(6):908-15. Epub 2009 Aug 18. link to original article link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#ECOG E1200: Landry J, Catalano PJ, Staley C, Harris W, Hoffman J, Talamonti M, Xu N, Cooper H, Benson AB 3rd. Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. J Surg Oncol. 2010 Jun 1;101(7):587-92. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
#ESPAC-3 version 2: Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Oláh A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010 Sep 8;304(10):1073-81. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00058201
#JASPAC 01: Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T, Ohashi Y; JASPAC 01 Study Group. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016 Jul 16;388(10041):248-57. Epub 2016 Jun 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000000655
##HRQoL analysis: Hagiwara Y, Ohashi Y, Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T; JASPAC 01 Study Group. Health-related quality of life of adjuvant chemotherapy with S-1 versus gemcitabine for resected pancreatic cancer: Results from a randomised phase III trial (JASPAC 01). Eur J Cancer. 2018 Apr;93:79-88. link to original article link to EuroPMC
#ESPAC-4: Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW; European Study Group for Pancreatic Cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017 Mar 11;389(10073):1011-1024. Epub 2017 Jan 25. link to original article dosing details in abstract have been reviewed by our editors EuroPMC ISRCTN96397434
#CONKO-005: Sinn M, Bahra M, Liersch T, Gellert K, Messmann H, Bechstein W, Waldschmidt D, Jacobasch L, Wilhelm M, Rau BM, Grützmann R, Weinmann A, Maschmeyer G, Pelzer U, Stieler JM, Striefler JK, Ghadimi M, Bischoff S, Dörken B, Oettle H, Riess H. CONKO-005: adjuvant chemotherapy with gemcitabine plus erlotinib versus gemcitabine alone in patients after R0 resection of pancreatic cancer: a multicenter randomized phase III trial. J Clin Oncol. 2017 Oct 10;35(29):3330-3337. Epub 2017 Aug 17. link to original article dosing details in abstract have been reviewed by our editors EuroPMC DRKS00000247
#NCIC-CTG PA.6: Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Choné L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Breysacher G, Di Fiore F, Cripps C, Kavan P, Texereau P, Bouhier-Leporrier K, Khemissa-Akouz F, Legoux JL, Juzyna B, Gourgou S, O'Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet JB; NCIC-CTG; Unicancer-GI–PRODIGE Group. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018 Dec 20;379(25):2395-2406. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01526135
##Update: Conroy T, Castan F, Lopez A, Turpin A, Ben Abdelghani M, Wei AC, Mitry E, Biagi JJ, Evesque L, Artru P, Lecomte T, Assenat E, Bauguion L, Ychou M, Bouché O, Monard L, Lambert A, Hammel P; Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial. JAMA Oncol. 2022 Nov 1;8(11):1571-1578. Epub 2022 Sep 1. link to original article link to PMC article EuroPMC
#APACT: Tempero MA, Pelzer U, O'Reilly EM, Winter J, Oh DY, Li CP, Tortora G, Chang HM, Lopez CD, Bekaii-Saab T, Ko AH, Santoro A, Park JO, Noel MS, Frassineti GL, Shan YS, Dean A, Riess H, Van Cutsem E, Berlin J, Philip P, Moore M, Goldstein D, Tabernero J, Li M, Ferrara S, Le Bruchec Y, Zhang G, Lu B, Biankin AV, Reni M. Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2023 Apr 10;41(11):2007-2019. Epub 2022 Dec 15. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT01964430
#NLG0405: NCT01072981
==Gemcitabine/Fluorouracil & RT==
Gemcitabine/Fluorouracil & RT: Gemcitabine alternating with Fluorouracil & Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Regine et al. 2008 (RTOG 9704)	1998-2002 	Phase 3 (E-switch-ic)	5-FU & RT 	Might have longer OS1Median OS: 20.5 vs 17.1 mo(HR 0.84, 95% CI 0.67-1.05)
1Reported efficacy is based on the 2011 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Gemcitabine (Gemzar) as follows:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
**Cycles 3 to 5: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
*Fluorouracil (5-FU) as follows:
**Cycle 2 (chemoradiation): 250 mg/m2/day IV continuous infusion throughout radiation therapy
====Radiotherapy====
*Concurrent radiation therapy during cycle 2: 180 cGy fractions x 28 fractions, for a total dose of 5040 cGy. The last 540 cGy of the 5040 cGy is limited to the tumor bed.
4- to 5-week course, then 9- to 11-week course, then 28-day cycle for 3 cycles
===References===
#RTOG 9704: Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5;299(9):1019-26. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003216
##Update: Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the US Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26. Epub 2011 Mar 10. link to original article link to PMC article EuroPMC
==S-1 monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Uesaka et al. 2016 (JASPAC 01)	2007-2010 	Phase 3 (E-switch-ic)	Gemcitabine	Longer OS (primary endpoint)OS60: 44.1% vs 24.4%(HR 0.57, 95% CI 0.44-0.72)
Treatment starts 10 to 42 days after surgery or after wound is healed.
====Preceding treatment====
*Surgery
====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 up to 1.50 m2: 50 mg PO twice per day on days 1 to 28
**1.50 m2 or more: 60 mg PO twice per day on days 1 to 28
42-day cycle for up to 4 cycles
===References===
#JASPAC 01: Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T, Ohashi Y; JASPAC 01 Study Group. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016 Jul 16;388(10041):248-57. Epub 2016 Jun 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000000655
##HRQoL analysis: Hagiwara Y, Ohashi Y, Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T; JASPAC 01 Study Group. Health-related quality of life of adjuvant chemotherapy with S-1 versus gemcitabine for resected pancreatic cancer: Results from a randomised phase III trial (JASPAC 01). Eur J Cancer. 2018 Apr;93:79-88. link to original article link to EuroPMC
=Induction therapy for locally advanced disease, potentially resectable=
==Docetaxel, Gemcitabine, RT==
DG & RT: Docetaxel, Gemcitabine, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Pipas et al. 2005	2002-2004 	Phase 2
====Chemotherapy====
*Docetaxel (Taxotere) as follows:
**Cycles 1 to 3: 65 mg/m2 IV over 60 minutes once on day 1
*Gemcitabine (Gemzar) as follows:
**Cycles 1 to 3: 4000 mg/m2 IV over 30 minutes once on day 1
**Cycles 4 to 6 (chemoradiation): 50 mg/m2 IV over 30 minutes once per day on either days 1, 4, 8, 11 or days 2, 5, 9, 12, completed 30 minutes to 2 hours prior to RT
====Supportive therapy====
*GI prophylaxis with a proton pump inhibitor
====Radiotherapy====
*Concurrent radiation therapy as follows:
**Cycles 4 to 6: 180 cGy fractions x 25 fractions, for a total dose of 4500 cGy to primary target volume. Then 540 cGy boost to secondary target volume of 1- to 1.5-cm margin on all sides, including proven nodal involvement. Total 5040 cGy in 28 fractions.
14-day cycle for 6 cycles
===References===
#Pipas JM, Barth RJ Jr, Zaki B, Tsapakos MJ, Suriawinata AA, Bettmann MA, Cates JM, Ripple GH, Sutton JE, Gordon SR, McDonnell CE, Perez RP, Redfield N, Meyer LP, Marshall JF, Cole BF, Colacchio TA. Docetaxel/Gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma. Ann Surg Oncol. 2005 Dec;12(12):995-1004. Epub 2005 Nov 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Gemcitabine & RT==
Gemcitabine & RT: Gemcitabine & Radiation Therapy
===Regimen variant #1, 400 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Jang et al. 2018 (BorderlinePancreas)	2012-2014 	Phase 2/3 (E-esc)	No neoadjuvant therapy	Seems to have higher OS24 (primary endpoint)
====Chemotherapy====
*Gemcitabine (Gemzar) 400 mg/m2 IV over 50 minutes once per day on days 1, 8, 15, 22, 29, 36
====Radiotherapy====
*Concurrent radiation therapy, 4500 cGy in 25 fractions, then 900 cGy in 5 fractions
6-week course
====Subsequent treatment====
*Surgery
===Regimen variant #2, 500 mg/m2===
Study 	Dates of enrollment	Evidence
Landry et al. 2010 (ECOG E1200)	2003-2005 	Phase 2
====Chemotherapy====
*Gemcitabine (Gemzar) 500 mg/m2 IV over 50 minutes once per day on days 1, 8, 15, 22, 29, 36
====Radiotherapy====
*Concurrent radiation therapy, 180 cGy x 22 with 3 cm margin to GTV then 180 cGy x 6 with 2 cm margin to GTV, total 5040 cGy over 6 weeks
6-week course
====Subsequent treatment====
*Restaging after radiation complete. 4 to 6 week break, then surgery, then 4 to 8 week break, then adjuvant gemcitabine
===Regimen variant #3, 600 mg/m2===
Study 	Dates of enrollment	Evidence
Hosein et al. 2012	2008-05 to 2011-05 	Retrospective
====Preceding treatment====
*mFOLFIRINOX induction
====Chemotherapy====
*Gemcitabine (Gemzar) 600 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
====Radiotherapy====
*External beam radiotherapy at 5040 cGy in 28 fractions.
6-week course
===Regimen variant #4, 1000 mg/m2===
Study 	Dates of enrollment	Evidence
Takahashi et al. 2013	Not reported 	Phase 2
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15, 29, 36, 43, 57, 65, 72
====Radiotherapy====
*Concurrent radiation therapy, 200 cGy per fraction x 25 fractions, total dose of 5000 cGy
12-week course
====Subsequent treatment====
*Restaging is performed 8 weeks after radiation complete (2 weeks after chemotherapy complete). Resection immediately thereafter, if feasible
===Regimen variant #5, 1000 mg/m2, short course RT===
Study 	Dates of enrollment	Evidence
Blazer et al. 2014	2011-01 to 2013-08 	Retrospective
====Preceding treatment====
*mFOLFIRINOX induction
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
====Radiotherapy====
*External beam radiotherapy 240 cGy per day on days 1 to 5, 8 to 12, 15 to 19 (3600 cGy in 15 daily fractions)
3-week course
===Regimen variant #6, 1000 mg/m2, short course RT variant 2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Versteijne et al. 2020 (PREOPANC)	2013-2017 	Phase 3 (E-esc)	Gemcitabine	Seems to have longer OS (primary endpoint)1Median OS: 15.7 vs 14.3 mo(HR 0.73, 95% CI 0.56-0.96)
1Reported efficacy is based on the 2022 update.
====Chemotherapy====
*Gemcitabine (Gemzar) as follows:
**Cycle 1: 1000 mg/m2 IV once per day on days 1 & 8
**Cycle 2 (chemoradiation): 1000 mg/m2 IV once per day on days 1, 8, 15
====Radiotherapy====
*Concurrent radiation therapy during cycle 2: 240 cGy in 3 weeks to the pancreatic tumor and suspicious lymph nodes
21-day cycle, then 8-week course
====Subsequent treatment====
*Surgical resection, then adjuvant Gemcitabine
===References===
#ECOG E1200: Landry J, Catalano PJ, Staley C, Harris W, Hoffman J, Talamonti M, Xu N, Cooper H, Benson AB 3rd. Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. J Surg Oncol. 2010 Jun 1;101(7):587-92. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
#Retrospective: Hosein PJ, Macintyre J, Kawamura C, Maldonado JC, Ernani V, Loaiza-Bonilla A, Narayanan G, Ribeiro A, Portelance L, Merchan JR, Levi JU, Rocha-Lima CM. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012 May 29;12:199. link to original article link to PMC article EuroPMC
#Takahashi H, Ohigashi H, Gotoh K, Marubashi S, Yamada T, Murata M, Ioka T, Uehara H, Yano M, Ishikawa O. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg. 2013 Dec;258(6):1040-50. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000001804
#Retrospective: Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, Wuthrick E, Williams TM, Reardon J, Christopher Ellison E, Bloomston M, Bekaii-Saab T. Neoadjuvant Modified (m) FOLFIRINOX for Locally Advanced Unresectable (LAPC) and Borderline Resectable (BRPC) Adenocarcinoma of the Pancreas. Ann Surg Oncol. 2015 Apr;22(4):1153-9. Epub 2014 Oct 31. link to original article link to PMC article EuroPMC
#BorderlinePancreas: Jang JY, Han Y, Lee H, Kim SW, Kwon W, Lee KH, Oh DY, Chie EK, Lee JM, Heo JS, Park JO, Lim DH, Kim SH, Park SJ, Lee WJ, Koh YH, Park JS, Yoon DS, Lee IJ, Choi SH. Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial. Ann Surg. 2018 Aug;268(2):215-222. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01458717
#PREOPANC: Versteijne E, Suker M, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, Buijsen J, Busch OR, Creemers GM, van Dam RM, Eskens FALM, Festen S, de Groot JWB, Groot Koerkamp B, de Hingh IH, Homs MYV, van Hooft JE, Kerver ED, Luelmo SAC, Neelis KJ, Nuyttens J, Paardekooper GMRM, Patijn GA, van der Sangen MJC, de Vos-Geelen J, Wilmink JW, Zwinderman AH, Punt CJ, van Eijck CH, van Tienhoven G; Dutch Pancreatic Cancer Group. Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial. J Clin Oncol. 2020 Jun 1;38(16):1763-1773. Epub 2020 Feb 27. link to original article link to PMC article EuroPMC EudraCT 2012-003181-40
##Update: Versteijne E, van Dam JL, Suker M, Janssen QP, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, Buijsen J, Busch OR, Creemers GM, van Dam RM, Eskens FALM, Festen S, de Groot JWB, Groot Koerkamp B, de Hingh IH, Homs MYV, van Hooft JE, Kerver ED, Luelmo SAC, Neelis KJ, Nuyttens J, Paardekooper GMRM, Patijn GA, van der Sangen MJC, de Vos-Geelen J, Wilmink JW, Zwinderman AH, Punt CJ, van Tienhoven G, van Eijck CHJ; Dutch Pancreatic Cancer Group. Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin Oncol. 2022 Apr 10;40(11):1220-1230. Epub 2022 Jan 27. link to original article EuroPMC
#PREOPANC-2: EudraCT 2017-002036-17
==Gemcitabine, Cetuximab, RT==
Gemcitabine, Cetuximab, RT: Gemcitabine, Cetuximab, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Pipas et al. 2012	2005-2008 	Phase 2
Note: Gemcitabine could be given on days 1 & 4 or days 2 & 5 of each week.
