Pancreatic cancer
Section editor | |
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Eric I. Marks, MD Boston University Boston, MA |
45 regimens on this page
74 variants on this page
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Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: this page contains regimens for pancreatic adenocarcinoma which were not tested in biomarker-specific populations. The following links will take you to biomarker- and histology-specific subpages:
- Regimens for BRCA-mutated pancreatic cancer are here.
- Regimens for Pancreatic neuroendocrine tumor are here.
Guidelines
ASCO
- 2020: Sohal et al. Metastatic Pancreatic Cancer: ASCO Guideline Update
- 2017: Khorana et al. Potentially curable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline update PubMed
Older
- 2018: Sohal et al. Metastatic pancreatic cancer: ASCO Clinical Practice Guideline update PubMed
- 2016: Sohal et al. Metastatic pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline
- 2016: Balaban et al. Locally advanced, unresectable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline PubMed
ESMO
- 2019: Stjepanovic et al. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
- 2019: eUpdate – Cancer of the Pancreas Treatment Recommendations
- 2017: eUpdate – Cancer of the Pancreas Treatment Recommendations
- 2015: Ducreux et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2015) PubMed
NCCN
Older
- 2017: Tempero et al. Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology PubMed
- 2014: Tempero et al. Pancreatic Adenocarcinoma, Version 2.2014 PubMed
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 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
- Capecitabine (Xeloda) 1660 mg/m2/day PO on days 1 to 21 (frequency of dosing not specified)
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycle for 6 cycles
References
- ESPAC-4: Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW; European Study Group for Pancreatic Cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017 Mar 11;389(10073):1011-1024. Epub 2017 Jan 25. link to original article contains dosing details in abstract PubMed ISRCTN96397434
FULV
FULV: 5-FU & LeucoVorin (Folinic acid)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Neoptolemos et al. 2001 (ESPAC-1) | 1994-2000 | Phase 3 (E-esc) | 1. 5-FU/5-FU & RT 2. 5-FU & RT, then FULV |
Seems to have superior OS1 |
3. Observation | Superior OS1 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 |
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
- Fluorouracil (5-FU) 425 mg/m2 IV bolus once per day on days 1 to 5, given second
- Folinic acid (Leucovorin) 20 mg/m2 IV bolus once per day on days 1 to 5, given first
28-day cycle for 6 cycles
References
- ESPAC-1: Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C, Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A, Spooner D, Kerr DJ, Friess H, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001 Nov 10;358(9293):1576-85. link to original article PubMed
- 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 contains dosing details in manuscript PubMed
- 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 contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00058201
- CapRI: Schmidt J, Abel U, Debus J, Harig S, Hoffmann K, Herrmann T, Bartsch D, Klein J, Mansmann U, Jäger D, Capussotti L, Kunz R, Büchler MW. Open-label, multicenter, randomized phase III trial of adjuvant chemoradiation plus interferon alfa-2b versus fluorouracil and folinic acid for patients with resected pancreatic adenocarcinoma. J Clin Oncol. 2012 Nov 20;30(33):4077-83. Epub 2012 Sep 24. link to original article contains dosing details in manuscript PubMed ISRCTN62866759
Fluorouracil/Fluorouracil & RT
Fluorouracil/Fluorouracil & RT: Fluorouracil alternating with Fluorouracil & Radiation Therapy
Protocol
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Neoptolemos et al. 2001 (ESPAC-1) | 1994-2000 | Phase 3 (E=esc) | 1. FULV 2. Observation |
Seems to have inferior OS1 |
3. 5-FU & RT, then FULV | Not reported | |||
Regine et al. 2008 (RTOG 9704) | 1998-2002 | Phase 3 (C) | Gemcitabine/5-FU & RT | Did not meet primary endpoint of OS2 |
1Reported efficacy for ESPAC-1 is based on the 2004 update.
2Reported efficacy for RTOG 9704 is based on the 2011 update.
Preceding treatment
Chemotherapy, part 1
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion over 21 days, started on day 1 (total dose: 5000 mg/m2)
21-day course, followed in 1 to 2 weeks by:
Chemotherapy, part 2
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion throughout radiation therapy
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions, for a total dose of 50.4 Gy. The last 5.4 Gy of the 50.4 Gy is limited to the tumor bed.
6-week course, followed in 3 to 5 weeks by:
Chemotherapy, part 3
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion over 28 days, started on day 1 (total dose per cycle: 7000 mg/m2)
6-week cycle for 2 cycles
References
- ESPAC-1: Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C, Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A, Spooner D, Kerr DJ, Friess H, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001 Nov 10;358(9293):1576-85. link to original article PubMed
- 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 contains dosing details in manuscript PubMed
- RTOG 9704: Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5;299(9):1019-26. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00003216
- Update: Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the US Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26. Epub 2011 Mar 10. link to original article link to PMC article PubMed
mFOLFIRINOX
mFOLFIRINOX: modified FOLinic acid, 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
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1, given second
- Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1, given fourth
- Irinotecan (Camptosar) 150 mg/m2 IV over 90 minutes once on day 1, given third
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first
14-day cycle for 12 cycles
References
- NCIC-CTG PA.6: Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Choné L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Breysacher G, Di Fiore F, Cripps C, Kavan P, Texereau P, Bouhier-Leporrier K, Khemissa-Akouz F, Legoux JL, Juzyna B, Gourgou S, O'Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet JB; NCIC-CTG; Unicancer-GI–PRODIGE Group. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018 Dec 20;379(25):2395-2406. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT01526135
- Update: Conroy T, Castan F, Lopez A, Turpin A, Ben Abdelghani M, Wei AC, Mitry E, Biagi JJ, Evesque L, Artru P, Lecomte T, Assenat E, Bauguion L, Ychou M, Bouché O, Monard L, Lambert A, Hammel P; Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial. JAMA Oncol. 2022 Nov 1;8(11):1571-1578. Epub 2022 Sep 1. link to original article link to PMC article PubMed
- Alliance A021806: https://clinicaltrials.gov/ct2/show/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
- Gemcitabine & RT, then surgery
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 100 minutes once per day on days 1 & 8
21-day cycle for 5 cycles
Regimen variant #2, 3 out of 4 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oettle et al. 2007 (CONKO-001) | 1998-2004 | Phase 3 (E-esc) | Observation | 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 |
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
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for up to 6 cycles
References
- CONKO-001: Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007 Jan 17;297(3):267-77. link to original article contains dosing details in manuscript PubMed ISRCTN34802808
- Update: Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zülke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013 Oct 9;310(14):1473-81. link to original article PubMed
- 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 contains dosing details in abstract PubMed
- 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 contains dosing details in manuscript link to PMC article PubMed
- 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 contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00058201
- JASPAC 01: Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T, Ohashi Y; JASPAC 01 Study Group. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016 Jul 16;388(10041):248-57. Epub 2016 Jun 2. link to original article contains dosing details in manuscript PubMed UMIN000000655
- 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 contains dosing details in abstract PubMed ISRCTN96397434
- CONKO-005: Sinn M, Bahra M, Liersch T, Gellert K, Messmann H, Bechstein W, Waldschmidt D, Jacobasch L, Wilhelm M, Rau BM, Grützmann R, Weinmann A, Maschmeyer G, Pelzer U, Stieler JM, Striefler JK, Ghadimi M, Bischoff S, Dörken B, Oettle H, Riess H. CONKO-005: adjuvant chemotherapy with gemcitabine plus erlotinib versus gemcitabine alone in patients after R0 resection of pancreatic cancer: a multicenter randomized phase III trial. J Clin Oncol. 2017 Oct 10;35(29):3330-3337. Epub 2017 Aug 17. link to original article contains dosing details in abstract PubMed DRKS00000247
- NCIC-CTG PA.6: Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Choné L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Breysacher G, Di Fiore F, Cripps C, Kavan P, Texereau P, Bouhier-Leporrier K, Khemissa-Akouz F, Legoux JL, Juzyna B, Gourgou S, O'Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet JB; NCIC-CTG; Unicancer-GI–PRODIGE Group. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018 Dec 20;379(25):2395-2406. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT01526135
- Update: Conroy T, Castan F, Lopez A, Turpin A, Ben Abdelghani M, Wei AC, Mitry E, Biagi JJ, Evesque L, Artru P, Lecomte T, Assenat E, Bauguion L, Ychou M, Bouché O, Monard L, Lambert A, Hammel P; Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial. JAMA Oncol. 2022 Nov 1;8(11):1571-1578. Epub 2022 Sep 1. link to original article link to PMC article PubMed
- 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 contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT01964430
- NLG0405: https://clinicaltrials.gov/ct2/show/NCT01072981
Gemcitabine/Fluorouracil & RT
Gemcitabine/Fluorouracil & RT: Gemcitabine alternating with Fluorouracil & Radiation Therapy
Protocol
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Regine et al. 2008 (RTOG 9704) | 1998-2002 | Phase 3 (E-switch-ic) | 5-FU/5-FU & RT | Did not meet primary endpoint of OS1 |
1Reported efficacy is based on the 2011 update.
