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Note: this page contains regimens for pancreatic adenocarcinoma which were not tested in biomarker-specific populations. The following links will take you to biomarker- and histology-specific subpages:

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


ESMO


French Intergroup


NCCN


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 superior 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

Chemotherapy

28-day cycle for 6 cycles

References

  1. 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 PubMed 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 & RT
2. 5-FU & RT/FULV 		Seems to have superior OS1 (primary endpoint)
3. Observation Superior 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 OS
Median 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 OS
Median 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

Chemotherapy

28-day cycle for 6 cycles

References

  1. 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 PubMed
    1. 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 PubMed
  2. 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 PubMed NCT00058201
  3. 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 PubMed 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 Did not meet primary endpoint of OS2

2Reported efficacy is based on the 2011 update.

Preceding treatment

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

  1. 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 PubMed NCT00003216
    1. Update: Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the US Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26. Epub 2011 Mar 10. link to original article link to PMC article PubMed


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 Superior DFS1 (primary endpoint)
Median DFS: 21.4 vs 12.8 mo
(HR 0.66, 95% CI 0.54-0.82)

Superior 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

Chemotherapy

14-day cycle for 12 cycles

References

  1. 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 PubMed NCT01526135
    1. 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 PubMed
  2. 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

Chemotherapy

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 Seems to have superior 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 OS
Median 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 OS
Median 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 Inferior OS
Sinn et al. 2017 (CONKO-005) 2008-2013 Phase 3 (C) Erlotinib & Gemcitabine Did not meet primary endpoint of DFS
Median 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 inferior OS
Conroy et al. 2018 (NCIC-CTG PA.6) 2012-2016 Phase 3 (C) mFOLFIRINOX Inferior OS
Tempero et al. 2023 (APACT) 2014-04 to 2016-04 Phase 3 (C) Gemcitabine & nab-Paclitaxel Did not meet primary endpoint of DFS
Median 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.
Note: Treatment starts day 10 to 42 after surgery or after wound is healed.

Preceding treatment

Chemotherapy

28-day cycle for up to 6 cycles

References

  1. 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 PubMed ISRCTN34802808
    1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed
  4. 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 PubMed NCT00058201
  5. 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 PubMed UMIN000000655
  6. 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 PubMed ISRCTN96397434
  7. 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 PubMed DRKS00000247
  8. 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 PubMed NCT01526135
    1. 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 PubMed
  9. 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 PubMed NCT01964430
  10. 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 Did not meet primary endpoint of OS1

1Reported efficacy is based on the 2011 update.

Preceding treatment

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

  1. 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 PubMed NCT00003216
    1. Update: Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the US Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26. Epub 2011 Mar 10. link to original article link to PMC article PubMed


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 Superior 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

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

  1. 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 PubMed UMIN000000655


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

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

  1. 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 PubMed


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 superior OS24 (primary endpoint)

Chemotherapy

Radiotherapy

6-week course

Subsequent treatment


Regimen variant #2, 500 mg/m2

Study Dates of enrollment Evidence
Landry et al. 2010 (ECOG E1200) 2003-2005 Phase 2

Chemotherapy

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

Chemotherapy

Radiotherapy

6-week course


Regimen variant #4, 1000 mg/m2

Study Dates of enrollment Evidence
Takahashi et al. 2013 Not reported Phase 2

Chemotherapy

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

Chemotherapy

Radiotherapy

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 superior OS (primary endpoint)1
Median 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

References

  1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed UMIN000001804
  4. 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 PubMed
  5. 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 PubMed NCT01458717
  6. 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 PubMed EudraCT 2012-003181-40
    1. 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 PubMed
  7. 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

  1. 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 PubMed


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

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

Radiotherapy

  • Proton radiotherapy of 2500 cGyE in 5 treatments OR Intensity modulated radiotherapy (IMRT) of 3000 cGy in 10 fractions

One course

References

  1. 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 PubMed NCT01591733


mFOLFIRINOX

mFOLFIRINOX: modified FOLinic acid (Leucovorin), Fluorouracil, IRINotecan, OXaliplatin

Regimen variant #1

Study Dates of enrollment Evidence
Awaiting publication (Alliance A021501) 2016-2020 Randomized Phase 2

Note: comparison was to historic control. Dosing details are from ASCO abstract 377 (2021).