====Chemotherapy====
*Gemcitabine (Gemzar) 50 mg/m2 IV over 30 minutes once per day on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, 39, completed 30 minutes to 2 hours prior to RT
====Targeted therapy====
*Cetuximab (Erbitux) as follows:
**6 to 8 days prior radiation: 400 mg/m2 IV over 2 hours once
**During radiation: 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
====Radiotherapy====
*Concurrent radiation therapy, delivered using IMRT. Gross tumor volume (GTV) was all known disease including imaging proven nodal disease. The primary planning target volume (PTV1) included the GTV with 2- to 3-cm margins in all directions as well as potential nodal involvement. Secondary planning target volume (PTV2) included the GTV with 1- to 1.5-cm margins on all sides including proven nodal involvement. Tertiary planning treatment volume (PTV3) included the area of the GTV adjacent to the vascular structures specifically the mesenteric and portal vessels with a 0.5-cm margin. The prescription dose delivered to PTV3 was 5400 cGy in 28 fractions. Synchronously, PTV1 and PTV2 received 45 and 5040 cGy, respectively.
====Supportive therapy====
*GI prophylaxis with a proton pump inhibitor during chemoradiotherapy
6-week course
====Subsequent treatment====
*One month following therapy, patients were restaged with CT scan of chest/abdomen/pelvis. Patients deemed to be candidates for surgical resection were offered laparotomy ∼6 to 10 weeks after completion of neoadjuvant therapy.
===References===
#Pipas JM, Zaki BI, McGowan MM, Tsapakos MJ, Ripple GH, Suriawinata AA, Tsongalis GJ, Colacchio TA, Gordon SR, Sutton JE, Srivastava A, Smith KD, Gardner TB, Korc M, Davis TH, Preis M, Tarczewski SM, Mackenzie TA, Barth RJ Jr. Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma. Ann Oncol. 2012 Nov;23(11):2820-7. Epub 2012 May 9. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==FOLFIRINOX/modified FOLFIRINOX +/- Chemoradiation==
mFOLFIRINOX: modified FOLinic acid (Leucovorin), Fluorouracil, IRINotecan, OXaliplatin
===Protocol===
Study 	Dates of enrollment	Evidence
Murphy et al. 2018 (MGH 11-328)	2012-2016 	Phase 2
Note: FOLFIRINOX should be limited to those with ECOG 0-1. Amendment after first 6 patients were enrolled increased neoadjuvant cycles from 4 to 8 if no progression was detected on restaging CT
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given second
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given fourth (total dose per cycle: 2800 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV over 90 minutes once on day 1, given third with the last 90 minutes of leucovorin; that is, irinotecan starts 30 minutes after the start of leucovorin
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first
====Supportive therapy====
*Pegfilgrastim (Neulasta) 6 mg SC once on day 4
14-day cycle for 4 to 8 cycles, followed by restaging with CT scan. If tumor was resectable (no vascular involvement), they received short-course proton chemoradiotherapy:
====Chemotherapy====
*Capecitabine (Xeloda) 825 mg/m2 PO twice per day, Monday – Friday for 2 weeks
====Radiotherapy====
*Proton radiotherapy of 2500 cGyE in 5 treatments OR Intensity modulated radiotherapy (IMRT) of 3000 cGy in 10 fractions
One course
===References===
#MGH 11-328: Murphy JE, Wo JY, Ryan DP, Jiang W, Yeap BY, Drapek LC, Blaszkowsky LS, Kwak EL, Allen JN, Clark JW, Faris JE, Zhu AX, Goyal L, Lillemoe KD, DeLaney TF, Fernández-Del Castillo C, Ferrone CR, Hong TS. Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial. JAMA Oncol. 2018 Jul 1;4(7):963-969. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01591733
==mFOLFIRINOX==
mFOLFIRINOX: modified FOLinic acid (Leucovorin), Fluorouracil, IRINotecan, OXaliplatin
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Awaiting publication (Alliance A021501)	2016-2020 	Randomized Phase 2	 	
Hewitt et al. 2022 (PILLAR) 	2013-05 to 2015-12 	Phase 3 (C) 	1a. mFOLFIRINOX & Algenpantucel-L1b. Gemcitabine, nab-Paclitaxel, Algenpantucel-L	Did not meet primary endpoint of OSMedian OS: 14.9 vs 14.3 mo(HR 0.98, 95% CI 0.63-1.52)
Note: comparison in Alliance A021501 was to historic control.
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1
*Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1
*Irinotecan (Camptosar) 180 mg/m2 IV over 90 minutes once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
14-day cycle for varying durations: 5 cycles (PILLAR); 8 cycles (Alliance A021501)
====Subsequent treatment====
*Alliance A021501: Pancreatectomy, then adjuvant mFOLFOX6 x 4
*PILLAR: Chemoradiation
===Regimen variant #2===
Study 	Dates of enrollment	Evidence
Hosein et al. 2012	2008-05 to 2011-05 	Retrospective
Note: Protocol followed "per ACCORD-11 trial."
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
====Supportive therapy====
*Filgrastim (Neupogen) was given at the discretion of the treating physician
14-day cycle until maximum response or intolerance
====Subsequent treatment====
*Hosein et al. 2012, resectable patients by imaging criteria were offered: Surgery, then gemcitabine & RT consolidation
*Hosein et al. 2012, unresectable patients were offered: Definitive Gemcitabine & RT
===References===
#PILLAR: Hewitt DB, Nissen N, Hatoum H, Musher B, Seng J, Coveler AL, Al-Rajabi R, Yeo CJ, Leiby B, Banks J, Balducci L, Vaccaro G, LoConte N, George TJ, Brenner W, Elquza E, Vahanian N, Rossi G, Kennedy E, Link C, Lavu H. A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer. Ann Surg. 2022 Jan 1;275(1):45-53. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01836432
#Retrospective: Hosein PJ, Macintyre J, Kawamura C, Maldonado JC, Ernani V, Loaiza-Bonilla A, Narayanan G, Ribeiro A, Portelance L, Merchan JR, Levi JU, Rocha-Lima CM. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012 May 29;12:199. link to original article link to PMC article EuroPMC
#Alliance A021501: NCT02839343
==mFOLFIRINOX (no folinic acid)==
mFOLFIRINOX: modified FOLinic acid (Leucovorin), Fluorouracil, IRINotecan, OXaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence
Blazer et al. 2014	2011-01 to 2013-08 	Retrospective
====Chemotherapy====
*Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1
*Irinotecan (Camptosar) 165 mg/m2 IV over 90 minutes once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 to 4 hours once on day 1
====Supportive therapy====
*Pegfilgrastim (Neulasta) 6 mg SC once on day 4
14-day cycle for 4 to 8 cycles, followed by complete restaging
====Subsequent treatment====
*Blazer et al. 2014, resectable: Pancreatectomy
*Blazer et al. 2014, tumor localized but still not resectable: Definitive Gemcitabine & RT
===References===
#Retrospective: Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, Wuthrick E, Williams TM, Reardon J, Christopher Ellison E, Bloomston M, Bekaii-Saab T. Neoadjuvant Modified (m) FOLFIRINOX for Locally Advanced Unresectable (LAPC) and Borderline Resectable (BRPC) Adenocarcinoma of the Pancreas. Ann Surg Oncol. 2015 Apr;22(4):1153-9. Epub 2014 Oct 31. link to original article link to PMC article EuroPMC
=Induction therapy for locally advanced disease, unresectable=
==Capecitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Cartwright et al. 2002	1998-1999 	Phase 2
====Chemotherapy====
*Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for up to 18 cycles (1 year)
===References===
#Cartwright TH, Cohn A, Varkey JA, Chen YM, Szatrowski TP, Cox JV, Schulz JJ. Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol. 2002 Jan 1;20(1):160-4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Erlotinib & Gemcitabine==
===Regimen variant #1, Gem 3 out of 4 weeks x 4===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hammel et al. 2016 (GERCOR LAP07)	2008-2011 	Phase 3 (E-esc)	See link 	See link
====Targeted therapy====
*Erlotinib (Tarceva) 100 mg PO once per day on days 1 to 28
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 4 cycles
====Subsequent treatment====
*GERCOR LAP07, patients without progression: Erlotinib & Gemcitabine x 2 (6 total) versus Capecitabine, Erlotinib, RT consolidation
===Regimen variant #2, Gem 3 out of 4 weeks x 6===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hammel et al. 2016 (GERCOR LAP07)	2008-2011 	Phase 3 (E-esc)	See link 	See link
Note: it is not clear from the protocol whether erlotinib is continued beyond the end of chemotherapy.
====Targeted therapy====
*Erlotinib (Tarceva) as follows:
**Cycles 1 to 4: 100 mg PO once per day on days 1 to 28
**Cycles 5 & 6: 150 mg PO once per day on days 1 to 28
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 6 cycles
===Regimen variant #3, gemcitabine lead-in, erlotinib 100 mg/day===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Moore et al. 2007 (NCIC-CTG PA.3)	2001-2003 	Phase 3 (E-RT-esc)	Gemcitabine	Seems to have longer OS (primary endpoint)Median OS: 6.2 vs 5.9 mo(HR 0.82, 95% CI 0.69-0.99)
====Targeted therapy====
*Erlotinib (Tarceva) as follows:
**Cycle 1: 100 mg PO once per day on days 1 to 56
**Cycle 2 onwards: 100 mg PO once per day on days 1 to 28
====Chemotherapy====
*Gemcitabine (Gemzar) as follows:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
**Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
8-week course, then 28-day cycles
===Regimen variant #4, gemcitabine lead-in, erlotinib 150 mg/day===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Moore et al. 2007 (NCIC-CTG PA.3)	2001-2003 	Phase 3 (E-RT-esc)	Gemcitabine	Not reported
Note: due to low accrual, the efficacy of this arm could not be determined.
====Targeted therapy====
*Erlotinib (Tarceva) as follows:
**Cycle 1: 150 mg PO once per day on days 1 to 56
**Cycle 2 onwards: 150 mg PO once per day on days 1 to 28
====Chemotherapy====
*Gemcitabine (Gemzar) as follows:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
**Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
8-week course, then 28-day cycles
===References===
#NCIC-CTG PA.3: Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. Epub 2007 Apr 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00026338
#GERCOR LAP07: Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; GERCOR. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00634725
==Fluorouracil & RT==
Fluorouracil & RT: Fluorouracil & Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Moertel et al. 1981 	Not reported 	Phase 3 (E-esc)	RT 	Longer OS
Herman et al. 2013 (GV-001.004)	2005-2010 	Phase 3 (C) 	Fluorouracil & RT with TNFerade	Did not meet primary endpoint of OSMedian OS: 10 vs 10 mo(HR 0.90, 95% CI 0.66-1.22)
Note: treatment is assumed to start on a Monday.
====Chemotherapy====
*Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 22, 29 (total dose: 5000 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy: 180 cGy fractions x 25 fractions, for a total dose of 4500 cGy, followed by 180 cGy x 3 fractions boost to the tumor bed (total dose of 5040 cGy)
5.5-week course
====Subsequent treatment====
*GV-001.004: Gemcitabine or Erlotinib & Gemcitabine maintenance, starting four weeks after chemoradiotherapy
===References===
#Moertel CG, Frytak S, Hahn RG, O'Connell MJ, Reitemeier RJ, Rubin J, Schutt AJ, Weiland LH, Childs DS, Holbrook MA, Lavin PT, Livstone E, Spiro H, Knowlton A, Kalser M, Barkin J, Lessner H, Mann-Kaplan R, Ramming K, Douglas HO Jr, Thomas P, Nave H, Bateman J, Lokich J, Brooks J, Chaffey J, Corson JM, Zamcheck N, Novak JW; Gastrointestinal Tumor Study Group. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer. 1981 Oct 15;48(8):1705-10. link to original article EuroPMC
#GV-001.004: Herman JM, Wild AT, Wang H, Tran PT, Chang KJ, Taylor GE, Donehower RC, Pawlik TM, Ziegler MA, Cai H, Savage DT, Canto MI, Klapman J, Reid T, Shah RJ, Hoffe SE, Rosemurgy A, Wolfgang CL, Laheru DA. Randomized phase III multi-institutional study of TNFerade biologic with fluorouracil and radiotherapy for locally advanced pancreatic cancer: final results. J Clin Oncol. 2013 Mar 1;31(7):886-94. Epub 2013 Jan 22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00051467
==Gemcitabine monotherapy==
===Regimen variant #1, 3 out of 4 weeks x 4===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hammel et al. 2016 (GERCOR LAP07)	2008-2011 	Phase 3 (C)	See link 	See link
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 4 cycles
====Subsequent treatment====
*GERCOR LAP07, patients without progression: Gemcitabine x 2 (6 total) versus Capecitabine & RT consolidation
===Regimen variant #2, 3 out of 4 weeks x 6===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hammel et al. 2016 (GERCOR LAP07)	2008-2011 	Phase 3 (C)	See link 	See link
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 6 cycles
===Regimen variant #3, 8-week lead-in ("Burris regimen")===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cantore et al. 2004 	1997-2001 	Phase 3 (C) 	Intraarterial FLEC 	Seems to have shorter OS (primary endpoint)Median OS: 5.8 vs 7.9 mo(HR not reported)
Chauffert et al. 2008 (FFCD/SFRO 2000-01)	2000-2005 	Phase 3 (E-de-esc)	CF & RT, then Gemcitabine	Seems to have longer OS (primary endpoint)Median OS: 13 vs 8.6 mo(aHR 0.54, 95% CI 0.31-0.96)
Louvet et al. 2005 	2001-2003 	Phase 3 (C) 	GemOx 	Seems to have shorter PFS (secondary endpoint)Median PFS: 3.7 vs 5.8 mo(HR 1.28, 95% CI 1.01-1.69)
Loehrer et al. 2011 (ECOG E4201) 	2003-2005 	Phase 3 (C) 	Gemcitabine & RT 	Seems to have shorter OSMedian OS: 9.2 vs 11.1 mo(HR not reported)
====Chemotherapy====
*Gemcitabine (Gemzar) as follows:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
**Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
8-week course, then 28-day cycles
====Subsequent treatment====
*Louvet et al. 2005: 5-FU & RT consolidation was recommended but not mandated
===Regimen variant #4, 7-week lead-in===
Study 	Dates of enrollment	Evidence
Epelbaum et al. 2002	1997-1999 	Phase 2
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
7-week course
====Subsequent treatment====
*Epelbaum et al. 2002, patients with both a clinical benefit response (CBR) and stable disease or better on imaging: Gemcitabine & RT consolidation, then Gemcitabine maintenance
===References===
#Epelbaum R, Rosenblatt E, Nasrallah S, Faraggi D, Gaitini D, Mizrahi S, Kuten A. Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J Surg Oncol. 2002 Nov;81(3):138-43. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Cantore M, Fiorentini G, Luppi G, Rosati G, Caudana R, Piazza E, Comella G, Ceravolo C, Miserocchi L, Mambrini A, Del Freo A, Zamagni D, Rabbi C, Marangolo M. Gemcitabine versus FLEC regimen given intra-arterially to patients with unresectable pancreatic cancer: a prospective, randomized phase III trial of the Italian Society for Integrated Locoregional Therapy in Oncology. J Chemother. 2004 Dec;16(6):589-94. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A; GERCOR; GISCAD. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005 May 20;23(15):3509-16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#FFCD/SFRO 2000-01: Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouché O, Bosset JF, Aparicio T, Mineur L, Azzedine A, Hammel P, Butel J, Stremsdoerfer N, Maingon P, Bedenne L. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer: definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol. 2008 Sep;19(9):1592-9. Epub 2008 May 7. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00416507
#ECOG E4201: Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011 Nov 1;29(31):4105-12. Epub 2011 Oct 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00057876
#GERCOR LAP07: Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; GERCOR. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00634725
#AB12005: NCT03766295
==Gemcitabine & RT==
Gemcitabine & RT: Gemcitabine & Radiation Therapy
===Regimen variant #1, 600 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cardenes et al. 2011 	2001-2003 	Phase 2 	 	
Loehrer et al. 2011 (ECOG E4201)	2003-2005 	Phase 3 (E-esc)	Gemcitabine	Seems to have longer OS (primary endpoint)Median OS: 11.1 vs 9.2 mo(HR not reported)
====Chemotherapy, induction====
*Gemcitabine (Gemzar) 600 mg/m2 IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29
====Radiotherapy====
*Concurrent radiation therapy, 180 cGy per fraction x 28 fractions, total dose of 5040 cGy
10-week course
====Subsequent treatment====
*Gemcitabine consolidation
===Regimen variant #2, 400 mg/m2===
Study 	Dates of enrollment	Evidence
Epelbaum et al. 2002	1997-1999 	Phase 2
====Preceding treatment====
*Gemcitabine induction
====Chemotherapy====
*Gemcitabine (Gemzar) 400 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 29, 36, 43
====Radiotherapy====
*Concurrent radiation therapy 180 cGy x 28 fractions, total dose of 5040 cGy
5.5-week course
====Subsequent treatment====
*Gemcitabine maintenance
===References===
#Epelbaum R, Rosenblatt E, Nasrallah S, Faraggi D, Gaitini D, Mizrahi S, Kuten A. Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J Surg Oncol. 2002 Nov;81(3):138-43. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Cardenes HR, Moore AM, Johnson CS, Yu M, Helft P, Chiorean EG, Vinson J, Howard TJ, Stephens AW, Tai DF, Loehrer PJ Sr; Hoosier Oncology Group. A phase II study of gemcitabine in combination with radiation therapy in patients with localized, unresectable, pancreatic cancer: a Hoosier Oncology Group study. Am J Clin Oncol. 2011 Oct;34(5):460-5. link to original article EuroPMC
#ECOG E4201: Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011 Nov 1;29(31):4105-12. Epub 2011 Oct 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00057876
==GemOx==
GemOx: Gemcitabine, Oxaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Louvet et al. 2005	2001-2003 	Phase 3 (E-esc)	Gemcitabine	Seems to have longer PFS (secondary endpoint)Median PFS: 5.8 vs 3.7 mo(HR 0.78, 95% CI 0.59-0.99)
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 100 minutes once on day 1
*Oxaliplatin (Eloxatin) 100 mg/m2 IV over 2 hours once on day 2
14-day cycle for at least 6 cycles
====Subsequent treatment====
*Subsequent chemoradiotherapy (4500 cGy in 25 fractions for 5 weeks, associated with a daily FU 250 mg/m2 continuous infusion, and a boost of 1000 cGy in 8 fractions restricted to the initial tumor volume) was recommended but not mandated.