Preceding treatment
Chemotherapy, part 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
21-day course, followed in 1 to 2 weeks by:
Chemotherapy, part 2
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion throughout radiation therapy
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions, for a total dose of 50.4 Gy. The last 5.4 Gy of the 50.4 Gy is limited to the tumor bed.
6-week course, followed in 3 to 5 weeks by:
Chemotherapy, part 3
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 3 cycles
References
- RTOG 9704: Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5;299(9):1019-26. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00003216
- Update: Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the US Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26. Epub 2011 Mar 10. link to original article link to PMC article PubMed
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 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:
- BSA less than 1.25 m2: 40 mg PO twice per day on days 1 to 28
- BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO twice per day on days 1 to 28
- BSA 1.5 m2 or more: 60 mg PO twice per day on days 1 to 28
42-day cycle for up to 4 cycles
References
- 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 contains dosing details in manuscript PubMed UMIN000000655
Induction therapy for locally advanced disease, potentially resectable
Docetaxel, Gemcitabine, RT
DG & RT: Docetaxel, Gemcitabine, Radiation Therapy
Protocol
Study | Dates of enrollment | Evidence |
---|---|---|
Pipas et al. 2005 | 2002-2004 | Phase 2 |
Chemotherapy, part 1
- Docetaxel (Taxotere) 65 mg/m2 IV over 60 minutes once on day 1
- Gemcitabine (Gemzar) 4000 mg/m2 IV over 30 minutes once on day 1
14-day cycle for 3 cycles, followed immediately (day 43) by:
Chemotherapy, part 2
- Gemcitabine (Gemzar) 50 mg/m2 IV over 30 minutes once per day on either days 1, 4, 8, 11 or days 2, 5, 9, 12, completed 30 minutes to 2 hours prior to RT
Supportive therapy
- GI prophylaxis with a proton pump inhibitor
14-day cycle for 3 cycles
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions, for a total dose of 45 Gy to primary target volume. Then 5.4 Gy boost to secondary target volume of 1- to 1.5-cm margin on all sides, including proven nodal involvement. Total 50.4 Gy in 28 fractions.
6-week course
References
- Pipas JM, Barth RJ Jr, Zaki B, Tsapakos MJ, Suriawinata AA, Bettmann MA, Cates JM, Ripple GH, Sutton JE, Gordon SR, McDonnell CE, Perez RP, Redfield N, Meyer LP, Marshall JF, Cole BF, Colacchio TA. Docetaxel/Gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma. Ann Surg Oncol. 2005 Dec;12(12):995-1004. Epub 2005 Nov 1. link to original article contains dosing details in manuscript 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 | 2012-2014 | Phase 2/3 (E-esc) | No neoadjuvant therapy | Seems to have superior OS |
Chemotherapy
- Gemcitabine (Gemzar) 400 mg/m2 IV over 50 minutes once per day on days 1, 8, 15, 22, 29, 36
Radiotherapy
- Concurrent radiation therapy, 45 Gy in 25 fractions, then 9 Gy in 5 fractions
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
- Gemcitabine (Gemzar) 500 mg/m2 IV over 50 minutes once per day on days 1, 8, 15, 22, 29, 36
Radiotherapy
- Concurrent radiation therapy, 180 cGy x 22 with 3 cm margin to GTV then 180 cGy x 6 with 2 cm margin to GTV, total 50.4 Gy 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, 1000 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Takahashi et al. 2013 | NR in abstract | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycle for 3 cycles
Radiotherapy
- Concurrent radiation therapy, 2 Gy per fraction x 25 fractions, total dose of 50 Gy
5-week course
Subsequent treatment
- Restaging is performed 8 weeks after radiation complete (2 weeks after chemotherapy complete). Resection immediately thereafter, if feasible
Regimen variant #4, 1000 mg/m2, short course RT
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, part 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle, followed by:
Chemotherapy, part 2, concurrent RT
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
Radiotherapy
- Concurrent radiation therapy, 2.4 Gy in 3 weeks to the pancreatic tumor and suspicious lymph nodes
4-week course, followed in 4 weeks by: Surgical resection, followed by:
Chemotherapy, part 3
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 4 cycles
References
- ECOG E1200: Landry J, Catalano PJ, Staley C, Harris W, Hoffman J, Talamonti M, Xu N, Cooper H, Benson AB 3rd. Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. J Surg Oncol. 2010 Jun 1;101(7):587-92. link to original article contains dosing details in manuscript link to PMC article PubMed
- 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 contains dosing details in manuscript PubMed UMIN000001804
- 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 contains dosing details in manuscript PubMed
- 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
- 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
- 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 |
Chemotherapy
- Gemcitabine (Gemzar) 50 mg/m2 IV over 30 minutes once per day on days 1 & 4 or days 2 & 5, 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 on day 1
7-day cycle for 6 cycles
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 54 Gy in 28 fractions. Synchronously, PTV1 and PTV2 received 45 and 50.4 Gy, respectively.
Supportive therapy
- GI prophylaxis with a proton pump inhibitor during chemoradiotherapy
6-week course One month following therapy, patients were restaged with CT scan of chest/abdomen/pelvis. Patients deemed to be candidates for surgical resection were offered laparotomy ∼6 to 10 weeks after completion of neoadjuvant therapy.