Chemotherapy

14-day cycle for 8 cycles

Subsequent treatment


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

Supportive therapy

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

  1. 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 PubMed NCT01836432
  2. 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 PubMed
  3. 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

Supportive therapy

14-day cycle for 4 to 8 cycles, followed by complete restaging

Subsequent treatment

References

  1. 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 PubMed


Induction therapy for locally advanced disease, unresectable

Capecitabine monotherapy

Regimen

Study Dates of enrollment Evidence
Cartwright et al. 2002 1998-1999 Phase 2

Chemotherapy

21-day cycle for up to 18 cycles (1 year)

References

  1. 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 PubMed


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

Chemotherapy

28-day cycle for 4 cycles

Subsequent treatment


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

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 superior 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

  1. 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 PubMed NCT00026338
  2. 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 PubMed 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 Superior OS
Herman et al. 2013 (GV-001.004) 2005-2010 Phase 3 (C) Fluorouracil & RT with TNFerade Did not meet primary endpoint of OS
Median 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

References

  1. 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 PubMed
  2. 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 PubMed 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

28-day cycle for 4 cycles

Subsequent treatment


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

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 inferior OS
Chauffert et al. 2008 (FFCD/SFRO 2000-01) 2000-2005 Phase 3 (E-de-esc) CF & RT, then Gemcitabine Seems to have superior 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 inferior PFS
Loehrer et al. 2011 (ECOG E4201) 2003-2005 Phase 3 (C) Gemcitabine & RT Seems to have inferior OS

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

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

  1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed
  4. 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 PubMed NCT00416507
  5. 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 PubMed NCT00057876
  6. 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 PubMed NCT00634725
  7. 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 superior OS (primary endpoint)
Median OS: 11.1 vs 9.2 mo

Chemotherapy, induction

Radiotherapy

  • Concurrent radiation therapy, 180 cGy per fraction x 28 fractions, total dose of 5040 cGy

10-week course

Subsequent treatment


Regimen variant #2, 400 mg/m2

Study Dates of enrollment Evidence
Epelbaum et al. 2002 1997-1999 Phase 2

Preceding treatment

Chemotherapy

Radiotherapy

5.5-week course

Subsequent treatment

References

  1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed 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 superior PFS (secondary endpoint)
Median PFS: 5.8 vs 3.7 mo
(HR 0.78, 95% CI 0.59-0.99)

Chemotherapy

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

  1. 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 PubMed


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

References

  1. 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 PubMed


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

Chemotherapy

28-day cycle for up to 5 cycles

References

  1. 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 PubMed 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

Chemotherapy

28-day cycles

References

  1. 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 PubMed


Metastatic disease, first-line

Capecitabine monotherapy

Regimen

Study Dates of enrollment Evidence
Cartwright et al. 2002 1998-1999 Phase 2

Chemotherapy

21-day cycle for up to 18 cycles (1 year)

References

  1. 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 PubMed


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 OS
Median OS: 7.9 vs 8.4 mo
(HR 0.95, 98.25% CI 0.85-1.29)
2. GemCap x 2, then Tertomotide Might have superior OS
Median 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

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 superior 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 inferior OS (primary endpoint)
Median OS: 7.5 vs 11.3 mo

Chemotherapy

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 superior 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

21-day cycle for up to 8 cycles

References

  1. 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 PubMed NCT00030732
    1. 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 PubMed
  2. 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 PubMed NCT00032175
  3. 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 PubMed NCT00425360
  4. 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 PubMed
  5. 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 PubMed 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 superior TTP

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
    • 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 OS
Median 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

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 OS

Chemotherapy

28-day cycles

References

  1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed NCT00536614
  4. 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 PubMed 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

Chemotherapy

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 superior 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 OS
Median 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

  1. 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 PubMed NCT00026338
  2. 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 PubMed NCT01214720
  3. 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 PubMed NCT00440167
  4. 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 PubMed 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 inferior 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

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

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. FA
2. FAM 		Did not meet primary endpoint of OS
Cullinan et al. 1990 Not reported Phase 3 (C) 1. Mallinson regimen
2. 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

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

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 Inferior OS

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

28-day cycles

References

  1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed
  4. 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 PubMed
  5. 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 PubMed
  6. 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 PubMed 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 Superior OS (primary endpoint)
Median OS: 11.1 vs 6.8 mo
(HR 0.57, 95% CI 0.45-0.73) 		Superior 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 OS
Median 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

  1. 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 PubMed NCT00112658
    1. 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 PubMed
  2. 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 PubMed 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 OS
Median 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