===References===
#Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A; GERCOR; GISCAD. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005 May 20;23(15):3509-16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Radiation therapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cohen et al. 2005 (ECOG E8282)	1983-1989 	Phase 3 (C)	5-FU, MMC, RT	Did not meet efficacy endpoints
====Radiotherapy====
*External beam radiotherapy
===References===
#ECOG E8282: Cohen SJ, Dobelbower R Jr, Lipsitz S, Catalano PJ, Sischy B, Smith TJ, Haller DG; ECOG. A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282. Int J Radiat Oncol Biol Phys. 2005 Aug 1;62(5):1345-50. link to original article EuroPMC
=Consolidation therapy for locally advanced disease=
==Gemcitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Loehrer et al. 2011 (ECOG E4201)	2003-2005 	Non-randomized part of phase 3 RCT
====Preceding treatment====
*Definitive Gemcitabine & RT
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for up to 5 cycles
===References===
#ECOG E4201: Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011 Nov 1;29(31):4105-12. Epub 2011 Oct 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00057876
=Maintenance therapy for locally advanced disease=
==Gemcitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Epelbaum et al. 2002	1997-1999 	Phase 2
====Preceding treatment====
*Definitive Gemcitabine & RT
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
===References===
#Epelbaum R, Rosenblatt E, Nasrallah S, Faraggi D, Gaitini D, Mizrahi S, Kuten A. Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J Surg Oncol. 2002 Nov;81(3):138-43. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Metastatic disease, first-line=
==Capecitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Cartwright et al. 2002	1998-1999 	Phase 2
====Chemotherapy====
*Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for up to 18 cycles (1 year)
===References===
#Cartwright TH, Cohn A, Varkey JA, Chen YM, Szatrowski TP, Cox JV, Schulz JJ. Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol. 2002 Jan 1;20(1):160-4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Capecitabine & Gemcitabine==
GemCap: Gemcitabine & Capecitabine
GEM-CAP: GEMcitabine & CAPecitabine
===Regimen variant #1, q4wk x 6===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Middleton et al. 2014 (TeloVac)	2007-2011 	Phase 3 (C)	1. GemCap & Tertomotide 	Did not meet primary endpoint of OSMedian OS: 7.9 vs 8.4 mo(HR 0.95, 98.25% CI 0.85-1.29)
Middleton et al. 2014 (TeloVac)	2007-2011 	Phase 3 (C)	2. GemCap x 2, then Tertomotide	Might have longer OSMedian OS: 7.9 vs 6.9 mo(HR 0.9845, 98.25% CI 0.67-1.03)
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Capecitabine (Xeloda) 830 mg/m2 PO twice per day on days 1 to 21
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 6 cycles
===Regimen variant #2, q4wk indefinite===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Lee et al. 2017 	2007-2011 	Phase 3 (E-esc)	Gemcitabine 	Might have longer OS (primary endpoint)Median OS: 10.3 vs 7.5 mo(HR 0.82, 95% CI 0.67-1.01)
Jo et al. 2023 (KG 4/2015)	2015-11 to 2020-04 	Phase 3 (C) 	GemCap & Tertomotide	Seems to have shorter OS (primary endpoint)Median OS: 7.5 vs 11.3 mo(HR not reported)
====Chemotherapy====
*Capecitabine (Xeloda) 830 mg/m2 PO twice per day on days 1 to 21
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
===Regimen variant #3, induction followed by maintenance===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cunningham et al. 2009 (CRUK GEM-CAP)	2002-2005 	Phase 3 (E-esc)	Gemcitabine	Might have longer OS (primary endpoint)Median OS: 7.1 vs 6.2 mo(HR 0.86, 95% CI 0.72-1.02)
====Chemotherapy====
*Capecitabine (Xeloda) as follows:
**Cycle 1: 830 mg/m2 PO twice per day on days 1 to 21, 29 to 49
**Cycle 2 onwards: 830 mg/m2 PO twice per day on days 1 to 21
*Gemcitabine (Gemzar) as follows:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
**Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
8-week course, then 28-day cycles
===Regimen variant #4, q3wk x 8===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Herrmann et al. 2007 (SAKK 44/00-CECOG/PAN.1.3.001)	2001-2004 	Phase 3 (E-esc)	Gemcitabine	Did not meet primary endpoint of OS50%Median OS: 8.4 vs 7.2 mo(HR 0.87, 95% CI 0.67-1.10)
====Chemotherapy====
*Capecitabine (Xeloda) 650 mg/m2 PO twice per day on days 1 to 14
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycle for up to 8 cycles
===References===
#SAKK 44/00-CECOG/PAN.1.3.001: Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W; Swiss Group for Clinical Cancer Research; Central European Cooperative Oncology Group. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol. 2007 Jun 1;25(16):2212-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00030732
##CBR/QoL analysis: Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Herrmann R; Central European Cooperative Oncology Group. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol. 2008 Aug 1;26(22):3695-701. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#CRUK GEM-CAP: Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009 Nov 20;27(33):5513-8. Epub 2009 Oct 26. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00032175
#TeloVac: Middleton G, Silcocks P, Cox T, Valle J, Wadsley J, Propper D, Coxon F, Ross P, Madhusudan S, Roques T, Cunningham D, Falk S, Wadd N, Harrison M, Corrie P, Iveson T, Robinson A, McAdam K, Eatock M, Evans J, Archer C, Hickish T, Garcia-Alonso A, Nicolson M, Steward W, Anthoney A, Greenhalf W, Shaw V, Costello E, Naisbitt D, Rawcliffe C, Nanson G, Neoptolemos J. Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial. Lancet Oncol. 2014 Jul;15(8):829-40. Epub 2014 Jun 19. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00425360
#Lee HS, Chung MJ, Park JY, Bang S, Park SW, Kim HG, Noh MH, Lee SH, Kim YT, Kim HJ, Kim CD, Lee DK, Cho KB, Cho CM, Moon JH, Kim DU, Kang DH, Cheon YK, Choi HS, Kim TH, Kim JK, Moon J, Shin HJ, Song SY; Korean Society of Gastrointestinal Cancer. A randomized, multicenter, phase III study of gemcitabine combined with capecitabine versus gemcitabine alone as first-line chemotherapy for advanced pancreatic cancer in South Korea. Medicine (Baltimore). 2017 Jan;96(1):e5702. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
#KG 4/2015: Jo JH, Kim YT, Choi HS, Kim HG, Lee HS, Choi YW, Kim DU, Lee KH, Kim EJ, Han JH, Lee SO, Park CH, Choi EK, Kim JW, Cho JY, Lee WJ, Moon HR, Park MS, Kim S, Song SY. Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomised, Phase 3 trial. Br J Cancer. 2024 Jan;130(1):43-52. Epub 2023 Oct 30. Erratum in: Br J Cancer. 2023 Dec 4. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02854072
==Cisplatin & Gemcitabine (GC)==
===Regimen variant #1, 25/1000, weekly dosing, limited duration===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Colucci et al. 2002	Not reported 	Phase 3 (E-esc)	Gemcitabine	Seems to have longer TTP (primary endpoint)Median TTP: 20 vs 8 weeks(HR 0.67, 95% CI 0.45-1.00)
Note: Cisplatin is not given on day 22 of the first cycle; otherwise, the schedule is identical to the schedule for gemcitabine. 95% CI was not reported in the manuscript and is calculated using the Wald P-value assumption.
====Chemotherapy====
*Cisplatin (Platinol) as follows, given first, 60 minutes prior to gemcitabine:
**Cycle 1: 25 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 29, 36, 43
**Cycles 2 & 3: 25 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
*Gemcitabine (Gemzar) as follows, given second:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
**Cycles 2 & 3: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
8-week course, then 28-day cycle for 2 cycles
===Regimen variant #2, 25/1000, weekly dosing===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Colucci et al. 2010 (GIP-1)	2002-2007 	Phase 3 (E-esc)	Gemcitabine	Did not meet primary endpoint of OSMedian OS: 7.2 vs 8.3 mo(HR 1.10, 95% CI 0.89-1.35)
Note: Cisplatin is not given on day 22 of the first cycle; otherwise, the schedule is identical to the schedule for gemcitabine.
====Chemotherapy====
*Cisplatin (Platinol) as follows, given first, 60 minutes prior to gemcitabine:
**Cycle 1: 25 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 29, 36, 43
**Cycle 2 onwards: 25 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
*Gemcitabine (Gemzar) as follows, given second:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
**Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
8-week course, then 28-day cycles
===Regimen variant #3, 35/1000, 2 out of 3 weeks===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cascinu et al. 2008 (SPaCe-01)	2005-2006 	Randomized Phase 2 (C)	GC & Cetuximab	Did not meet primary endpoint of ORR
====Chemotherapy====
*Cisplatin (Platinol) 35 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
21-day cycles
===Regimen variant #4, 50/1000, bi-weekly dosing===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Heinemann et al. 2006	1997-2002 	Phase 3 (E-esc)	Gemcitabine	Did not meet primary endpoint of OSMedian OS: 7.5 vs 6 mo(aHR 0.92, 95% CI 0.66-1.28)
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV over 60 minutes once per day on days 1 & 15
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 15
28-day cycles
===References===
#Colucci G, Giuliani F, Gebbia V, Biglietto M, Rabitti P, Uomo G, Cigolari S, Testa A, Maiello E, Lopez M. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell'Italia Meridionale. Cancer. 2002 Feb 15;94(4):902-10. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schönekäs H, Rost A, Neuhaus H, Haag C, Clemens M, Heinrich B, Vehling-Kaiser U, Fuchs M, Fleckenstein D, Gesierich W, Uthgenannt D, Einsele H, Holstege A, Hinke A, Schalhorn A, Wilkowski R. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol. 2006 Aug 20;24(24):3946-52. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#SPaCe-01: Cascinu S, Berardi R, Labianca R, Siena S, Falcone A, Aitini E, Barni S, Di Costanzo F, Dapretto E, Tonini G, Pierantoni C, Artale S, Rota S, Floriani I, Scartozzi M, Zaniboni A; Italian Group for the Study of Digestive Tract Cancer. Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer: a randomised, multicentre, phase II trial. Lancet Oncol. 2008 Jan;9(1):39-44. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00536614
#GIP-1: Colucci G, Labianca R, Di Costanzo F, Gebbia V, Cartenì G, Massidda B, Dapretto E, Manzione L, Piazza E, Sannicolò M, Ciaparrone M, Cavanna L, Giuliani F, Maiello E, Testa A, Pederzoli P, Falconi M, Gallo C, Di Maio M, Perrone F; GOIM; GISCAD; GOIRC. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol. 2010 Apr 1;28(10):1645-51. Epub 2010 Mar 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00813696
==Erlotinib & Gemcitabine==
===Regimen variant #1, no gemcitabine lead-in===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kordes et al. 2015 (AMCmedonc10/003)	2010-2014 	Randomized Phase 2 (C)	Erlotinib, Gemcitabine, Metformin	Did not meet primary endpoint of OS6
====Targeted therapy====
*Erlotinib (Tarceva) 100 mg PO once per day on days 1 to 28
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
===Regimen variant #2, gemcitabine lead-in, erlotinib 100 mg/day===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Moore et al. 2007 (NCIC-CTG PA.3)	2001-2003 	Phase 3 (E-RT-esc)	Gemcitabine 	Seems to have longer OS (primary endpoint)Median OS: 6.2 vs 5.9 mo(HR 0.82, 95% CI 0.69-0.99)
Van Cutsem et al. 2009 (BO17706) 	2005-07 to 2006-09 	Phase 3 (C) 	Erlotinib, Gemcitabine, Bevacizumab	Did not meet primary endpoint of OSMedian OS: 6 vs 7.1 mo(HR 1.12, 95% CI 0.93-1.35)
====Targeted therapy====
*Erlotinib (Tarceva) as follows:
**Cycle 1: 100 mg PO once per day on days 1 to 56
**Cycle 2 onwards: 100 mg PO once per day on days 1 to 28
====Chemotherapy====
*Gemcitabine (Gemzar) as follows:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
**Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
8-week course, then 28-day cycles
===Regimen variant #3, gemcitabine lead-in, erlotinib 150 mg/day===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Moore et al. 2007 (NCIC-CTG PA.3) 	2001-2003 	Phase 3 (E-RT-esc)	Gemcitabine 	Not reported
Heinemann et al. 2012 (AIO-PK0104)	2006-2008 	Phase 3 (C) 	Capecitabine & Erlotinib	Inconclusive whether non-inferior TTF2 (primary endpoint)TTF2: 4.2 vs 4.2 mo
Note: due to low accrual in NCIC-CTG PA.3, the efficacy of this arm could not be determined.