References
- Pipas JM, Zaki BI, McGowan MM, Tsapakos MJ, Ripple GH, Suriawinata AA, Tsongalis GJ, Colacchio TA, Gordon SR, Sutton JE, Srivastava A, Smith KD, Gardner TB, Korc M, Davis TH, Preis M, Tarczewski SM, Mackenzie TA, Barth RJ Jr. Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma. Ann Oncol. 2012 Nov;23(11):2820-7. Epub 2012 May 9. link to original article contains dosing details in manuscript link to PMC article PubMed
FOLFIRINOX/modified FOLFIRINOX +/- Chemoradiation
mFOLFIRINOX: modified FOLinic acid, 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
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1, given second
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given fourth (total dose per cycle: 2800 mg/m2)
- Irinotecan (Camptosar) 180 mg/m2 IV over 90 minutes once on day 1, given third with the last 90 minutes of leucovorin; that is, irinotecan starts 30 minutes after the start of leucovorin
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first
Supportive therapy
- Pegfilgrastim (Neulasta) 6 mg SC once on day 4
14-day cycle for 4 to 8 cycles, followed by restaging with CT scan. If tumor was resectable (no vascular involvement), they received short-course proton chemoradiotherapy:
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 PO twice per day, Monday – Friday for 2 weeks
Radiotherapy
- Proton radiotherapy of 25 GyE in 5 treatments OR Intensity modulated radiotherapy (IMRT) of 30 Gy in 10 fractions
One course
References
- MGH 11-328: Murphy JE, Wo JY, Ryan DP, Jiang W, Yeap BY, Drapek LC, Blaszkowsky LS, Kwak EL, Allen JN, Clark JW, Faris JE, Zhu AX, Goyal L, Lillemoe KD, DeLaney TF, Fernández-Del Castillo C, Ferrone CR, Hong TS. Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial. JAMA Oncol. 2018 Jul 1;4(7):963-969. link to original article contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT01591733
mFOLFIRINOX
mFOLFIRINOX: modified FOLinic acid, Fluorouracil, IRINotecan, OXaliplatin
Regimen
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
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1
- Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1
- Irinotecan (Camptosar) 180 mg/m2 IV over 90 minutes once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
14-day cycle for 8 cycles
Subsequent treatment
- Pancreatectomy, then mFOLFOX6 x 4
References
- PILLAR: Hewitt DB, Nissen N, Hatoum H, Musher B, Seng J, Coveler AL, Al-Rajabi R, Yeo CJ, Leiby B, Banks J, Balducci L, Vaccaro G, LoConte N, George TJ, Brenner W, Elquza E, Vahanian N, Rossi G, Kennedy E, Link C, Lavu H. A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer. Ann Surg. 2022 Jan 1;275(1):45-53. link to original article PubMed https://clinicaltrials.gov/ct2/show/NCT01836432
- Alliance A021501: https://clinicaltrials.gov/ct2/show/NCT02839343
mFOLFIRINOX, Gemcitabine, RT
mFOLFIRINOX, Gemcitabine, RT: modified FOLinic acid, Fluorouracil, IRINotecan, OXaliplatin, Gemcitabine, Radiation Therapy
Protocol variant #1
Study | Evidence |
---|---|
Blazer et al. 2015 | Retrospective |
Chemotherapy, mFOLFIRINOX portion
- Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1
- Irinotecan (Camptosar) 165 mg/m2 IV over 90 minutes once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 to 4 hours once on day 1
Supportive therapy, mFOLFIRINOX portion
- Pegfilgrastim (Neulasta) 6 mg SC once on day 4
14-day cycle for 4 to 8 cycles Followed by complete restaging. If tumor localized but still not resectable, chemoradiotherapy was administered:
Chemotherapy, consolidation portion
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
Radiotherapy, consolidation portion
- External beam radiotherapy was 36 Gy in 15 daily fractions
3-week course
Protocol variant #2
Study | Evidence |
---|---|
Hosein et al. 2012 | Retrospective |
Note: Protocol followed "per ACCORD-11 trial."
Chemotherapy, mFOLFIRINOX portion
- Folinic acid (Leucovorin) 400 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
- Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
Supportive therapy, mFOLFIRINOX portion
- Filgrastim (Neupogen) was given at the discretion of the treating physician
14-day cycle until maximum response or intolerance
Subsequent treatment
- Hosein et al. 2012, resectable patients by imaging criteria were offered: Surgery, then adjuvant chemoradiotherapy
- Hosein et al. 2012, unresectable patients were offered: Chemoradiotherapy, then surgery (if they became resectable):
Chemotherapy
- Gemcitabine (Gemzar) 600 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
Radiotherapy
- External beam radiotherapy at 50.4 Gy in 28 fractions.
6-week course
References
- 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
- 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. 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
- Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for up to 18 cycles (1 year)
References
- Cartwright TH, Cohn A, Varkey JA, Chen YM, Szatrowski TP, Cox JV, Schulz JJ. Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol. 2002 Jan 1;20(1):160-4. link to original article contains dosing details in manuscript 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
- Erlotinib (Tarceva) 100 mg PO once per day
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 4 cycles
Subsequent treatment
- GERCOR LAP07, patients without progression: Erlotinib & Gemcitabine x 2 (6 total) versus Capecitabine, Erlotinib, RT
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
- Cycles 5 & 6: 150 mg PO once per day
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 6 cycles
Regimen variant #3, gemcitabine lead-in, erlotinib 100 mg/day
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | |
---|---|---|---|---|---|
Moore et al. 2007 (NCIC-CTG PA.3)
|
2001-2003 | Phase 3 (E-RT-esc) | Gemcitabine | Seems to have superior OS Median OS: 6.2 vs 5.9 mo (HR 0.82, 95% CI 0.69-0.99) |
Targeted therapy
- Erlotinib (Tarceva) 100 mg PO once per day
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 cycle for 1 cycle, 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) 150 mg PO once per day
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 cycle for 1 cycle, then 28-day cycles
References
- NCIC-CTG PA.3: Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. Epub 2007 Apr 23. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00026338
- GERCOR LAP07: Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; GERCOR. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00634725
Fluorouracil & RT
Fluorouracil & RT: Fluorouracil & Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moertel et al. 1981 | NR | 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 day 1 (total dose per cycle: 1000 mg/m2)
7-day cycle for 5 cycles
Radiotherapy
- Concurrent radiation therapy: 1.8 Gy fractions x 25 fractions, for a total dose of 45 Gy, followed by 1.8 Gy x 3 fractions boost to the tumor bed (total dose of 50.4 Gy)
5.5-week course
Subsequent treatment
- GV-001.004: Gemcitabine or Erlotinib & Gemcitabine maintenance, starting four weeks after chemoradiotherapy
References
- Moertel CG, Frytak S, Hahn RG, O'Connell MJ, Reitemeier RJ, Rubin J, Schutt AJ, Weiland LH, Childs DS, Holbrook MA, Lavin PT, Livstone E, Spiro H, Knowlton A, Kalser M, Barkin J, Lessner H, Mann-Kaplan R, Ramming K, Douglas HO Jr, Thomas P, Nave H, Bateman J, Lokich J, Brooks J, Chaffey J, Corson JM, Zamcheck N, Novak JW; Gastrointestinal Tumor Study Group. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer. 1981 Oct 15;48(8):1705-10. link to original article PubMed
- 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 contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00051467
Gemcitabine monotherapy
Regimen variant #1, 3 out of 4 weeks x 4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hammel et al. 2016 (GERCOR LAP07) | 2008-2011 | Phase 3 (C) | See link | See link |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 4 cycles