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 Superior OS (secondary endpoint)

Superior clinical benefit response (primary endpoint)
Colucci et al. 2002 Not reported Phase 3 (C) GC Seems to have inferior TTP
Moore et al. 2003 (NCIC-CTG PA.1) 1997-1999 Phase 3 (C) Tanomastat Superior OS
Van Cutsem et al. 2004 (CR003976) 1999-2001 Phase 3 (C) Gemcitabine & Tipifarnib Did not meet primary endpoint of OS
Median 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 OS
Median OS: 6.6 vs 6.3 mo
(HR not reported)
Reni et al. 2005 2000-2003 Phase 3 (C) PEFG Inferior PFS4
Louvet et al. 2005 2001-2003 Phase 3 (C) GemOx Seems to have inferior PFS
Abou-Alfa et al. 2006 (MSKCC 02-011) 2001-2003 Phase 3 (C) Gemcitabine & Exatecan Did not meet primary endpoint of OS
Median 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 inferior OS
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%
Poplin et al. 2009 (ECOG E6201) 2003-2005 Phase 3 (C) 1. Gemcitabine; fixed dose rate Might have inferior OS
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 inferior OS
Colucci et al. 2010 (GIP-1) 2002-2007 Phase 3 (C) GC Did not meet primary endpoint of OS
Dahan et al. 2010 (FFCD 0301) 2003-2006 Phase 3 (C) LV5FU2-CDDP Did not meet primary endpoint of OS
Median 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 OS
Median 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 Inferior OS
Gonçalves et al. 2012 (BAYPAN) 2006-2009 Phase 3 (C) Gemcitabine & Sorafenib Did not meet primary endpoint of PFS
Median 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 OS
Median 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 Inferior OS
Deplanque et al. 2015 (AB07012) Not reported Phase 3 (C) Gemcitabine & Masitinib Did not meet primary endpoint of OS
Median 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 OS
Median OS: 8.95 vs 8.8 mo
(HR 0.83, 80.8% CI 0.65-1.05)

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 Might have inferior PFS
Berlin et al. 2002 (ECOG E2297) 1998-04 to 1999-11 Phase 3 (C) 5-FU & Gemcitabine Might have inferior OS
Oettle et al. 2005 (JMES) 2001-2003 Phase 3 (C) Gemcitabine & Pemetrexed Did not meet primary endpoint of OS
Median 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 OS
Median 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 OS
Median 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 OS
Median 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
2. Gemcitabine & S-1 Did not meet primary endpoint of OS
Lee et al. 2017 2007-2011 Phase 3 (C) GemCap Might have inferior OS
Catenacci et al. 2015 (UCCRC-8418) 2010-2012 Randomized Phase 1b/2 (C) Gemcitabine & Vismodegib Did not meet primary endpoint of PFS
Median 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 OS
Median 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 OS
Median 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

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 inferior OS (primary endpoint)

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

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 TTP
Median TTP: 3.6 vs 2.4 mo

Chemotherapy

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 superior OS (primary endpoint)
Median OS: 6.2 vs 4.9 mo
(HR 0.83, 95% CI 0.69-1.00)
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

  1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed
  4. 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 PubMed
  5. 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 PubMed NCT00005648
  6. 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 PubMed
  7. 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 PubMed
  8. 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 PubMed NCT00035035
  9. 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 PubMed
  10. 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 PubMed
  11. 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 PubMed
  12. 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 PubMed NCT00023972
  13. 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 PubMed NCT00026338
  14. 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 PubMed NCT00030732
    1. 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 PubMed
  15. 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 PubMed NCT00219557
  16. 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 PubMed NCT00058149
  17. 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 PubMed NCT00032175
  18. 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 PubMed NCT00813696
  19. 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 PubMed NCT00075686
  20. 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 PubMed NCT00088894
  21. 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 PubMed NCT00303758
  22. 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 PubMed NCT00471146
    1. 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 PubMed
  23. 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 PubMed NCT00112658
    1. 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 PubMed
  24. 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 PubMed NCT00541021
  25. 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 PubMed NCT00498225
    1. 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 PubMed
  26. 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 PubMed NCT00574275
  27. 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 PubMed NCT00844649
    1. 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 PubMed
    2. 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 PubMed
  28. 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 PubMed NCT00944463
  29. 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 PubMed NCT01231347
  30. 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 PubMed NCT00789633
  31. 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 PubMed NCT01360853
  32. 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 PubMed NCT01064622
  33. 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 PubMed
  34. 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 PubMed ISRCTN96397434
  35. 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 PubMed 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 superior PFS (primary 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
2. Gemcitabine; fixed dose rate Did not meet primary endpoint of OS