====Targeted therapy====
*Erlotinib (Tarceva) as follows:
**Cycle 1: 150 mg PO once per day on days 1 to 56
**Cycle 2 onwards: 150 mg PO once per day on days 1 to 28
====Chemotherapy====
*Gemcitabine (Gemzar) as follows:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
**Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
8-week course, then 28-day cycles
===References===
#NCIC-CTG PA.3: Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. Epub 2007 Apr 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00026338
#BO17706: Van Cutsem E, Vervenne WL, Bennouna J, Humblet Y, Gill S, Van Laethem JL, Verslype C, Scheithauer W, Shang A, Cosaert J, Moore MJ. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol. 2009 May 1;27(13):2231-7. Epub 2009 Mar 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01214720
#AIO-PK0104: Heinemann V, Vehling-Kaiser U, Waldschmidt D, Kettner E, Märten A, Winkelmann C, Klein S, Kojouharoff G, Gauler TC, von Weikersthal LF, Clemens MR, Geissler M, Greten TF, Hegewisch-Becker S, Rubanov O, Baake G, Höhler T, Ko YD, Jung A, Neugebauer S, Boeck S. Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO-PK0104). Gut. 2013 May;62(5):751-9. Epub 2012 Jul 7. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00440167
#AMCmedonc10/003: Kordes S, Pollak MN, Zwinderman AH, Mathôt RA, Weterman MJ, Beeker A, Punt CJ, Richel DJ, Wilmink JW. Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol. 2015 Jul;16(7):839-47. Epub 2015 Jun 8. link to original articledosing details in abstract have been reviewed by our editors EuroPMC NCT01210911
==Fluorouracil monotherapy==
===Regimen variant #1, 300 mg/m2/day PVI===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Maisey et al. 2002	1994-2000 	Phase 3 (C)	5-FU & Mitomycin	Seems to have lower ORR
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Fluorouracil (5-FU) 300 mg/m2/day IV continuous infusion
Up to 24-week course
===Regimen variant #2, 500 mg/m2 intermittent 28-day cycles===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Ducreux et al. 2002 (EORTC 05962)	1992-1998 	Phase 3 (C)	CF 	Did not meet primary endpoint of OS
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 to 5
28-day cycles
===Regimen variant #3, 500 mg/m2 intermittent with spacing===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cullinan et al. 1985	Not reported 	Phase 3 (E-de-esc)	1. FA2. FAM 	Did not meet primary endpoint of OS
Cullinan et al. 1990	Not reported 	Phase 3 (C) 	1. Mallinson regimen2. FAP	Did not meet primary endpoint of OS
Note: This was an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.
====Chemotherapy====
*Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 to 5
28-day cycle for 2 cycles, then 35-day cycles
===Regimen variant #4, 500 mg/m2 intermittent 35-day cycles===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Burch et al. 2000	Not reported 	Phase 3 (C)	Octreotide	Did not meet primary endpoint of OS
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 to 5
35-day cycles
===Regimen variant #5, 600 mg/m2 weekly===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Burris et al. 1997	1992-1994 	Phase 3 (C)	Gemcitabine	Shorter OS (secondary endpoint)Median OS: 4.41 vs 5.65 mo(HR not reported)
Note: this variant is here for historical reference purposes, only. To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1, 8, 15, 22
28-day cycles
===References===
#Cullinan SA, Moertel CG, Fleming TR, Rubin JR, Krook JE, Everson LK, Windschitl HE, Twito DI, Marschke RF, Foley JF, Pfeifle DM, Barlow JF. A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma: fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA. 1985 Apr 12;253(14):2061-7. link to original article EuroPMC
#Cullinan S, Moertel CG, Wieand HS, Schutt AJ, Krook JE, Foley JF, Norris BD, Kardinal CG, Tschetter LK, Barlow JF. A phase III trial on the therapy of advanced pancreatic carcinoma: evaluations of the Mallinson regimen and combined 5-fluorouracil, doxorubicin, and cisplatin. Cancer. 1990 May 15;65(10):2207-12. link to original article EuroPMC
#Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Burch PA, Block M, Schroeder G, Kugler JW, Sargent DJ, Braich TA, Mailliard JA, Michalak JC, Hatfield AK, Wright K, Kuross SA; NCCTG. Phase III evaluation of octreotide versus chemotherapy with 5-fluorouracil or 5-fluorouracil plus leucovorin in advanced exocrine pancreatic cancer: a North Central Cancer Treatment Group study. Clin Cancer Res. 2000 Sep;6(9):3486-92. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Maisey N, Chau I, Cunningham D, Norman A, Seymour M, Hickish T, Iveson T, O'Brien M, Tebbutt N, Harrington A, Hill M. Multicenter randomized phase III trial comparing protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin in inoperable pancreatic cancer. J Clin Oncol. 2002 Jul 15;20(14):3130-6. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#EORTC 05962: Ducreux M, Rougier P, Pignon JP, Douillard JY, Seitz JF, Bugat R, Bosset JF, Merouche Y, Raoul JL, Ychou M, Adenis A, Berthault-Cvitkovic F, Luboinski M; Groupe Digestif of the Fédération Nationale des Centres de Lutte Contre le Cancer Digestif. A randomised trial comparing 5-FU with 5-FU plus cisplatin in advanced pancreatic carcinoma. Ann Oncol. 2002 Aug;13(8):1185-91. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003029
==FOLFIRINOX==
FOLFIRINOX: FOLinic acid (Leucovorin), Fluorouracil, IRINotecan, OXaliplatin
FFX: Folinic acid (Leucovorin), Fluorouracil, Irinotecan, Oxaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Conroy et al. 2011 (PRODIGE 4/ACCORD 11)	2005-2009 	Phase 3 (E-esc)	Gemcitabine 	Longer OS (primary endpoint)Median OS: 11.1 vs 6.8 mo(HR 0.57, 95% CI 0.45-0.73) 	Better QoL by EORTC QLQ-C30
Philip et al. 2024 (AVENGER 500) 	2018-12 to 2020-08 	Phase 3 (C) 	mFOLFIRINOX & Devimistat	Did not meet primary endpoint of OSMedian OS: 11.73 vs 11.1 mo(HR 1.05, 95% CI 0.85-1.30)	
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given second
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given fourth (total dose per cycle: 2800 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV over 90 minutes once on day 1, given third with the last 90 minutes of leucovorin; that is, irinotecan starts 30 minutes after the start of leucovorin
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first
14-day cycles
===References===
#PRODIGE 4/ACCORD 11: Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00112658
##HRQoL analysis: Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Boige V, Bérille J, Conroy T. Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol. 2013 Jan 1;31(1):23-9. Epub 2012 Dec 3. link to original article EuroPMC
#AVENGER 500: Philip PA, Sahai V, Bahary N, Mahipal A, Kasi A, Rocha Lima CMS, Alistar AT, Oberstein PE, Golan T, Metges JP, Lacy J, Fountzilas C, Lopez CD, Ducreux M, Hammel P, Salem M, Bajor D, Benson AB, Luther S, Pardee T, Van Cutsem E. Devimistat (CPI-613) With Modified Fluorouarcil, Oxaliplatin, Irinotecan, and Leucovorin (FFX) Versus FFX for Patients With Metastatic Adenocarcinoma of the Pancreas: The Phase III AVENGER 500 Study. J Clin Oncol. 2024 Nov;42(31):3692-3701. Epub 2024 Aug 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03504423
==Gemcitabine monotherapy==
===Regimen variant #1, 900 mg/m2, 3 out of 4 weeks===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Stathopoulos et al. 2006	2001-2005 	Phase 3 (C)	IG 	Did not meet primary endpoint of OSMedian OS: 6.5 vs 6.4 mo(HR not reported)
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Gemcitabine (Gemzar) 900 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
===Regimen variant #2, 1000 mg/m2, 8-week lead-in ("Burris regimen")===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Burris et al. 1997 	1992-1994 	Phase 3 (E-RT-switch-ic)	5-FU 	Longer OS (secondary endpoint)Median OS: 5.65 vs 4.41 mo(HR not reported)Higher clinical benefit response (primary endpoint)
Bramhall et al. 2001 	1996-05 to 1997-09 	Phase 3 (C) 	1. Marimistat; 10 mg/day2. Marimistat; 20 mg/day3. Marimistat; 50 mg/day	Did not meet primary endpoint of OS
Bramhall et al. 2002 	1996-05 to 1997-09 	Randomized (C) 	Gemcitabine & Marimastat 	Did not meet primary endpoint of OSMedian OS: 164 vs 165.5 days
Colucci et al. 2002 	Not reported 	Phase 3 (C) 	GC 	Seems to have shorter TTP (primary endpoint)Median TTP: 8 vs 20 weeks(HR 1.49, 95% CI 1.00-2.22)
Moore et al. 2003 (NCIC-CTG PA.1) 	1997-1999 	Phase 3 (C) 	Tanomastat 	Longer OS (primary endpoint)Median OS: 6.59 vs 3.74 mo(aHR 0.57, 95% CI 0.445-0.74)
Van Cutsem et al. 2004 (CR003976) 	1999-2001 	Phase 3 (C) 	Gemcitabine & Tipifarnib 	Did not meet primary endpoint of OSMedian OS: 182 vs 193 d
Rocha Lima et al. 2004 	2000-02-10 to 2001-12-28	Phase 3 (C) 	IG 	Did not meet primary endpoint of OSMedian OS: 6.6 vs 6.3 mo(HR not reported)
Reni et al. 2005 	2000-2003 	Phase 3 (C) 	PEFG 	Lower PFS4PFS4: 28% vs 60%(HR 2.17, 95% CI 1.27-3.85)
Louvet et al. 2005 	2001-2003 	Phase 3 (C) 	GemOx 	Seems to have shorter PFS (secondary endpoint)Median PFS: 3.7 vs 5.8 mo(HR 1.28, 95% CI 1.01-1.69)
Abou-Alfa et al. 2006 (MSKCC 02-011) 	2001-2003 	Phase 3 (C) 	Gemcitabine & Exatecan 	Did not meet primary endpoint of OSMedian OS: 6.2 vs 6.7 mo(HR not reported)
Moore et al. 2007 (NCIC-CTG PA.3) 	2001-2003 	Phase 3 (C) 	Erlotinib & Gemcitabine 	Seems to have shorter OS (primary endpoint)Median OS: 5.9 vs 6.2 mo(HR 1.22, 95% CI 1.01-1.45)
Herrmann et al. 2007 (SAKK 44/00-CECOG/PAN.1.3.001)	2001-2004 	Phase 3 (C) 	GemCap 	Did not meet primary endpoint of OS50%Median OS: 7.2 vs 8.4 mo(HR 1.15, 95% CI 0.91-1.49)
Poplin et al. 2009 (ECOG E6201) 	2003-2005 	Phase 3 (C) 	1. Gemcitabine; fixed dose rate 	Might have shorter OS
Poplin et al. 2009 (ECOG E6201) 	2003-2005 	Phase 3 (C) 	2. GEMOX 	Did not meet primary endpoint of OS
Cunningham et al. 2009 (CRUK GEM-CAP) 	2002-2005 	Phase 3 (C) 	GEM-CAP 	Might have shorter OSMedian OS: 6.2 vs 7.1 mo(HR 1.16, 95% CI 0.98-1.39)
Colucci et al. 2010 (GIP-1) 	2002-2007 	Phase 3 (C) 	GC 	Did not meet primary endpoint of OSMedian OS: 8.3 vs 7.2 mo(HR 0.91, 95% CI 0.74-1.12)
Dahan et al. 2010 (FFCD 0301) 	2003-2006 	Phase 3 (C) 	LV5FU2-CDDP 	Did not meet primary endpoint of OSMedian OS: 8 vs 6.6 mo(HR 0.97, 95% CI 0.73-1.29)
Philip et al. 2010 (SWOG S0205) 	2004-2006 	Phase 3 (C) 	Gemcitabine & Cetuximab 	Did not meet primary endpoint of OSMedian OS: 5.9 vs 6.3 mo(HR 0.94, 95% CI 0.81-1.10)
Conroy et al. 2011 (PRODIGE 4/ACCORD 11) 	2005-2009 	Phase 3 (C) 	FOLFIRINOX 	Shorter OSMedian OS: 6.8 vs 11.1 mo(HR 1.75, 95% CI 1.37-2.22)
Gonçalves et al. 2012 (BAYPAN) 	2006-2009 	Phase 3 (C) 	Gemcitabine & Sorafenib 	Did not meet primary endpoint of PFSMedian PFS: 5.7 vs 3.8 mo(HR 0.96, 95% CI 0.65-1.43)
Rougier et al. 2013 (VANILLA) 	2007-2009 	Phase 3 (C) 	Gemcitabine & Ziv-aflibercept 	Did not meet primary endpoint of OSMedian OS: 7.8 vs 6.5 mo(HR 0.86, 95% CI 0.68-1.09)
Von Hoff et al. 2013 (MPACT) 	2009-2012 	Phase 3 (C) 	Gemcitabine & nab-Paclitaxel 	Shorter OS1Median OS: 6.6 vs 8.7 mo(HR 1.39, 95% CI 1.20-1.61)
Deplanque et al. 2015 (AB07012) 	Not reported 	Phase 3 (C) 	Gemcitabine & Masitinib 	Did not meet primary endpoint of OSMedian OS: 7.1 vs 7.7 mo(HR 1.12, 95% CI 0.88-1.43)
Middleton et al. 2017 (ViP) 	2011-2013 	Randomized Phase 2 (C) 	Gemcitabine & Vandetanib 	Did not meet primary endpoint of OSMedian OS: 8.95 vs 8.8 mo(HR 0.83, 80.8% CI 0.65-1.05)
1Reported efficacy for MPACT is based on the 2015 update.