Subsequent treatment
- GERCOR LAP07, patients without progression: Gemcitabine x 2 (6 total) versus Capecitabine & RT
Regimen variant #2, 3 out of 4 weeks x 6
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hammel et al. 2016 (GERCOR LAP07) | 2008-2011 | Phase 3 (C) | See link | See link |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 6 cycles
Regimen variant #3, 8-week lead-in ("Burris regimen")
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cantore et al. 2004 | 1997-2001 | Phase 3 (C) | Intraarterial FLEC | Seems to have inferior OS |
Chauffert et al. 2008 (FFCD/SFRO 2000-01) | 2000-2005 | Phase 3 (E-de-esc) | CF & RT, then Gemcitabine | Might have superior OS |
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 cycle for 1 cycle, then 28-day cycles
Subsequent treatment
- Louvet et al. 2005: 5-FU & RT consolidation was recommended but not mandated
References
- 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 contains dosing details in abstract PubMed
- 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 contains dosing details in manuscript PubMed
- 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 contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00416507
- ECOG E4201: Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011 Nov 1;29(31):4105-12. Epub 2011 Oct 3. link to original article contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00057876
- GERCOR LAP07: Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; GERCOR. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00634725
- AB12005: https://clinicaltrials.gov/ct2/show/NCT03766295
Gemcitabine & RT
Gemcitabine & RT: Gemcitabine & Radiation Therapy
Protocol 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 |
Chemotherapy, induction
- Gemcitabine (Gemzar) 600 mg/m2 IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy per fraction x 28 fractions, total dose of 50.4 Gy
5.5-week course, followed in 4 weeks by:
Chemotherapy, consolidation
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for up to 5 cycles
Protocol variant #2, 400 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Epelbaum et al. 2002 | 1997-1999 | Phase 2 |
Chemotherapy, part 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
Radiation planning during this phase, followed by:
Chemotherapy, part 2
- Gemcitabine (Gemzar) 400 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy 1.8 Gy x 28 fractions, total dose of 50.4 Gy
5.5-week course, followed by:
Chemotherapy, maintenance
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
References
- Epelbaum R, Rosenblatt E, Nasrallah S, Faraggi D, Gaitini D, Mizrahi S, Kuten A. Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J Surg Oncol. 2002 Nov;81(3):138-43. link to original article contains dosing details in manuscript PubMed
- 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
- 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 contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/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 Median PFS: 5.8 vs 3.7 mo (HR 0.78, 95% CI 0.59-0.99) |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 100 minutes once on day 1
- Oxaliplatin (Eloxatin) 100 mg/m2 IV over 2 hours once on day 2
14-day cycle for at least 6 cycles
Subsequent treatment
- Subsequent chemoradiotherapy (45 Gy in 25 fractions for 5 weeks, associated with a daily FU 250 mg/m2 continuous infusion, and a boost of 10 Gy in 8 fractions restricted to the initial tumor volume) was recommended but not mandated.
References
- Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A; GERCOR; GISCAD. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005 May 20;23(15):3509-16. link to original article contains dosing details in manuscript 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
- 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
Metastatic disease, first-line
Capecitabine monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Cartwright et al. 2002 | 1998-1999 | Phase 2 |
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for up to 18 cycles (1 year)
References
- Cartwright TH, Cohn A, Varkey JA, Chen YM, Szatrowski TP, Cox JV, Schulz JJ. Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol. 2002 Jan 1;20(1):160-4. link to original article contains dosing details in manuscript 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 & GV1001 | 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 GV1001 | 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
- Capecitabine (Xeloda) 830 mg/m2 PO twice per day on days 1 to 21
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 6 cycles
Regimen variant #2, q4wk indefinite
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2017 | 2007-2011 | Phase 3 (E-esc) | Gemcitabine | Might have superior OS Median OS: 10.3 vs 7.5 mo (HR 0.82, 95% CI 0.67-1.01) |
Chemotherapy
- Capecitabine (Xeloda) 830 mg/m2 PO twice per day on days 1 to 21
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Regimen variant #3, induction followed by maintenance
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cunningham et al. 2009 (CRUK GEM-CAP) | 2002-2005 | Phase 3 (E-esc) | Gemcitabine | Might have superior OS 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 cycle for 1 cycle, 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 OS |
Chemotherapy
- Capecitabine (Xeloda) 650 mg/m2 PO twice per day on days 1 to 14
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycle for up to 8 cycles
References
- SAKK 44/00-CECOG/PAN.1.3.001: Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W; Swiss Group for Clinical Cancer Research; Central European Cooperative Oncology Group. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol. 2007 Jun 1;25(16):2212-7. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00030732
- CBR/QoL analysis: Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Herrmann R; Central European Cooperative Oncology Group. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol. 2008 Aug 1;26(22):3695-701. link to original article contains dosing details in manuscript PubMed
- 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 contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00032175
- TeloVac: Middleton G, Silcocks P, Cox T, Valle J, Wadsley J, Propper D, Coxon F, Ross P, Madhusudan S, Roques T, Cunningham D, Falk S, Wadd N, Harrison M, Corrie P, Iveson T, Robinson A, McAdam K, Eatock M, Evans J, Archer C, Hickish T, Garcia-Alonso A, Nicolson M, Steward W, Anthoney A, Greenhalf W, Shaw V, Costello E, Naisbitt D, Rawcliffe C, Nanson G, Neoptolemos J. Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial. Lancet Oncol. 2014 Jul;15(8):829-40. Epub 2014 Jun 19. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00425360
- Lee HS, Chung MJ, Park JY, Bang S, Park SW, Kim HG, Noh MH, Lee SH, Kim YT, Kim HJ, Kim CD, Lee DK, Cho KB, Cho CM, Moon JH, Kim DU, Kang DH, Cheon YK, Choi HS, Kim TH, Kim JK, Moon J, Shin HJ, Song SY; Korean Society of Gastrointestinal Cancer. A randomized, multicenter, phase III study of gemcitabine combined with capecitabine versus gemcitabine alone as first-line chemotherapy for advanced pancreatic cancer in South Korea. Medicine (Baltimore). 2017 Jan;96(1):e5702. link to original article contains dosing details in manuscript link to PMC article PubMed
- KG 4/2015: https://clinicaltrials.gov/ct2/show/NCT02854072
Cisplatin & Gemcitabine (GC)
Regimen variant #1, 25/1000, weekly dosing
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colucci et al. 2002 | NR | Phase 3 (E-esc) | Gemcitabine | Seems to have superior TTP |
Colucci et al. 2010 (GIP-1) | 2002-2007 | Phase 3 (E-esc) | Gemcitabine | Did not meet primary endpoint of OS |
Note: Cisplatin is not given on day 22 of the first cycle; otherwise, the schedule is identical to the schedule for gemcitabine. Treatment in Colucci et al. 2002 is given for a total of 3 cycles (16 weeks).