Chemotherapy

14-day cycles

References

  1. 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 PubMed
  2. 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 PubMed 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 Superior 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 OS
Median 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 OS
Median OS: 11.5 vs 11.2 mo
(HR 1.00, 95% CI 0.79-1.25)
Wainberg et al. 2023 (NAPOLI 3) 2020-02-19 to 2021-08-17 Phase 3 (C) NALIRIFOX Seems to have inferior OS

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

28-day cycles

References

  1. 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 PubMed NCT00398086
  2. 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 PubMed NCT00844649
    1. 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 PubMed
    2. 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 PubMed
  3. 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 PubMed NCT02715804
  4. 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 PubMed NCT02436668
  5. 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 PubMed NCT04083235
  6. CanStem111P: NCT02993731
  7. 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 superior OS (primary endpoint)
Median OS: 10.9 vs 8.5 mo
(RMST ratio 0.62, 95% CI 0.40-0.97)

Chemotherapy

Targeted therapy

8-week cycles

References

  1. 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 PubMed 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

21-day cycles

References

  1. 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 PubMed
  2. 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
  3. 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 PubMed


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 superior OS (primary endpoint)
Median OS: 11.1 vs 9.2 mo
(HR 0.83, 95% CI 0.70-0.99)

Chemotherapy

14-day cycles

References

  1. 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 PubMed 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)
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

  1. 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 PubMed NCT00498225
    1. 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 PubMed


Metastatic disease, gemcitabine-refractory

Capecitabine & Erlotinib

Regimen

Study Dates of enrollment Evidence
Kulke et al. 2007 Not reported Phase 2

Chemotherapy

Targeted therapy

21-day cycles

References

  1. 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 PubMed


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

  1. 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 PubMed


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 Inferior OS

Chemotherapy

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 Inferior OS
Wang-Gillam et al. 2015 (NAPOLI-1) 2012-01-11 to 2013-09-11 Phase 3 (C) 1. FULV & nanoliposomal Irinotecan Seems to have inferior OS1
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 PFS
Median 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

  1. 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 PubMed NCT00786058
  2. 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 PubMed NCT01494506
    1. 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 PubMed
    2. 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 PubMed
    3. 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 PubMed
  3. 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 PubMed NCT01121848
  4. 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 PubMed 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 Superior 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

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 superior OS1 (primary endpoint)
Median OS: 4.9 vs 4.2 mo
(HR 0.75, 95% CI 0.57-0.99)
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

  1. 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 PubMed NCT01494506
    1. 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 PubMed
    2. 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 PubMed
    3. 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 PubMed
  2. 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 PubMed 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

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

14-day cycles

References

  1. 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 PubMed NCT00786006
  2. 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 PubMed 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 Superior OS (primary endpoint)
Median OS: 9.2 vs 4.9 mo
(aHR 0.40, 95% CI 0.20-0.70)

Chemotherapy

14-day cycles

References

  1. 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 PubMed 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

14-day cycles

References

  1. 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 PubMed 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 OS
Median 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

14-day cycle for up to 12 cycles

References

  1. 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 PubMed NCT02923921


Irinotecan liposomal monotherapy

Regimen

Study Dates of enrollment Evidence
Ko et al. 2013 (PEP0208) 2009-2010 Phase 2

Chemotherapy

21-day cycles

References

  1. 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 PubMed 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 Superior 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 Superior 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

  1. 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 PubMed NCT00786058
  2. 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 PubMed NCT00786058


nab-Paclitaxel monotherapy

Regimen

Study Dates of enrollment Evidence
Hosein et al. 2013 2008-07 to 2009-04 Phase 2

Chemotherapy

28-day cycles

References

  1. 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 PubMed


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 OS
Median 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 Inferior OS

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

  1. 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 PubMed
  2. 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 PubMed 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

  1. 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 PubMed
  2. 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 OS
Median 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 OS
Median 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

21-day cycles

References

  1. 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 PubMed NCT02117479
  2. 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 PubMed 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 OS
Median 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

28-day cycles

References

  1. 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 PubMed 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

Continued indefinitely

References

  1. 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 PubMed NCT03600883


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