Note: Colucci et al. 2002 stopped treatment after 3 cycles (16 weeks).
====Chemotherapy====
*Gemcitabine (Gemzar) as follows:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
**Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
8-week course, then 28-day cycles
====Dose and schedule modifications====
*In Burris et al. 1997, patients with grade 2 or lower toxicities could have had gemcitabine dose increased to 1250 mg/m2
===Regimen variant #3, 1000 mg/m2, 3 out of 4 weeks===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Heinemann et al. 2006 	1997-2002 	Phase 3 (C) 	Cisplatin & Gemcitabine 	Did not meet primary endpoint of OSMedian OS: 6 vs 7.5 mo(aHR 1.09, 95% CI 0.78-1.52)
Berlin et al. 2002 (ECOG E2297) 	1998-04 to 1999-11 	Phase 3 (C) 	5-FU & Gemcitabine 	Might have shorter OS (primary endpoint)Median OS: 5.4 vs 6.7 mo(HR not reported)
Oettle et al. 2005 (JMES) 	2001-2003 	Phase 3 (C) 	Gemcitabine & Pemetrexed 	Did not meet primary endpoint of OSMedian OS: 6.3 vs 6.2 mo(HR 1.02, 95% CI 0.85-1.22)
Kindler et al. 2010 (CALGB 80303) 	2004-2006 	Phase 3 (C) 	Gemcitabine & Bevacizumab	Did not meet primary endpoint of OSMedian OS: 5.9 vs 5.8 mo(HR 0.96, 95% CI 0.81-1.14)
Spano et al. 2008 (A4061016) 	2006-01 to 2006-08 	Randomized Phase 2 (C) 	Gemcitabine & Axitinib 	Did not meet primary endpoint of OSMedian OS: 5.6 vs 6.9 mo(sHR 1.41, 95% CI 0.88-2.27)
Kindler et al. 2011 (A4061028) 	2007-07-27 to 2008-10-31	Phase 3 (C) 	Gemcitabine & Axitinib 	Did not meet primary endpoint of OSMedian OS: 8.3 vs 8.5 mo(HR 0.99, 95% CI 0.76-1.27)
Ueno et al. 2013 (GEST) 	2007-2009 	Phase 3 (C) 	1. S-1 	Non-inferior OS
Ueno et al. 2013 (GEST) 	2007-2009 	Phase 3 (C) 	2. Gemcitabine & S-1 	Did not meet primary endpoint of OS
Lee et al. 2017 	2007-2011 	Phase 3 (C) 	GemCap 	Might have shorter OSMedian OS: 7.5 vs 10.3 mo(HR 1.22, 95% CI 0.99-1.49)
Catenacci et al. 2015 (UCCRC-8418)	2010-2012 	Randomized Phase 1b/2 (C)	Gemcitabine & Vismodegib 	Did not meet primary endpoint of PFSMedian PFS: 2.5 vs 4 mo(aHR 1.23, 95% CI 0.83-1.85)
Fuchs et al. 2015 (GAMMA) 	2011-2012 	Randomized Phase 1b/2 (C)	Gemcitabine & Ganitumab 	Did not meet primary endpoint of OSMedian OS: 7.2 vs 7 mo(HR 1.00, 95% CI 0.83-1.22)
O'Neil et al. 2015 (ONTRAC) 	2011-2013 	Phase 2/3 (C) 	Gemcitabine & Rigosertib 	Did not meet primary endpoint of OSMedian OS: 6.4 vs 6.1 mo(HR 0.81, 95% CI 0.55-1.18)
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
===Regimen variant #4, 1000 mg/m2, 7 out of 8 weeks===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Qin et al. 2023 (NOTABLE)	2015-04 to 2021-03 	Phase 3 (C)	Gemcitabine & Nimotuzumab	Seems to have shorter OS (primary endpoint)Median OS: 8.5 vs 10.9 mo(RMST ratio 1.61, 95% CI 1.03-2.50)
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Biomarker eligibility criteria====
*KRAS wild-type
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 29, 36, 42, 49
8-week cycles
===Regimen variant #5, 1000 mg/m2, weekly===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hong et al. 2013 (SMC 2008-07-065)	2008-2012 	Randomized Phase 2 (C)	Gemcitabine & Simvastatin	Did not meet primary endpoint of TTPMedian TTP: 3.6 vs 2.4 mo
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once on day 1
7-day cycles
===Regimen variant #6, 1500 mg/m2, fixed-dose rate (FDR)===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Poplin et al. 2009 (ECOG E6201)	2003-2005 	Phase 3 (E-switch-ic)	1. Gemcitabine; standard	Might have longer OS (primary endpoint)Median OS: 6.2 vs 4.9 mo(HR 0.83, 95% CI 0.69-1.00)
Poplin et al. 2009 (ECOG E6201)	2003-2005 	Phase 3 (E-switch-ic)	2. GEMOX 	Did not meet primary endpoint of OS
====Chemotherapy====
*Gemcitabine (Gemzar) 1500 mg/m2 IV at fixed dose rate over 150 minutes once per day on days 1, 8, 15
28-day cycles
===References===
#Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Bramhall SR, Rosemurgy A, Brown PD, Bowry C, Buckels JA; Marimastat Pancreatic Cancer Study Group. Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol. 2001 Aug 1;19(15):3447-55. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Colucci G, Giuliani F, Gebbia V, Biglietto M, Rabitti P, Uomo G, Cigolari S, Testa A, Maiello E, Lopez M. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell'Italia Meridionale. Cancer. 2002 Feb 15;94(4):902-10. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Bramhall SR, Schulz J, Nemunaitis J, Brown PD, Baillet M, Buckels JA. A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br J Cancer. 2002 Jul 15;87(2):161-7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
#ECOG E2297: Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson AB 3rd. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol. 2002 Aug 1;20(15):3270-5. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#NCIC-CTG PA.1: Moore MJ, Hamm J, Dancey J, Eisenberg PD, Dagenais M, Fields A, Hagan K, Greenberg B, Colwell B, Zee B, Tu D, Ottaway J, Humphrey R, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Comparison of gemcitabine versus the matrix metalloproteinase inhibitor BAY 12-9566 in patients with advanced or metastatic adenocarcinoma of the pancreas: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2003 Sep 1;21(17):3296-302. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#CR003976: Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, Szawlowski A, Schoffski P, Post S, Verslype C, Neumann H, Safran H, Humblet Y, Perez Ruixo J, Ma Y, Von Hoff D. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol. 2004 Apr 15;22(8):1430-8. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00005648
#Rocha Lima CM, Green MR, Rotche R, Miller WH Jr, Jeffrey GM, Cisar LA, Morganti A, Orlando N, Gruia G, Miller LL. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol. 2004 Sep 15;22(18):3776-83. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A; GERCOR; GISCAD. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005 May 20;23(15):3509-16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#JMES: Oettle H, Richards D, Ramanathan RK, van Laethem JL, Peeters M, Fuchs M, Zimmermann A, John W, Von Hoff D, Arning M, Kindler HL. A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer. Ann Oncol. 2005 Oct;16(10):1639-45. Epub 2005 Aug 8. Erratum in: Ann Oncol. 2006 Mar;17(3):535. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00035035
#Reni M, Cordio S, Milandri C, Passoni P, Bonetto E, Oliani C, Luppi G, Nicoletti R, Galli L, Bordonaro R, Passardi A, Zerbi A, Balzano G, Aldrighetti L, Staudacher C, Villa E, Di Carlo V. Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial. Lancet Oncol. 2005 Jun;6(6):369-76. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#Stathopoulos GP, Syrigos K, Aravantinos G, Polyzos A, Papakotoulas P, Fountzilas G, Potamianou A, Ziras N, Boukovinas J, Varthalitis J, Androulakis N, Kotsakis A, Samonis G, Georgoulias V. A multicenter phase III trial comparing irinotecan-gemcitabine (IG) with gemcitabine (G) monotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer. Br J Cancer. 2006 Sep 4;95(5):587-92. Epub 2006 Aug 8. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC
#Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schönekäs H, Rost A, Neuhaus H, Haag C, Clemens M, Heinrich B, Vehling-Kaiser U, Fuchs M, Fleckenstein D, Gesierich W, Uthgenannt D, Einsele H, Holstege A, Hinke A, Schalhorn A, Wilkowski R. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol. 2006 Aug 20;24(24):3946-52. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#MSKCC 02-011: Abou-Alfa GK, Letourneau R, Harker G, Modiano M, Hurwitz H, Tchekmedyian NS, Feit K, Ackerman J, De Jager RL, Eckhardt SG, O'Reilly EM. Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. J Clin Oncol. 2006 Sep 20;24(27):4441-7. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00023972
#NCIC-CTG PA.3: Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. Epub 2007 Apr 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00026338
#SAKK 44/00-CECOG/PAN.1.3.001: Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W; Swiss Group for Clinical Cancer Research; Central European Cooperative Oncology Group. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol. 2007 Jun 1;25(16):2212-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00030732
##CBR/QoL analysis: Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Herrmann R; Central European Cooperative Oncology Group. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol. 2008 Aug 1;26(22):3695-701. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#A4061016: Spano JP, Chodkiewicz C, Maurel J, Wong R, Wasan H, Barone C, Létourneau R, Bajetta E, Pithavala Y, Bycott P, Trask P, Liau K, Ricart AD, Kim S, Rixe O. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study. Lancet. 2008 Jun 21;371(9630):2101-8. Epub 2008 May 29. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00219557
#ECOG E6201: Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, Alberts S, O'Dwyer P, Haller D, Catalano P, Cella D, Benson AB 3rd. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2009 Aug 10;27(23):3778-85. Epub 2009 Jul 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00058149
#CRUK GEM-CAP: Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009 Nov 20;27(33):5513-8. Epub 2009 Oct 26. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00032175
#GIP-1: Colucci G, Labianca R, Di Costanzo F, Gebbia V, Cartenì G, Massidda B, Dapretto E, Manzione L, Piazza E, Sannicolò M, Ciaparrone M, Cavanna L, Giuliani F, Maiello E, Testa A, Pederzoli P, Falconi M, Gallo C, Di Maio M, Perrone F; GOIM; GISCAD; GOIRC. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol. 2010 Apr 1;28(10):1645-51. Epub 2010 Mar 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00813696
#SWOG S0205: Philip PA, Benedetti J, Corless CL, Wong R, O'Reilly EM, Flynn PJ, Rowland KM, Atkins JN, Mirtsching BC, Rivkin SE, Khorana AA, Goldman B, Fenoglio-Preiser CM, Abbruzzese JL, Blanke CD. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol. 2010 Aug 1;28(22):3605-10. Epub 2010 Jul 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00075686
#CALGB 80303: Kindler HL, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H, Innocenti F, Mulcahy MF, O'Reilly E, Wozniak TF, Picus J, Bhargava P, Mayer RJ, Schilsky RL, Goldberg RM. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol. 2010 Aug 1;28(22):3617-22. Epub 2010 Jul 6. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT00088894
#FFCD 0301: Dahan L, Bonnetain F, Ychou M, Mitry E, Gasmi M, Raoul JL, Cattan S, Phelip JM, Hammel P, Chauffert B, Michel P, Legoux JL, Rougier P, Bedenne L, Seitz JF; Fédération Francophone de Cancérologie Digestive. Combination 5-fluorouracil, folinic acid and cisplatin (LV5FU2-CDDP) followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: final results of a randomised strategic phase III trial (FFCD 0301). Gut. 2010 Nov;59(11):1527-34. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT00303758
#A4061028: Kindler HL, Ioka T, Richel DJ, Bennouna J, Létourneau R, Okusaka T, Funakoshi A, Furuse J, Park YS, Ohkawa S, Springett GM, Wasan HS, Trask PC, Bycott P, Ricart AD, Kim S, Van Cutsem E. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study. Lancet Oncol. 2011 Mar;12(3):256-62. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00471146
##Subgroup analysis: Ioka T, Okusaka T, Ohkawa S, Boku N, Sawaki A, Fujii Y, Kamei Y, Takahashi S, Namazu K, Umeyama Y, Bycott P, Furuse J. Efficacy and safety of axitinib in combination with gemcitabine in advanced pancreatic cancer: subgroup analyses by region, including Japan, from the global randomized phase III trial. Jpn J Clin Oncol. 2015 May;45(5):439-48. Epub 2015 Feb 3. link to original article link to PMC article EuroPMC
#PRODIGE 4/ACCORD 11: Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00112658
##HRQoL analysis: Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Boige V, Bérille J, Conroy T. Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol. 2013 Jan 1;31(1):23-9. Epub 2012 Dec 3. link to original article EuroPMC
#BAYPAN: Gonçalves A, Gilabert M, François E, Dahan L, Perrier H, Lamy R, Re D, Largillier R, Gasmi M, Tchiknavorian X, Esterni B, Genre D, Moureau-Zabotto L, Giovannini M, Seitz JF, Delpero JR, Turrini O, Viens P, Raoul JL. BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer. Ann Oncol. 2012 Nov;23(11):2799-805. Epub 2012 Jul 5. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00541021
#GEST: Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013 May 1;31(13):1640-8. Epub 2013 Apr 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00498225
##Update: Okusaka T, Miyakawa H, Fujii H, Nakamori S, Satoh T, Hamamoto Y, Ito T, Maguchi H, Matsumoto S, Ueno H, Ioka T, Boku N, Egawa S, Hatori T, Furuse J, Mizumoto K, Ohkawa S, Yamaguchi T, Yamao K, Funakoshi A, Chen JS, Cheng AL, Sato A, Ohashi Y, Tanaka M; GEST group. Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer. J Cancer Res Clin Oncol. 2017 Jun;143(6):1053-1059. Epub 2017 Feb 16. link to original article link to PMC article EuroPMC