Chemotherapy
- Cisplatin (Platinol) as follows, given first; 60 minutes prior to gemcitabine:
- Cycle 1: 25 mg/m2 IV once per day on days 1, 8, 15, 29, 36, 43
- Cycle 2 onwards: 25 mg/m2 IV 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 cycle for 1 cycle, then 28-day cycles
Regimen variant #2, 35/1000, 2 out of 3 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cascinu et al. 2008 (SPaCe-01) | 2005-2006 | Randomized Phase 2 (C) | GC & Cetuximab | Did not meet primary endpoint of ORR |
Chemotherapy
- Cisplatin (Platinol) 35 mg/m2 IV over 30 minutes once per day on days 1 & 8 (with 1500 mL NS)
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycles
Regimen variant #3, 50/1000, bi-weekly dosing
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Heinemann et al. 2006 | 1997-2002 | Phase 3 (E-esc) | Gemcitabine | Might have superior PFS |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV over 60 minutes once per day on days 1 & 15
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 15
28-day cycles
References
- Colucci G, Giuliani F, Gebbia V, Biglietto M, Rabitti P, Uomo G, Cigolari S, Testa A, Maiello E, Lopez M. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell'Italia Meridionale. Cancer. 2002 Feb 15;94(4):902-10. link to original article contains dosing details in abstract PubMed
- 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 contains dosing details in manuscript PubMed
- 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 contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00536614
- GIP-1: Colucci G, Labianca R, Di Costanzo F, Gebbia V, Cartenì G, Massidda B, Dapretto E, Manzione L, Piazza E, Sannicolò M, Ciaparrone M, Cavanna L, Giuliani F, Maiello E, Testa A, Pederzoli P, Falconi M, Gallo C, Di Maio M, Perrone F; GOIM; GISCAD; GOIRC. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol. 2010 Apr 1;28(10):1645-51. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00813696
Erlotinib & Gemcitabine
Regimen variant #1, no gemcitabine lead-in
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kordes et al. 2015 (AMCmedonc10/003) | 2010-2014 | Randomized Phase 2 (C) | Erlotinib, Gemcitabine, Metformin | Did not meet primary endpoint of OS6 |
Targeted therapy
- Erlotinib (Tarceva) 100 mg PO once per day
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen variant #2, gemcitabine lead-in, erlotinib 100 mg/day
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | |
---|---|---|---|---|---|
Moore et al. 2007 (NCIC-CTG PA.3)
|
2001-2003 | Phase 3 (E-RT-esc) | Gemcitabine | Seems to have superior OS Median OS: 6.2 vs 5.9 mo (HR 0.82, 95% CI 0.69-0.99) | |
Van Cutsem et al. 2009 (BO17706) | 2005-2006 | 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) 100 mg PO once per day
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 cycle for 1 cycle, 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 |
Note: due to low accrual in NCIC-CTG PA.3, the efficacy of this arm could not be determined.
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day
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 cycle for 1 cycle, then 28-day cycles
References
- NCIC-CTG PA.3: Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. Epub 2007 Apr 23. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00026338
- BO17706: Van Cutsem E, Vervenne WL, Bennouna J, Humblet Y, Gill S, Van Laethem JL, Verslype C, Scheithauer W, Shang A, Cosaert J, Moore MJ. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol. 2009 May 1;27(13):2231-7. Epub 2009 Mar 23. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT01214720
- AIO-PK0104: Heinemann V, Vehling-Kaiser U, Waldschmidt D, Kettner E, Märten A, Winkelmann C, Klein S, Kojouharoff G, Gauler TC, von Weikersthal LF, Clemens MR, Geissler M, Greten TF, Hegewisch-Becker S, Rubanov O, Baake G, Höhler T, Ko YD, Jung A, Neugebauer S, Boeck S. Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO-PK0104). Gut. 2013 May;62(5):751-9. Epub 2012 Jul 7. link to original article contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00440167
- AMCmedonc10/003: Kordes S, Pollak MN, Zwinderman AH, Mathôt RA, Weterman MJ, Beeker A, Punt CJ, Richel DJ, Wilmink JW. Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol. 2015 Jul;16(7):839-47. Epub 2015 Jun 8. link to original articlecontains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/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.
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.
Regimen variant #3, 500 mg/m2 intermittent with spacing
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cullinan et al. 1985 | NR | Phase 3 (E-de-esc) | 1. FA 2. FAM |
Did not meet primary endpoint of OS |
Cullinan et al. 1990 | NR | Phase 3 (C) | 1. Mallinson regimen 2. FAP |
Did not meet primary endpoint of OS |
Note: this is an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 to 5
28-day cycle for 2 cycles, then 35-day cycles
Regimen variant #4, 500 mg/m2 intermittent 35-day cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burch et al. 2000 | NR | 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.
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.
References
- Cullinan SA, Moertel CG, Fleming TR, Rubin JR, Krook JE, Everson LK, Windschitl HE, Twito DI, Marschke RF, Foley JF, Pfeifle DM, Barlow JF. A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma: fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA. 1985 Apr 12;253(14):2061-7. link to original article PubMed
- 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
- 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 contains dosing details in manuscript PubMed
- 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 contains dosing details in manuscript PubMed
- 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 contains dosing details in abstract PubMed
- 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 contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00003029
FOLFIRINOX
FOLFIRINOX: FOLinic acid, Fluorouracil, IRINotecan, OXaliplatin
FFX: Folinic acid, 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 Median OS: 11.1 vs 6.8 mo (HR 0.57, 95% CI 0.45-0.73) |
Superior QoL by EORTC QLQ-C30 |
Chemotherapy
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1, given second
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given fourth (total dose per cycle: 2800 mg/m2)
- Irinotecan (Camptosar) 180 mg/m2 IV over 90 minutes once on day 1, given third with the last 90 minutes of leucovorin; that is, irinotecan starts 30 minutes after the start of leucovorin
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first
14-day cycles
References
- PRODIGE 4/ACCORD 11: Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00112658
- HRQoL analysis: Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Boige V, Bérille J, Conroy T. Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol. 2013 Jan 1;31(1):23-9. Epub 2012 Dec 3. link to original article PubMed
- PANC003: https://clinicaltrials.gov/ct2/show/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 |
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.