##HRQoL analysis: Hagiwara Y, Ohashi Y, Okusaka T, Ueno H, Ioka T, Boku N, Egawa S, Hatori T, Furuse J, Mizumoto K, Ohkawa S, Yamaguchi T, Yamao K, Funakoshi A, Cheng AL, Kihara K, Sato A, Tanaka M. Health-related quality of life in a randomised phase III study of gemcitabine plus S-1, S-1 alone and gemcitabine alone for locally advanced or metastatic pancreatic cancer: GEST study. ESMO Open. 2017;2(1):e000151. link to original article link to EuroPMC
#VANILLA: Rougier P, Riess H, Manges R, Karasek P, Humblet Y, Barone C, Santoro A, Assadourian S, Hatteville L, Philip PA. Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer. 2013 Aug;49(12):2633-42. Epub 2013 Apr 30. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00574275
#MPACT: Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. Epub 2013 Oct 16. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00844649
##Update: Goldstein D, El-Maraghi RH, Hammel P, Heinemann V, Kunzmann V, Sastre J, Scheithauer W, Siena S, Tabernero J, Teixeira L, Tortora G, Van Laethem JL, Young R, Penenberg DN, Lu B, Romano A, Von Hoff DD. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst. 2015 Jan 31;107(2). link to original article EuroPMC
##Subgroup analysis: Young R, Mainwaring P, Clingan P, Parnis FX, Asghari G, Beale P, Aly A, Botteman M, Romano A, Ferrara S, Margunato-Debay S, Harris M. nab-Paclitaxel plus gemcitabine in metastatic pancreatic adenocarcinoma: Australian subset analyses of the phase III MPACT trial. Asia Pac J Clin Oncol. 2018 Oct;14(5):e325-e331. Epub 2018 Jun 22. link to original article EuroPMC
#SMC 2008-07-065: Hong JY, Nam EM, Lee J, Park JO, Lee SC, Song SY, Choi SH, Heo JS, Park SH, Lim HY, Kang WK, Park YS. Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients. Cancer Chemother Pharmacol. 2014 Jan;73(1):125-30. Epub 2013 Oct 27. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00944463
#GAMMA: Fuchs CS, Azevedo S, Okusaka T, Van Laethem JL, Lipton LR, Riess H, Szczylik C, Moore MJ, Peeters M, Bodoky G, Ikeda M, Melichar B, Nemecek R, Ohkawa S, Świeboda-Sadlej A, Tjulandin SA, Van Cutsem E, Loberg R, Haddad V, Gansert JL, Bach BA, Carrato A. A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. Ann Oncol. 2015 May;26(5):921-7. Epub 2015 Jan 21. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01231347
#AB07012: Deplanque G, Demarchi M, Hebbar M, Flynn P, Melichar B, Atkins J, Nowara E, Moyé L, Piquemal D, Ritter D, Dubreuil P, Mansfield CD, Acin Y, Moussy A, Hermine O, Hammel P. A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer. Ann Oncol. 2015 Jun;26(6):1194-200. Epub 2015 Apr 9. link to original article link to PMC article EuroPMC NCT00789633
#ONTRAC: O'Neil BH, Scott AJ, Ma WW, Cohen SJ, Leichman L, Aisner DL, Menter AR, Tejani MA, Cho JK, Granfortuna J, Coveler AL, Olowokure OO, Baranda JC, Cusnir M, Philip P, Boles J, Nazemzadeh R, Rarick M, Cohen DJ, Radford J, Fehrenbacher L, Bajaj R, Bathini V, Fanta P, Berlin J, McRee AJ, Maguire R, Wilhelm F, Maniar M, Jimeno A, Gomes CL, Messersmith WA. A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer. Ann Oncol. 2015 Sep;26(9):1923-9. Epub 2015 Jun 19. Erratum in: Ann Oncol. 2015 Dec;26(12):2505. Leichman, L [added]. Ann Oncol. 2016 Jun;27(6):1180. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT01360853
#UCCRC-8418: Catenacci DV, Junttila MR, Karrison T, Bahary N, Horiba MN, Nattam SR, Marsh R, Wallace J, Kozloff M, Rajdev L, Cohen D, Wade J, Sleckman B, Lenz HJ, Stiff P, Kumar P, Xu P, Henderson L, Takebe N, Salgia R, Wang X, Stadler WM, de Sauvage FJ, Kindler HL. Randomized phase Ib/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer. J Clin Oncol. 2015 Dec 20;33(36):4284-92. Epub 2015 Nov 2. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT01064622
#Lee HS, Chung MJ, Park JY, Bang S, Park SW, Kim HG, Noh MH, Lee SH, Kim YT, Kim HJ, Kim CD, Lee DK, Cho KB, Cho CM, Moon JH, Kim DU, Kang DH, Cheon YK, Choi HS, Kim TH, Kim JK, Moon J, Shin HJ, Song SY; Korean Society of Gastrointestinal Cancer. A randomized, multicenter, phase III study of gemcitabine combined with capecitabine versus gemcitabine alone as first-line chemotherapy for advanced pancreatic cancer in South Korea. Medicine (Baltimore). 2017 Jan;96(1):e5702. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
#ViP: Middleton G, Palmer DH, Greenhalf W, Ghaneh P, Jackson R, Cox T, Evans A, Shaw VE, Wadsley J, Valle JW, Propper D, Wasan H, Falk S, Cunningham D, Coxon F, Ross P, Madhusudan S, Wadd N, Corrie P, Hickish T, Costello E, Campbell F, Rawcliffe C, Neoptolemos JP. Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial. Lancet Oncol. 2017 Apr;18(4):486-499. Epub 2017 Mar 2. link to original article dosing details in abstract have been reviewed by our editors EuroPMC ISRCTN96397434
#NOTABLE: Qin S, Li J, Bai Y, Wang Z, Chen Z, Xu R, Xu J, Zhang H, Chen J, Yuan Y, Liu T, Yang L, Zhong H, Chen D, Shen L, Hao C, Fu D, Cheng Y, Yang J, Wang Q, Qin B, Pan H, Zhang J, Bai X, Zheng Q. Nimotuzumab Plus Gemcitabine for K-Ras Wild-Type Locally Advanced or Metastatic Pancreatic Cancer. J Clin Oncol. 2023 Nov 20;41(33):5163-5173. Epub 2023 Aug 30. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02395016
==GemOx==
GemOx: Gemcitabine & Oxaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Louvet et al. 2005 	2001-2003 	Phase 3 (E-esc)	Gemcitabine 	Seems to have longer PFS (secondary endpoint)Median PFS: 5.8 vs 3.7 mo(HR 0.78, 95% CI 0.59-0.99)
Poplin et al. 2009 (ECOG E6201)	2003-2005 	Phase 3 (E-esc)	1. Gemcitabine; standard 	Did not meet primary endpoint of OS
Poplin et al. 2009 (ECOG E6201)	2003-2005 	Phase 3 (E-esc)	2. Gemcitabine; fixed dose rate	Did not meet primary endpoint of OS
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 100 minutes once on day 1
*Oxaliplatin (Eloxatin) 100 mg/m2 IV over 2 hours once on day 2
14-day cycles
===References===
#Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A; GERCOR; GISCAD. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005 May 20;23(15):3509-16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#ECOG E6201: Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, Alberts S, O'Dwyer P, Haller D, Catalano P, Cella D, Benson AB 3rd. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2009 Aug 10;27(23):3778-85. Epub 2009 Jul 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00058149
==Gemcitabine & nab-Paclitaxel==
NG: Nab-Paclitaxel & Gemcitabine
AG: Abraxane (nab-Paclitaxel) & Gemcitabine
===Regimen variant #1, with 8-week lead-in===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Von Hoff et al. 2013 (MPACT)	2009-2012 	Phase 3 (E-RT-esc)	Gemcitabine	Longer OS1 (primary endpoint)Median OS: 8.7 vs 6.6 mo(HR 0.72, 95% CI 0.62-0.83)
1Reported efficacy is based on the 2015 update.
====Chemotherapy====
*Gemcitabine (Gemzar) as follows, given second:
**Cycle 1: 1000 mg/m2 IV once per day on days 1, 8, 15, 29, 36, 43
**Cycle 2 onwards: 1000 mg/m2 IV once per day on days 1, 8, 15
*Paclitaxel, nanoparticle albumin-bound (Abraxane) as follows, given first:
**Cycle 1: 125 mg/m2 IV over 30 to 40 minutes once per day on days 1, 8, 15, 29, 36, 43
**Cycle 2 onwards: 125 mg/m2 IV over 30 to 40 minutes once per day on days 1, 8, 15
8-week course, then 28-day cycles
===Regimen variant #2, no lead-in===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Von Hoff et al. 2011 (CA040) 	2006 to not reported 	Phase 1/2 	 	
Tempero et al. 2021 (RESOLVE) 	2015 to not reported 	Phase 3 (C)	Ibrutinib, Gemcitabine, nab-Paclitaxel 	Did not meet primary endpoint of OSMedian OS: 10.8 vs 9.7 mo
Van Cutsem et al. 2020 (HALO 109-301)	2016-2018 	Phase 3 (C)	AG & PEGPH20 	Did not meet primary endpoint of OSMedian OS: 11.5 vs 11.2 mo(HR 1.00, 95% CI 0.79-1.25)
Bekaii-Saab et al. 2023 (CanStem111P)	2017-01-30 to 2019-02-20	Phase 3 (C)	Gemcitabine, nab-Paclitaxel, Napabucasin	Did not meet primary endpoint of OSMedian OS: 11.7 vs 11.4 mo(HR 0.93, 95% CI 0.81-1.08)
Wainberg et al. 2023 (NAPOLI 3) 	2020-02-19 to 2021-08-17	Phase 3 (C)	NALIRIFOX 	Seems to have shorter OSMedian OS: 9.2 vs 11.1 mo(HR 1.20, 95% CI 1.01-1.43)
Note: The abstract and body of Von Hoff et al. 2011 contradicted each other about which drug is given first in this regimen. The dosing here is from HALO 109-301. To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Biomarker eligibility criteria====
*HALO 109-301: Hyaluronan-high
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
*Paclitaxel, nanoparticle albumin-bound (Abraxane) 125 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
===References===
#CA040: Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011 Dec 1;29(34):4548-54. Epub 2011 Oct 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00398086
#MPACT: Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. Epub 2013 Oct 16. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00844649
##Update: Goldstein D, El-Maraghi RH, Hammel P, Heinemann V, Kunzmann V, Sastre J, Scheithauer W, Siena S, Tabernero J, Teixeira L, Tortora G, Van Laethem JL, Young R, Penenberg DN, Lu B, Romano A, Von Hoff DD. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst. 2015 Jan 31;107(2). link to original article EuroPMC
##Subgroup analysis: Young R, Mainwaring P, Clingan P, Parnis FX, Asghari G, Beale P, Aly A, Botteman M, Romano A, Ferrara S, Margunato-Debay S, Harris M. nab-Paclitaxel plus gemcitabine in metastatic pancreatic adenocarcinoma: Australian subset analyses of the phase III MPACT trial. Asia Pac J Clin Oncol. 2018 Oct;14(5):e325-e331. Epub 2018 Jun 22. link to original article EuroPMC
#HALO 109-301: Van Cutsem E, Tempero MA, Sigal D, Oh DY, Fazio N, Macarulla T, Hitre E, Hammel P, Hendifar AE, Bates SE, Li CP, Hingorani SR, de la Fouchardiere C, Kasi A, Heinemann V, Maraveyas A, Bahary N, Layos L, Sahai V, Zheng L, Lacy J, Park JO, Portales F, Oberstein P, Wu W, Chondros D, Bullock AJ; HALO 109-301 Investigators. Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma. J Clin Oncol. 2020 Sep 20;38(27):3185-3194. Epub 2020 Jul 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02715804
#RESOLVE: Tempero M, Oh DY, Tabernero J, Reni M, Van Cutsem E, Hendifar A, Waldschmidt DT, Starling N, Bachet JB, Chang HM, Maurel J, Garcia-Carbonero R, Lonardi S, Coussens LM, Fong L, Tsao LC, Cole G Jr, James D, Macarulla T. Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study. Ann Oncol. 2021 May;32(5):600-608. Epub 2021 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02436668
#CanStem111P: Bekaii-Saab T, Okusaka T, Goldstein D, Oh DY, Ueno M, Ioka T, Fang W, Anderson EC, Noel MS, Reni M, Choi HJ, Goldberg JS, Oh SC, Li CP, Tabernero J, Li J, Foos E, Oh C, Van Cutsem E. Napabucasin plus nab-paclitaxel with gemcitabine versus nab-paclitaxel with gemcitabine in previously untreated metastatic pancreatic adenocarcinoma: an adaptive multicentre, randomised, open-label, phase 3, superiority trial. EClinicalMedicine. 2023 Mar 16;58:101897. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02993731
#NAPOLI 3: Wainberg ZA, Melisi D, Macarulla T, Pazo Cid R, Chandana SR, De La Fouchardière C, Dean A, Kiss I, Lee WJ, Goetze TO, Van Cutsem E, Paulson AS, Bekaii-Saab T, Pant S, Hubner RA, Xiao Z, Chen H, Benzaghou F, O'Reilly EM. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023 Oct 7;402(10409):1272-1281. Epub 2023 Sep 11. link to original article EuroPMC NCT04083235
#GRASPANC 2018-01: NCT03665441
==Gemcitabine & Nimotuzumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Qin et al. 2023 (NOTABLE)	2015-04 to 2021-03 	Phase 3 (E-esc)	Gemcitabine	Seems to have longer OS (primary endpoint)Median OS: 10.9 vs 8.5 mo(RMST ratio 0.62, 95% CI 0.40-0.97)
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15, 29, 36, 43
====Targeted therapy====
*Nimotuzumab (Theraloc) 400 mg IV once per day on days 1, 8, 15, 22, 29, 36, 43
8-week cycles
===References===
#NOTABLE: Qin S, Li J, Bai Y, Wang Z, Chen Z, Xu R, Xu J, Zhang H, Chen J, Yuan Y, Liu T, Yang L, Zhong H, Chen D, Shen L, Hao C, Fu D, Cheng Y, Yang J, Wang Q, Qin B, Pan H, Zhang J, Bai X, Zheng Q. Nimotuzumab Plus Gemcitabine for K-Ras Wild-Type Locally Advanced or Metastatic Pancreatic Cancer. J Clin Oncol. 2023 Nov 20;41(33):5163-5173. Epub 2023 Aug 30. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02395016
==GTX==
GTX: Gemcitabine, Taxotere (Docetaxel), Xeloda (Capecitabine)
===Regimen===
Study 	Dates of enrollment	Evidence
Fine et al. 2007	2001-01 to 2003-01 	Retrospective
Note: De Jesus-Acosta et al. 2012 listed the capecitabine dose as "750 mg/m2/day orally divided into two doses," but this is believed to be a typographical error since the original reference that it cites, Fine et al. 2007, used capecitabine at 750 mg/m2 PO twice per day. The 2009 ASCO abstract by Fine also listed this 750 mg/m2 PO twice per day (1500 mg/m2/day) dose.