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 |
Colucci et al. 2002 | NR | 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 |
Rocha Lima et al. 2004 | 2000-2001 | Phase 3 (C) | IG | Did not meet primary endpoint of OS Median OS: 6.6 vs 6.3 mo |
Reni et al. 2005 | 2000-2003 | Phase 3 (C) | PEFG | Seems to have inferior PFS |
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 |
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 OS |
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 |
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 (F) | 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) | NR | Phase 3 (C) | Gemcitabine & Masitinib | Did not meet primary endpoint of OS |
Middleton et al. 2017 (ViP) | 2011-2013 (C) | 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
- In Burris et al. 1997, patients with grade 2 or lower toxicities could have had doses increased to 1250 mg/m2
8-week cycle for 1 cycle, then 28-day cycles
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) | 1998-1999 | 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 | Randomized Phase 2 (C) | Gemcitabine & Axitinib | Did not meet primary endpoint of OS |
Kindler et al. 2011 (A4061028) | 2007-2008 | 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 |
Fuchs et al. 2015 (GAMMA) | 2011-2012 | Randomized Phase 1b/2 (C) | Gemcitabine & Ganitumab | Did not meet primary endpoint of OS |
O'Neil et al. 2015 (ONTRAC) | 2011-2013 | Phase 2/3 (C) | Gemcitabine & Rigosertib | 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
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Regimen variant #4, 1000 mg/m2, 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 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
21-day cycles
Regimen variant #5, 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 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
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- 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 contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00219557
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- 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 contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00032175
- GIP-1: Colucci G, Labianca R, Di Costanzo F, Gebbia V, Cartenì G, Massidda B, Dapretto E, Manzione L, Piazza E, Sannicolò M, Ciaparrone M, Cavanna L, Giuliani F, Maiello E, Testa A, Pederzoli P, Falconi M, Gallo C, Di Maio M, Perrone F; GOIM; GISCAD; GOIRC. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol. 2010 Apr 1;28(10):1645-51. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00813696
- SWOG S0205: Philip PA, Benedetti J, Corless CL, Wong R, O'Reilly EM, Flynn PJ, Rowland KM, Atkins JN, Mirtsching BC, Rivkin SE, Khorana AA, Goldman B, Fenoglio-Preiser CM, Abbruzzese JL, Blanke CD. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol. 2010 Aug 1;28(22):3605-10. Epub 2010 Jul 6. link to original article contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00075686
- CALGB 80303: Kindler HL, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H, Innocenti F, Mulcahy MF, O'Reilly E, Wozniak TF, Picus J, Bhargava P, Mayer RJ, Schilsky RL, Goldberg RM. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol. 2010 Aug 1;28(22):3617-22. Epub 2010 Jul 6. link to original article link to PMC article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00088894
- FFCD 0301: Dahan L, Bonnetain F, Ychou M, Mitry E, Gasmi M, Raoul JL, Cattan S, Phelip JM, Hammel P, Chauffert B, Michel P, Legoux JL, Rougier P, Bedenne L, Seitz JF; Fédération Francophone de Cancérologie Digestive. Combination 5-fluorouracil, folinic acid and cisplatin (LV5FU2-CDDP) followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: final results of a randomised strategic phase III trial (FFCD 0301). Gut. 2010 Nov;59(11):1527-34. link to original article link to PMC article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00303758
- A4061028: Kindler HL, Ioka T, Richel DJ, Bennouna J, Létourneau R, Okusaka T, Funakoshi A, Furuse J, Park YS, Ohkawa S, Springett GM, Wasan HS, Trask PC, Bycott P, Ricart AD, Kim S, Van Cutsem E. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study. Lancet Oncol. 2011 Mar;12(3):256-62. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00471146
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- 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 contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00541021
- GEST: Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013 May 1;31(13):1640-8. Epub 2013 Apr 1. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00498225
- Update: Okusaka T, Miyakawa H, Fujii H, Nakamori S, Satoh T, Hamamoto Y, Ito T, Maguchi H, Matsumoto S, Ueno H, Ioka T, Boku N, Egawa S, Hatori T, Furuse J, Mizumoto K, Ohkawa S, Yamaguchi T, Yamao K, Funakoshi A, Chen JS, Cheng AL, Sato A, Ohashi Y, Tanaka M; GEST group. Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer. J Cancer Res Clin Oncol. 2017 Jun;143(6):1053-1059. Epub 2017 Feb 16. link to original article link to PMC article PubMed
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- 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 contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00844649
- Update: Goldstein D, El-Maraghi RH, Hammel P, Heinemann V, Kunzmann V, Sastre J, Scheithauer W, Siena S, Tabernero J, Teixeira L, Tortora G, Van Laethem JL, Young R, Penenberg DN, Lu B, Romano A, Von Hoff DD. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst. 2015 Jan 31;107(2). link to original article PubMed
- 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
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- 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 contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT01231347
- AB07012: Deplanque G, Demarchi M, Hebbar M, Flynn P, Melichar B, Atkins J, Nowara E, Moyé L, Piquemal D, Ritter D, Dubreuil P, Mansfield CD, Acin Y, Moussy A, Hermine O, Hammel P. A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer. Ann Oncol. 2015 Jun;26(6):1194-200. Epub 2015 Apr 9. link to original article link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00789633
- ONTRAC: O'Neil BH, Scott AJ, Ma WW, Cohen SJ, Leichman L, Aisner DL, Menter AR, Tejani MA, Cho JK, Granfortuna J, Coveler AL, Olowokure OO, Baranda JC, Cusnir M, Phillip 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 contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT01360853
- UCCRC-8418: Catenacci DV, Junttila MR, Karrison T, Bahary N, Horiba MN, Nattam SR, Marsh R, Wallace J, Kozloff M, Rajdev L, Cohen D, Wade J, Sleckman B, Lenz HJ, Stiff P, Kumar P, Xu P, Henderson L, Takebe N, Salgia R, Wang X, Stadler WM, de Sauvage FJ, Kindler HL. Randomized phase Ib/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer. J Clin Oncol. 2015 Dec 20;33(36):4284-92. Epub 2015 Nov 2. link to original article contains dosing details in supplement link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT01064622
- Lee HS, Chung MJ, Park JY, Bang S, Park SW, Kim HG, Noh MH, Lee SH, Kim YT, Kim HJ, Kim CD, Lee DK, Cho KB, Cho CM, Moon JH, Kim DU, Kang DH, Cheon YK, Choi HS, Kim TH, Kim JK, Moon J, Shin HJ, Song SY; Korean Society of Gastrointestinal Cancer. A randomized, multicenter, phase III study of gemcitabine combined with capecitabine versus gemcitabine alone as first-line chemotherapy for advanced pancreatic cancer in South Korea. Medicine (Baltimore). 2017 Jan;96(1):e5702. link to original article contains dosing details in manuscript link to PMC article PubMed
- 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 contains dosing details in abstract PubMed ISRCTN96397434
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 |
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
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 100 minutes once on day 1
- Oxaliplatin (Eloxatin) 100 mg/m2 IV over 2 hours once on day 2
14-day cycles
References
- Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A; GERCOR; GISCAD. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005 May 20;23(15):3509-16. link to original article contains dosing details in manuscript PubMed
- 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 contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/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 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 cycle for 1 cycle, 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-NR | Phase 1/2 | ||
Tempero et al. 2021 (RESOLVE) | 2015-NR | Phase 3 (C) | Ibrutinib, Gemcitabine, nab-Paclitaxel | Did not meet primary endpoint of OS |
Van Cutsem et al. 2020 (HALO 109-301) | 2016-2018 | Phase 3 (C) | AG & PEGPH20 | Did not meet primary endpoint of 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
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 125 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- CA040: Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011 Dec 1;29(34):4548-54. Epub 2011 Oct 3. link to original article contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00398086
- MPACT: Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. Epub 2013 Oct 16. link to original article contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00844649
- Update: Goldstein D, El-Maraghi RH, Hammel P, Heinemann V, Kunzmann V, Sastre J, Scheithauer W, Siena S, Tabernero J, Teixeira L, Tortora G, Van Laethem JL, Young R, Penenberg DN, Lu B, Romano A, Von Hoff DD. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst. 2015 Jan 31;107(2). link to original article PubMed
- 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
- 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 contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT02715804
- RESOLVE: Tempero M, Oh DY, Tabernero J, Reni M, Van Cutsem E, Hendifar A, Waldschmidt DT, Starling N, Bachet JB, Chang HM, Maurel J, Garcia-Carbonero R, Lonardi S, Coussens LM, Fong L, Tsao LC, Cole G Jr, James D, Macarulla T. Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study. Ann Oncol. 2021 May;32(5):600-608. Epub 2021 Feb 1. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT02436668
- CanStem111P: https://clinicaltrials.gov/ct2/show/NCT02993731
- GRASPANC 2018-01: https://clinicaltrials.gov/ct2/show/NCT03665441
GTX
GTX: Gemcitabine, Taxotere (Docetaxel), Xeloda (Capecitabine)
Regimen
Study | Evidence |
---|---|
Fine et al. 2007 | Retrospective |
Note: De Jesus-Acosta et al. 2012 lists 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, uses capecitabine at 750 mg/m2 PO twice per day. The 2009 ASCO abstract by Fine also lists this 750 mg/m2 PO twice per day (1500 mg/m2/day) dose.
Chemotherapy
- Gemcitabine (Gemzar) 750 mg/m2 IV over 75 minutes once per day on days 4 & 11
- Docetaxel (Taxotere) 30 mg/m2 IV once per day on days 4 & 11
- Capecitabine (Xeloda) 750 mg/m2 PO twice per day on days 1 to 14
21-day cycles
References
- Retrospective: Fine RL, Fogelman DR, Schreibman SM, Desai M, Sherman W, Strauss J, Guba S, Andrade R, Chabot J. The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis. Cancer Chemother Pharmacol. 2008 Jan;61(1):167-75. Epub 2007 Apr 18. link to original article contains dosing details in abstract PubMed
- Abstract: R. L. Fine, G. Moorer, W. Sherman, K. Chu, M. Maurer, J. Chabot, I. Postolov, J. Prowda, S. Schreibman, J. Levitz. Phase II trial of GTX chemotherapy in metastatic pancreatic cancer. 2009 ASCO Annual Meeting abstract 4623. link to abstract content property of HemOnc.org
- Retrospective: De Jesus-Acosta A, Oliver GR, Blackford A, Kinsman K, Flores EI, Wilfong LS, Zheng L, Donehower RC, Cosgrove D, Laheru D, Le DT, Chung K, Diaz LA Jr. A multicenter analysis of GTX chemotherapy in patients with locally advanced and metastatic pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2012 Feb;69(2):415-24. Epub 2011 Jul 29. link to original article contains dosing details in manuscript--with error as noted above link to PMC article PubMed
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 |
2. Gemcitabine & S-1 | Not reported |
Chemotherapy
- Tegafur, gimeracil, oteracil (S-1) by the following weight-based criteria:
- BSA less than 1.25 m2: 40 mg PO twice per day on days 1 to 28
- BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO twice per day on days 1 to 28
- BSA 1.5 m2 or more: 60 mg PO twice per day on days 1 to 28
42-day cycles
References
- GEST: Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013 May 1;31(13):1640-8. Epub 2013 Apr 1. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00498225
- Update: Okusaka T, Miyakawa H, Fujii H, Nakamori S, Satoh T, Hamamoto Y, Ito T, Maguchi H, Matsumoto S, Ueno H, Ioka T, Boku N, Egawa S, Hatori T, Furuse J, Mizumoto K, Ohkawa S, Yamaguchi T, Yamao K, Funakoshi A, Chen JS, Cheng AL, Sato A, Ohashi Y, Tanaka M; GEST group. Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer. J Cancer Res Clin Oncol. 2017 Jun;143(6):1053-1059. Epub 2017 Feb 16. link to original article link to PMC article PubMed
Metastatic disease, gemcitabine-refractory
Capecitabine & Erlotinib
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Kulke et al. 2007 | NR | Phase 2 |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 (rounded to the nearest 150 mg tablet) PO twice per day on days 1 to 14
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO on days 1 to 21
21-day cycles
References
- Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, Enzinger PC, Kwak EL, Muzikansky A, Lawrence C, Fuchs CS. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol. 2007 Oct 20;25(30):4787-92. link to original article contains dosing details in manuscript 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:
- Age less than 65 years old and ECOG performance status less than 2: 1000 mg/m2 PO twice per day on days 1 to 14
- Age greater than 65 years old and/or ECOG performance status greater than or equal to 2: 750 mg/m2 PO twice per day on days 1 to 14
- Oxaliplatin (Eloxatin) by the following age- and performance-based criteria:
- Age less than 65 years old and ECOG performance status less than 2: 130 mg/m2 IV over 2 hours once on day 1
- Age greater than 65 years old and/or ECOG performance status greater than or equal to 2: 110 mg/m2 IV over 2 hours once on day 1
21-day cycles
References
- Xiong HQ, Varadhachary GR, Blais JC, Hess KR, Abbruzzese JL, Wolff RA. Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer. 2008 Oct 15;113(8):2046-52. link to original article contains dosing details in manuscript PubMed
FULV
FULV: 5-FU & LeucoVorin (Folinic acid)
FF: Fluorouracil & Folinic acid
Regimen variant #1, 2000/200
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)
- Folinic acid (Leucovorin) 200 mg/m2 IV once per day on days 1, 8, 15, 22, given first
42-day cycles
Regimen variant #2, 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 |
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)
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1, given first
14-day cycles
References
- CONKO-003 part 2: Oettle H, Riess H, Stieler JM, Heil G, Schwaner I, Seraphin J, Görner M, Mölle M, Greten TF, Lakner V, Bischoff S, Sinn M, Dörken B, Pelzer U. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014 Aug 10;32(23):2423-9. Epub 2014 Jun 30. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00786058
- NAPOLI-1: Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT; NAPOLI-1 Study Group. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545-57. Epub 2015 Nov 29. Erratum in: Lancet. 2016 Feb 6;387(10018):536. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT01494506
- 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
- 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
- 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
- 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 contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT01121848
FULV & nanoliposomal Irinotecan
FULV & nanoliposomal Irinotecan: 5-FU, LeucoVorin (Folinic acid), nanoliposomal Irinotecan
Regimen
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
- Folinic acid (Leucovorin) 400 mg/m2 IV over 30 minutes once on day 1, given second
- Irinotecan liposome (Onivyde) 70 mg/m2 (irinotecan free base) IV over 90 minutes once on day 1, given first
- Per Wang-Gillam et al. 2015 (NAPOLI-1), 70 mg/m2 irinotecan free base is equivalent to 80 mg/m2 nanoliposomal irinotecan. According to the trial's ClinicalTrials.gov page: "The published dose of ONIVYDE was expressed as the irinotecan hydrochloride trihydrate until October 2015. It is now expressed as the irinotecan free base. Converting a dose based on irinotecan hydrochloride trihydrate to a dose based on irinotecan free base is accomplished by substituting the Molecular Weight of irinotecan hydrochloride trihydrate (677.19 g/mole) with the Molecular Weight of irinotecan free base (586.68 g/mole), which results in a conversion factor of 0.866. 80 mg/m2 dose of irinotecan hydrochloride trihydrate is equivalent to 70 mg/m2 of irinotecan free base."