====Chemotherapy====
*Gemcitabine (Gemzar) 750 mg/m2 IV over 75 minutes once per day on days 4 & 11
*Docetaxel (Taxotere) 30 mg/m2 IV once per day on days 4 & 11
*Capecitabine (Xeloda) 750 mg/m2 PO twice per day on days 1 to 14
21-day cycles
===References===
#Retrospective: Fine RL, Fogelman DR, Schreibman SM, Desai M, Sherman W, Strauss J, Guba S, Andrade R, Chabot J. The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis. Cancer Chemother Pharmacol. 2008 Jan;61(1):167-75. Epub 2007 Apr 18. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#Abstract: R. L. Fine, G. Moorer, W. Sherman, K. Chu, M. Maurer, J. Chabot, I. Postolov, J. Prowda, S. Schreibman, J. Levitz. Phase II trial of GTX chemotherapy in metastatic pancreatic cancer. 2009 ASCO Annual Meeting abstract 4623. link to abstract content property of HemOnc.org
#Retrospective: De Jesus-Acosta A, Oliver GR, Blackford A, Kinsman K, Flores EI, Wilfong LS, Zheng L, Donehower RC, Cosgrove D, Laheru D, Le DT, Chung K, Diaz LA Jr. A multicenter analysis of GTX chemotherapy in patients with locally advanced and metastatic pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2012 Feb;69(2):415-24. Epub 2011 Jul 29. link to original article dosing details in manuscript have been reviewed by our editors--with error as noted above link to PMC article EuroPMC
==NALIRIFOX==
NALIRIFOX: NAnoLIposomal IRInotecan, Fluorouracil, OXaliplatin
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wainberg et al. 2023 (NAPOLI 3)	2020-02-19 to 2021-08-17	Phase 3 (E-RT-esc)	Gemcitabine & nab-Paclitaxel	Seems to have longer OS (primary endpoint)Median OS: 11.1 vs 9.2 mo(HR 0.83, 95% CI 0.70-0.99)
====Chemotherapy====
*Irinotecan liposome (Onivyde) 50 mg/m2 IV once on day 1
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1, given last
*Oxaliplatin (Eloxatin) 60 mg/m2 IV once on day 1
14-day cycles
===References===
#NAPOLI 3: Wainberg ZA, Melisi D, Macarulla T, Pazo Cid R, Chandana SR, De La Fouchardière C, Dean A, Kiss I, Lee WJ, Goetze TO, Van Cutsem E, Paulson AS, Bekaii-Saab T, Pant S, Hubner RA, Xiao Z, Chen H, Benzaghou F, O'Reilly EM. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023 Oct 7;402(10409):1272-1281. Epub 2023 Sep 11. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT04083235
==S-1 monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ueno et al. 2013 (GEST)	2007-2009 	Phase 3 (E-switch-ic)	1. Gemcitabine 	Non-inferior OS (primary endpoint)Median OS: 9.7 vs 8.8 mo(HR 0.96, 97.5% CI 0.78-1.18)
Ueno et al. 2013 (GEST)	2007-2009 	Phase 3 (E-switch-ic)	2. Gemcitabine & S-1	Not reported
====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 up to 1.50 m2: 50 mg PO twice per day on days 1 to 28
**1.50 m2 or more: 60 mg PO twice per day on days 1 to 28
42-day cycles
===References===
#GEST: Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013 May 1;31(13):1640-8. Epub 2013 Apr 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00498225
##Update: Okusaka T, Miyakawa H, Fujii H, Nakamori S, Satoh T, Hamamoto Y, Ito T, Maguchi H, Matsumoto S, Ueno H, Ioka T, Boku N, Egawa S, Hatori T, Furuse J, Mizumoto K, Ohkawa S, Yamaguchi T, Yamao K, Funakoshi A, Chen JS, Cheng AL, Sato A, Ohashi Y, Tanaka M; GEST group. Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer. J Cancer Res Clin Oncol. 2017 Jun;143(6):1053-1059. Epub 2017 Feb 16. link to original article link to PMC article EuroPMC
##HRQoL analysis: Hagiwara Y, Ohashi Y, Okusaka T, Ueno H, Ioka T, Boku N, Egawa S, Hatori T, Furuse J, Mizumoto K, Ohkawa S, Yamaguchi T, Yamao K, Funakoshi A, Cheng AL, Kihara K, Sato A, Tanaka M. Health-related quality of life in a randomised phase III study of gemcitabine plus S-1, S-1 alone and gemcitabine alone for locally advanced or metastatic pancreatic cancer: GEST study. ESMO Open. 2017;2(1):e000151. link to original article link to EuroPMC
=Metastatic disease, gemcitabine-refractory=
==Capecitabine & Erlotinib==
===Regimen===
Study 	Dates of enrollment	Evidence
Kulke et al. 2007	Not reported 	Phase 2
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 (rounded to the nearest 150 mg tablet) PO twice per day on days 1 to 14
====Targeted therapy====
*Erlotinib (Tarceva) 150 mg PO on days 1 to 21
21-day cycles
===References===
#Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, Enzinger PC, Kwak EL, Muzikansky A, Lawrence C, Fuchs CS. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol. 2007 Oct 20;25(30):4787-92. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CapeOx==
CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda (Capecitabine), OXaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence
Xiong et al. 2008	2004-2005 	Phase 2
====Chemotherapy====
*Capecitabine (Xeloda) by the following age- and performance-based criteria:
**Younger than 65 years old AND ECOG performance status less than 2: 1000 mg/m2 PO twice per day on days 1 to 14
**65 years old or older OR ECOG performance status 2 or more: 750 mg/m2 PO twice per day on days 1 to 14
*Oxaliplatin (Eloxatin) by the following age- and performance-based criteria:
**Younger than 65 years old AND ECOG performance status less than 2: 130 mg/m2 IV over 2 hours once on day 1
**65 years old or older OR ECOG performance status 2 or more: 110 mg/m2 IV over 2 hours once on day 1
21-day cycles
===References===
#Xiong HQ, Varadhachary GR, Blais JC, Hess KR, Abbruzzese JL, Wolff RA. Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer. 2008 Oct 15;113(8):2046-52. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==FULV==
FULV: 5-FU & LeucoVorin
FF: Fluorouracil & Folinic acid (Leucovorin)
===Regimen variant #1, 2000/200, q2wk===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Cui et al. 2024 (PAN-HEROIC-1)	2018-01-25 to 2021-05-26	Phase 3 (C)	FULV & nanoliposomal Irinotecan	Shorter OSMedian OS: 5 vs 7.4 mo(HR 1.59, 95% CI 1.19-2.08)
====Chemotherapy====
*Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 46 hours, started on day 1, given second
*Leucovorin (Folinic acid) 200 mg/m2 IV over 30 minutes once on day 1, given first
14-day cycles
===Regimen variant #2, 2000/200, q6 wk===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Oettle et al. 2014 (CONKO-003 part 2)	2004-2007 	Phase 3 (C)	OFF 	Shorter OSMedian OS: 3.3 vs 5.9 mo(HR 1.52, 95% CI 1.10-2.08)
Wang-Gillam et al. 2015 (NAPOLI-1) 	2012-01-11 to 2013-09-11	Phase 3 (C)	1. FULV & nanoliposomal Irinotecan	Seems to have shorter OS1
Wang-Gillam et al. 2015 (NAPOLI-1) 	2012-01-11 to 2013-09-11	Phase 3 (C)	2. Irinotecan, nanoliposomal 	Not reported
1Reported efficacy is based on the 2019 update.
====Chemotherapy====
*Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, given second (total dose per cycle: 8000 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV once per day on days 1, 8, 15, 22, given first
42-day cycles
===Regimen variant #3, 2800/400===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Gill et al. 2016 (PANCREOX)	2010-2012 	Phase 3 (C)	mFOLFOX6 	Did not meet primary endpoint of PFSMedian PFS: 2.9 vs 3.1 mo(HR 1.00, 95% CI 0.65-1.52)
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given second (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given first
14-day cycles
===References===
#CONKO-003 part 2: Oettle H, Riess H, Stieler JM, Heil G, Schwaner I, Seraphin J, Görner M, Mölle M, Greten TF, Lakner V, Bischoff S, Sinn M, Dörken B, Pelzer U. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014 Aug 10;32(23):2423-9. Epub 2014 Jun 30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00786058
#NAPOLI-1: Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT; NAPOLI-1 Study Group. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545-57. Epub 2015 Nov 29. Erratum in: Lancet. 2016 Feb 6;387(10018):536. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01494506
##Q-TWiST analysis: Pelzer U, Blanc JF, Melisi D, Cubillo A, Von Hoff DD, Wang-Gillam A, Chen LT, Siveke JT, Wan Y, Solem CT, Botteman MF, Yang Y, de Jong FA, Hubner RA. Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis. Br J Cancer. 2017 May 9;116(10):1247-1253. Epub 2017 Mar 28. link to original article link to PMC article EuroPMC
##HRQoL analysis: Hubner RA, Cubillo A, Blanc JF, Melisi D, Von Hoff DD, Wang-Gillam A, Chen LT, Becker C, Mamlouk K, Belanger B, Yang Y, de Jong FA, Siveke JT. Quality of life in metastatic pancreatic cancer patients receiving liposomal irinotecan plus 5-fluorouracil and leucovorin. Eur J Cancer. 2019 Jan;106:24-33. Epub 2018 Nov 17. link to original article EuroPMC
##Update: Wang-Gillam A, Hubner RA, Siveke JT, Von Hoff DD, Belanger B, de Jong FA, Mirakhur B, Chen LT. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: final overall survival analysis and characteristics of long-term survivors. Eur J Cancer. 2019 Feb 108;78-87. Epub 2019 Jan 14. link to original article EuroPMC
##Subgroup analysis: Bang YJ, Li CP, Lee KH, Chiu CF, Park JO, Shan YS, Kim JS, Chen JS, Shim HJ, Rau KM, Choi HJ, Oh DY, Belanger B, Chen LT. Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study. Cancer Sci. 2020 Feb;111(2):513-527. Epub 2019 Dec 20. link to original article link to PMC article EuroPMC
#PANCREOX: Gill S, Ko YJ, Cripps C, Beaudoin A, Dhesy-Thind S, Zulfiqar M, Zalewski P, Do T, Cano P, Lam WYH, Dowden S, Grassin H, Stewart J, Moore M. PANCREOX: a randomized phase III study of fluorouracil/leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy. J Clin Oncol. 2016 Nov 10;34(32):3914-3920. Epub 2016 Sep 30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01121848
#PAN-HEROIC-1: Cui J, Qin S, Zhou Y, Zhang S, Sun X, Zhang M, Cui J, Fang W, Gu K, Li Z, Wang J, Chen X, Yao J, Zhou J, Wang G, Bai Y, Xiao J, Qiu W, Wang B, Xia T, Wang C, Kong L, Yin J, Zhang T, Shen X, Fu D, Gao C, Wang H, Wang Q, Wang L. Irinotecan hydrochloride liposome HR070803 in combination with 5-fluorouracil and leucovorin in locally advanced or metastatic pancreatic ductal adenocarcinoma following prior gemcitabine-based therapy (PAN-HEROIC-1): a phase 3 trial. Signal Transduct Target Ther. 2024 Sep 19;9(1):248. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT05074589
==FULV & nanoliposomal Irinotecan==
FULV & nanoliposomal Irinotecan: 5-FU, LeucoVorin, nanoliposomal Irinotecan
===Regimen variant #1, 2000/200/56.5===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Cui et al. 2024 (PAN-HEROIC-1)	2018-01-25 to 2021-05-26	Phase 3 (E-esc)	FULV 	Longer OS (primary endpoint)Median OS: 7.4 vs 5 mo(HR 0.63, 95% CI 0.48-0.84)
Note: The liposomal irinotecan used in this trial was an experimental agent, HR-070803 - not Onivyde.
====Chemotherapy====
*Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 46 hours, started on day 1, given third
*Leucovorin (Folinic acid) 200 mg/m2 IV over 30 minutes once on day 1, given second
*Irinotecan liposome (Onivyde) 56.5 mg/m2 (irinotecan free base) IV over 90 minutes once on day 1, given first
14-day cycles
===Regimen variant #2, 2400/400/70===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wang-Gillam et al. 2015 (NAPOLI-1)	2012-01-11 to 2013-09-11	Phase 3 (E-RT-esc)	1. FULV 	Seems to have longer OS1 (primary endpoint)Median OS: 4.9 vs 4.2 mo(HR 0.75, 95% CI 0.57-0.99)
Wang-Gillam et al. 2015 (NAPOLI-1)	2012-01-11 to 2013-09-11	Phase 3 (E-RT-esc)	2. Irinotecan, nanoliposomal	Not reported
1Reported efficacy is based on the 2019 update.
====Chemotherapy====
*Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1, given third
*Leucovorin (Folinic acid) 400 mg/m2 IV over 30 minutes once on day 1, given second
*Irinotecan liposome (Onivyde) 70 mg/m2 (irinotecan free base) IV over 90 minutes once on day 1, given first
**Per Wang-Gillam et al. 2015 (NAPOLI-1), 70 mg/m2 irinotecan free base is equivalent to 80 mg/m2 nanoliposomal irinotecan. According to the trial's ClinicalTrials.gov page: "The published dose of ONIVYDE was expressed as the irinotecan hydrochloride trihydrate until October 2015. It is now expressed as the irinotecan free base. Converting a dose based on irinotecan hydrochloride trihydrate to a dose based on irinotecan free base is accomplished by substituting the Molecular Weight of irinotecan hydrochloride trihydrate (677.19 g/mole) with the Molecular Weight of irinotecan free base (586.68 g/mole), which results in a conversion factor of 0.866. 80 mg/m2 dose of irinotecan hydrochloride trihydrate is equivalent to 70 mg/m2 of irinotecan free base."
14-day cycles
===References===
#NAPOLI-1: Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT; NAPOLI-1 Study Group. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545-57. Epub 2015 Nov 29. Erratum in: Lancet. 2016 Feb 6;387(10018):536. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01494506
##Q-TWiST analysis: Pelzer U, Blanc JF, Melisi D, Cubillo A, Von Hoff DD, Wang-Gillam A, Chen LT, Siveke JT, Wan Y, Solem CT, Botteman MF, Yang Y, de Jong FA, Hubner RA. Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis. Br J Cancer. 2017 May 9;116(10):1247-1253. Epub 2017 Mar 28. link to original article link to PMC article EuroPMC
##HRQoL analysis: Hubner RA, Cubillo A, Blanc JF, Melisi D, Von Hoff DD, Wang-Gillam A, Chen LT, Becker C, Mamlouk K, Belanger B, Yang Y, de Jong FA, Siveke JT. Quality of life in metastatic pancreatic cancer patients receiving liposomal irinotecan plus 5-fluorouracil and leucovorin. Eur J Cancer. 2019 Jan;106:24-33. Epub 2018 Nov 17. link to original article EuroPMC
##Update: Wang-Gillam A, Hubner RA, Siveke JT, Von Hoff DD, Belanger B, de Jong FA, Mirakhur B, Chen LT. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: final overall survival analysis and characteristics of long-term survivors. Eur J Cancer. 2019 Feb 108;78-87. Epub 2019 Jan 14. link to original article EuroPMC
##Subgroup analysis: Bang YJ, Li CP, Lee KH, Chiu CF, Park JO, Shan YS, Kim JS, Chen JS, Shim HJ, Rau KM, Choi HJ, Oh DY, Belanger B, Chen LT. Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study. Cancer Sci. 2020 Feb;111(2):513-527. Epub 2019 Dec 20. link to original article link to PMC article EuroPMC
#PAN-HEROIC-1: Cui J, Qin S, Zhou Y, Zhang S, Sun X, Zhang M, Cui J, Fang W, Gu K, Li Z, Wang J, Chen X, Yao J, Zhou J, Wang G, Bai Y, Xiao J, Qiu W, Wang B, Xia T, Wang C, Kong L, Yin J, Zhang T, Shen X, Fu D, Gao C, Wang H, Wang Q, Wang L. Irinotecan hydrochloride liposome HR070803 in combination with 5-fluorouracil and leucovorin in locally advanced or metastatic pancreatic ductal adenocarcinoma following prior gemcitabine-based therapy (PAN-HEROIC-1): a phase 3 trial. Signal Transduct Target Ther. 2024 Sep 19;9(1):248. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT05074589
==FOLFIRI==
FOLFIRI: FOLinic acid (Leucovorin), Fluorouracil, IRInotecan
===Regimen variant #1===
Study 	Dates of enrollment	Evidence
Zaniboni et al. 2012 (SLAP)	2010-2011 	Phase 2
====Chemotherapy====
*Leucovorin (Folinic acid) 200 mg/m2 IV once per day on days 1 & 2
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1 & 2, then 600 mg/m2 IV continuous infusion over 22 hours after each bolus (total dose per cycle: 2000 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
14-day cycles
===Regimen variant #2, modified FOLFIRI.3===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Yoo et al. 2009 (AMC P 01)	2007-2008 	Randomized Phase 2 (E-switch-ic)	mFOLFOX 	Did not meet primary endpoint of OS6
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1
*Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 46 hours, started on day 1
*Irinotecan (Camptosar) 70 mg/m2 IV once per day on days 1 & 3, with day 3 dose given at end of 5-FU infusion
14-day cycles
===References===
#AMC P 01: Yoo C, Hwang JY, Kim JE, Kim TW, Lee JS, Park DH, Lee SS, Seo DW, Lee SK, Kim MH, Han DJ, Kim SC, Lee JL. A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer. 2009 Nov 17;101(10):1658-63. Epub 2009 Oct 13. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00786006
#SLAP: Zaniboni A, Aitini E, Barni S, Ferrari D, Cascinu S, Catalano V, Valmadre G, Ferrara D, Veltri E, Codignola C, Labianca R. FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multicenter phase II study. Cancer Chemother Pharmacol. 2012 Jun;69(6):1641-5. Epub 2012 May 11. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT01543412
==mFOLFIRINOX==
mFOLFIRINOX: modified FOLinic acid (Leucovorin), Fluorouracil, IRINotecan, OXaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Go et al. 2021 (MPACA-3)	2017-2019 	Phase 3 (E-esc)	S-1 	Longer OS (primary endpoint)Median OS: 9.2 vs 4.9 mo(aHR 0.40, 95% CI 0.20-0.70)
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 1000 mg/m2 IV continuous infusion over 24 hours, started on day 1
*Irinotecan (Camptosar) 135 mg/m2 IV once on day 1
*Oxaliplatin (Eloxatin) 65 mg/m2 IV once on day 1
14-day cycles
===References===
#MPACA-3: Go SI, Lee SC, Bae WK, Zang DY, Lee HW, Jang JS, Ji JH, Kim JH, Park S, Sym SJ, Yang Y, Jeon SY, Hwang IG, Oh SY, Kang JH. Modified FOLFIRINOX versus S-1 as second-line chemotherapy in gemcitabine-failed metastatic pancreatic cancer patients: A randomised controlled trial (MPACA-3). Eur J Cancer. 2021 Nov;157:21-30. Epub 2021 Aug 28. link to original article EuroPMC KCT0003534
==FOLFOX==
FOLFOX: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Yoo et al. 2009 (AMC P 01)	2007-2008 	Randomized Phase 2 (E-switch-ic)	mFOLFIRI.3	Did not meet primary endpoint of OS6
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 2000 mg/m2 IV once per day on days 1 & 2
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycles
===References===
#AMC P 01: Yoo C, Hwang JY, Kim JE, Kim TW, Lee JS, Park DH, Lee SS, Seo DW, Lee SK, Kim MH, Han DJ, Kim SC, Lee JL. A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer. 2009 Nov 17;101(10):1658-63. Epub 2009 Oct 13. link to original article dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT00786006
==mFOLFOX6==
mFOLFOX6: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hecht et al. 2021 (SEQUOIA)	2017-2019 	Phase 3 (C)	mFOLFOX6 & Pegilodecakin	Did not meet primary endpoint of OSMedian OS: 6.3 vs 5.8 mo(HR 0.96, 95% CI 0.79-1.16)
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, given third, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV over 120 minutes once on day 1, given first
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycle for up to 12 cycles
===References===
#SEQUOIA: Hecht JR, Lonardi S, Bendell J, Sim HW, Macarulla T, Lopez CD, Van Cutsem E, Muñoz Martin AJ, Park JO, Greil R, Wang H, Hozak RR, Gueorguieva I, Lin Y, Rao S, Ryoo BY. Randomized Phase III Study of FOLFOX Alone or With Pegilodecakin as Second-Line Therapy in Patients With Metastatic Pancreatic Cancer That Progressed After Gemcitabine (SEQUOIA). J Clin Oncol. 2021 Apr 1;39(10):1108-1118. Epub 2021 Feb 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02923921
==Irinotecan liposomal monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Ko et al. 2013 (PEP0208)	2009-2010 	Phase 2
====Chemotherapy====
*Irinotecan liposome (Onivyde) 120 mg/m2 IV once on day 1
21-day cycles
===References===
#PEP0208: Ko AH, Tempero MA, Shan YS, Su WC, Lin YL, Dito E, Ong A, Wang YW, Yeh CG, Chen LT. A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer. Br J Cancer. 2013 Aug 20;109(4):920-5. Epub 2013 Jul 23. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT00813163
==OLF==
OLF: Oxaliplatin, Leucovorin, Fluorouracil
OFF: Oxaliplatin, Fluorouracil, Folinic acid (Leucovorin) 
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Pelzer et al. 2011 (CONKO-003) 	2002-12 to 2003-12 	Phase 3 (E-esc)	Best supportive care	Longer OS (primary endpoint)Median OS: 9.09 vs 7.9 mo(HR 0.50, 95% CI 0.27-0.95)
Oettle et al. 2014 (CONKO-003 part 2)	2004-2007 	Phase 3 (E-esc)	FULV 	Longer OS (primary endpoint)Median OS: 5.9 vs 3.3 mo(HR 0.66, 95% CI 0.48-0.91)
Note: The treatment section of Pelzer et al. 2011 incorrectly lists the oxaliplatin dose as "0.85 g/m2," or 850 mg/m2. Note also that the trial was modified and reinitiated and is labeled as "Part 2" to explain this.
====Chemotherapy====
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 to 4 hours once per day on days 8 & 22, given first
*Leucovorin (Folinic acid) 200 mg/m2 IV bolus once per day on days 1, 8, 15, 22, given second
*Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, given third (total dose per cycle: 8000 mg/m2)
42-day cycles
===References===
#CONKO-003: Pelzer U, Schwaner I, Stieler J, Adler M, Seraphin J, Dörken B, Riess H, Oettle H. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer. 2011 Jul;47(11):1676-81. Epub 2011 May 10. link to original article dosing details in manuscript have been reviewed by our editors--with error as noted above EuroPMC NCT00786058
#CONKO-003 part 2: Oettle H, Riess H, Stieler JM, Heil G, Schwaner I, Seraphin J, Görner M, Mölle M, Greten TF, Lakner V, Bischoff S, Sinn M, Dörken B, Pelzer U. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014 Aug 10;32(23):2423-9. Epub 2014 Jun 30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00786058
==nab-Paclitaxel monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Hosein et al. 2013	2008-07 to 2009-04 	Phase 2
====Chemotherapy====
*Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
===References===
#Hosein PJ, de Lima Lopes G Jr, Pastorini VH, Gomez C, Macintyre J, Zayas G, Reis I, Montero AJ, Merchan JR, Rocha Lima CM. A phase II trial of nab-paclitaxel as second-line therapy in patients with advanced pancreatic cancer. Am J Clin Oncol. 2013 Apr;36(2):151-6. Epub 2012 Feb 2. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==S-1 monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ioka et al. 2018 (GRAPE)	2013-2015 	Phase 3 (C)	TAS-118 	Did not meet primary endpoint of OSMedian OS: 7.9 vs 7.6 mo(HR 1.02, 95% CI 0.86-1.22)
Go et al. 2021 (MPACA-3)	2017-2019 	Phase 3 (C)	mFOLFIRINOX	Shorter OS (primary endpoint)Median OS: 4.9 vs 9.2 mo(aHR 2.50, 95% CI 1.43-5.00)
====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 up to 1.50 m2: 50 mg PO twice per day on days 1 to 28
**1.50 m2 or more: 60 mg PO twice per day on days 1 to 28
42-day cycles
===References===
#GRAPE: Ioka T, Ueno M, Ueno H, Park JO, Chang HM, Sasahira N, Kanai M, Chung IJ, Ikeda M, Nakamori S, Mizuno N, Omuro Y, Yamaguchi T, Hara H, Sugimori K, Furuse J, Maguchi H, Furukawa M, Fukuzawa K, Kim JS, Yukisawa S, Takeuchi M, Okusaka T, Boku N, Hyodo I. TAS-118 (S-1 plus leucovorin) versus S-1 in patients with gemcitabine-refractory advanced pancreatic cancer: a randomised, open-label, phase 3 study (GRAPE trial). Eur J Cancer. 2019 Jan;106:78-88. Epub 2018 Nov 22. link to original article EuroPMC
#MPACA-3: Go SI, Lee SC, Bae WK, Zang DY, Lee HW, Jang JS, Ji JH, Kim JH, Park S, Sym SJ, Yang Y, Jeon SY, Hwang IG, Oh SY, Kang JH. Modified FOLFIRINOX versus S-1 as second-line chemotherapy in gemcitabine-failed metastatic pancreatic cancer patients: A randomised controlled trial (MPACA-3). Eur J Cancer. 2021 Nov;157:21-30. Epub 2021 Aug 28. link to original article EuroPMC KCT0003534
=Metastatic disease, 5-FU-refractory=
==Gemcitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Rothenberg et al. 1996a	1992-1994 	Phase 2 (RT)
====Chemotherapy====
*Gemcitabine (Gemzar) as follows:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
**Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
8-week course, then 28-day cycles
===References===
#Rothenberg ML, Moore MJ, Cripps MC, Andersen JS, Portenoy RK, Burris HA 3rd, Green MR, Tarassoff PG, Brown TD, Casper ES, Storniolo AM, Von Hoff DD. A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol. 1996 Apr;7(4):347-53. link to original article EuroPMC
#PRODIGE 65: NCT03943667
=Metastatic disease, second-line=
==Capecitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hurwitz et al. 2018 (JANUS 1)	2014-2016 	Phase 3 (C)	Capecitabine & Ruxolitinib	Did not meet primary endpoint of OSMedian OS: 93 vs 89 days(HR 1.03, 95% CI 0.80-1.34)
Hurwitz et al. 2018 (JANUS 2)	2014-2016 	Phase 3 (C)	Capecitabine & Ruxolitinib	Did not meet primary endpoint of OSMedian OS: 149 vs 108 days(HR 0.63, 95% CI 0.35-1.13)
Note: the same publication reports on both of these studies.
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
21-day cycles
===References===
#JANUS 1: Hurwitz H, Van Cutsem E, Bendell J, Hidalgo M, Li CP, Salvo MG, Macarulla T, Sahai V, Sama A, Greeno E, Yu KH, Verslype C, Dawkins F, Walker C, Clark J, O'Reilly EM. Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies. Invest New Drugs. 2018 Aug;36(4):683-695. Epub 2018 Mar 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02117479
#JANUS 2: Hurwitz H, Van Cutsem E, Bendell J, Hidalgo M, Li CP, Salvo MG, Macarulla T, Sahai V, Sama A, Greeno E, Yu KH, Verslype C, Dawkins F, Walker C, Clark J, O'Reilly EM. Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies. Invest New Drugs. 2018 Aug;36(4):683-695. Epub 2018 Mar 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02119663
==Gemcitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
De La Fouchardière et al. 2024 (GEMPAX)	2019-06 to 2021-03 	Phase 3 (C)	Gemcitabine & Paclitaxel	Did not meet primary endpoint of OSMedian OS: 5.9 vs 6.4 mo(HR 1.15, 95% CI 0.83-1.59)
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Prior treatment criteria====
*FOLFIRINOX, with progression or intolerance
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 to 40 minutes once per day on days 1, 8, 15
28-day cycles
===References===
#GEMPAX: De La Fouchardière C, Malka D, Cropet C, Chabaud S, Raimbourg J, Botsen D, Launay S, Evesque L, Vienot A, Perrier H, Jary M, Rinaldi Y, Coutzac C, Bachet JB, Neuzillet C, Williet N, Desgrippes R, Grainville T, Aparicio T, Peytier A, Lecomte T, Roth GS, Thirot-Bidault A, Lachaux N, Bouché O, Ghiringhelli F. Gemcitabine and Paclitaxel Versus Gemcitabine Alone After 5-Fluorouracil, Oxaliplatin, and Irinotecan in Metastatic Pancreatic Adenocarcinoma: A Randomized Phase III PRODIGE 65-UCGI 36-GEMPAX UNICANCER Study. J Clin Oncol. 2024 Mar 20;42(9):1055-1066. Epub 2024 Jan 17. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03943667
==Sotorasib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Strickler et al. 2022 (CodeBreaK100pancreatic)	2019-2021 	Phase 1/2
====Biomarker eligibility criteria====
*KRAS p.G12C mutation
====Targeted therapy====
*Sotorasib (Lumakras) 960 mg PO once per day
Continued indefinitely
===References===
#CodeBreaK100pancreatic: Strickler JH, Satake H, George TJ, Yaeger R, Hollebecque A, Garrido-Laguna I, Schuler M, Burns TF, Coveler AL, Falchook GS, Vincent M, Sunakawa Y, Dahan L, Bajor D, Rha SY, Lemech C, Juric D, Rehn M, Ngarmchamnanrith G, Jafarinasabian P, Tran Q, Hong DS. Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer. N Engl J Med. 2023 Jan 5;388(1):33-43. Epub 2022 Dec 21. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT03600883
Category:Pancreatic cancer regimens
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Category:Gastrointestinal cancers