14-day cycles
References
- NAPOLI-1: Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT; NAPOLI-1 Study Group. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545-57. Epub 2015 Nov 29. Erratum in: Lancet. 2016 Feb 6;387(10018):536. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT01494506
- 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
- 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
- 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
FOLFIRI
FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Zaniboni et al. 2012 (SLAP) | 2010-2011 | Phase 2 |
Chemotherapy
- Folinic acid (Leucovorin) 200 mg/m2 IV once per day on days 1 & 2
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1 & 2, then 600 mg/m2 IV continuous infusion over 22 hours after each bolus (total dose per cycle: 2000 mg/m2)
- Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
14-day cycles
Regimen variant #2, modified FOLFIRI.3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yoo et al. 2009 (AMC P 01) | 2007-2008 | Randomized Phase 2 (E-switch-ic) | mFOLFOX | Did not meet primary endpoint of OS6 |
Chemotherapy
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1
- Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 46 hours, started on day 1
- Irinotecan (Camptosar) 70 mg/m2 IV once per day on days 1 & 3, with day 3 dose given at end of 5-FU infusion
14-day cycles
References
- AMC P 01: Yoo C, Hwang JY, Kim JE, Kim TW, Lee JS, Park DH, Lee SS, Seo DW, Lee SK, Kim MH, Han DJ, Kim SC, Lee JL. A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer. 2009 Nov 17;101(10):1658-63. Epub 2009 Oct 13. link to original article contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00786006
- SLAP: Zaniboni A, Aitini E, Barni S, Ferrari D, Cascinu S, Catalano V, Valmadre G, Ferrara D, Veltri E, Codignola C, Labianca R. FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multicenter phase II study. Cancer Chemother Pharmacol. 2012 Jun;69(6):1641-5. Epub 2012 May 11. link to original article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT01543412
mFOLFIRINOX
mFOLFIRINOX: modified FOLinic acid, 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 Median OS: 9.2 vs 4.9 mo (aHR 0.40, 95% CI 0.20-0.70) |
Chemotherapy
- Folinic acid (Leucovorin) 400 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 1000 mg/m2 IV continuous infusion over 24 hours, started on day 1
- Irinotecan (Camptosar) 135 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 65 mg/m2 IV once on day 1
14-day cycles
References
- MPACA-3: Go SI, Lee SC, Bae WK, Zang DY, Lee HW, Jang JS, Ji JH, Kim JH, Park S, Sym SJ, Yang Y, Jeon SY, Hwang IG, Oh SY, Kang JH. Modified FOLFIRINOX versus S-1 as second-line chemotherapy in gemcitabine-failed metastatic pancreatic cancer patients: A randomised controlled trial (MPACA-3). Eur J Cancer. 2021 Nov;157:21-30. Epub 2021 Aug 28. link to original article PubMed KCT0003534
FOLFOX
FOLFOX: FOLinic acid, 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
- Folinic acid (Leucovorin) 400 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 2000 mg/m2 IV once per day on days 1 & 2
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycles
References
- AMC P 01: Yoo C, Hwang JY, Kim JE, Kim TW, Lee JS, Park DH, Lee SS, Seo DW, Lee SK, Kim MH, Han DJ, Kim SC, Lee JL. A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer. 2009 Nov 17;101(10):1658-63. Epub 2009 Oct 13. link to original article contains dosing details in abstract link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT00786006
mFOLFOX6
mFOLFOX6: modified FOLinic acid, 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 |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, given third, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours (total dose per cycle: 2800 mg/m2)
- Folinic acid (Leucovorin) 400 mg/m2 IV over 120 minutes once on day 1, given first
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycle for up to 12 cycles
References
- SEQUOIA: Hecht JR, Lonardi S, Bendell J, Sim HW, Macarulla T, Lopez CD, Van Cutsem E, Muñoz Martin AJ, Park JO, Greil R, Wang H, Hozak RR, Gueorguieva I, Lin Y, Rao S, Ryoo BY. Randomized Phase III Study of FOLFOX Alone or With Pegilodecakin as Second-Line Therapy in Patients With Metastatic Pancreatic Cancer That Progressed After Gemcitabine (SEQUOIA). J Clin Oncol. 2021 Apr 1;39(10):1108-1118. Epub 2021 Feb 8. link to original article contains dosing details in manuscript link to PMC article PubMed https://clinicaltrials.gov/ct2/show/NCT02923921
Irinotecan liposomal monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Ko et al. 2013 (PEP0208) | 2009-2010 | Phase 2 |
References
- PEP0208: Ko AH, Tempero MA, Shan YS, Su WC, Lin YL, Dito E, Ong A, Wang YW, Yeh CG, Chen LT. A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer. Br J Cancer. 2013 Aug 20;109(4):920-5. link to original article link to PMC article contains dosing details in abstract PubMed https://clinicaltrials.gov/ct2/show/NCT00813163
OLF
OLF: Oxaliplatin, Leucovorin (Folinic acid), Fluorouracil
OFF: Oxaliplatin, Fluorouracil, Folinic acid
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pelzer et al. 2011 (CONKO-003) | 2002-2003 | Phase 3 (E-esc) | Best supportive care | Superior OS |
Oettle et al. 2014 (CONKO-003 part 2) | 2004-2007 | Phase 3 (E-esc) | FULV | Superior OS 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
- Folinic acid (Leucovorin) 200 mg/m2 IV bolus once per day on days 1, 8, 15, 22, given second
- Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, given third (total dose per cycle: 8000 mg/m2)
42-day cycles
References
- CONKO-003: Pelzer U, Schwaner I, Stieler J, Adler M, Seraphin J, Dörken B, Riess H, Oettle H. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer. 2011 Jul;47(11):1676-81. Epub 2011 May 10. link to original article contains dosing details in manuscript--with error as noted above PubMed https://clinicaltrials.gov/ct2/show/NCT00786058
- CONKO-003 part 2: Oettle H, Riess H, Stieler JM, Heil G, Schwaner I, Seraphin J, Görner M, Mölle M, Greten TF, Lakner V, Bischoff S, Sinn M, Dörken B, Pelzer U. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014 Aug 10;32(23):2423-9. Epub 2014 Jun 30. link to original article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT00786058
nab-Paclitaxel monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Hosein et al. 2013 | NR in abstract | Phase 2 |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
References
- Hosein PJ, de Lima Lopes G Jr, Pastorini VH, Gomez C, Macintyre J, Zayas G, Reis I, Montero AJ, Merchan JR, Rocha Lima CM. A phase II trial of nab-paclitaxel as second-line therapy in patients with advanced pancreatic cancer. Am J Clin Oncol. 2013 Apr;36(2):151-6. Epub 2012 Feb 2. link to original article contains dosing details in abstract 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 |
Go et al. 2021 (MPACA-3) | 2017-2019 | Phase 3 (C) | mFOLFIRINOX | Inferior OS |
Chemotherapy
- Tegafur, gimeracil, oteracil (S-1) by the following weight-based criteria:
- BSA less than 1.25 m2: 40 mg PO twice per day on days 1 to 28
- BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO twice per day on days 1 to 28
- BSA 1.5 m2 or more: 60 mg PO twice per day on days 1 to 28
42-day cycles
References
- GRAPE: Ioka T, Ueno M, Ueno H, Park JO, Chang HM, Sasahira N, Kanai M, Chung IJ, Ikeda M, Nakamori S, Mizuno N, Omuro Y, Yamaguchi T, Hara H, Sugimori K, Furuse J, Maguchi H, Furukawa M, Fukuzawa K, Kim JS, Yukisawa S, Takeuchi M, Okusaka T, Boku N, Hyodo I. TAS-118 (S-1 plus leucovorin) versus S-1 in patients with gemcitabine-refractory advanced pancreatic cancer: a randomised, open-label, phase 3 study (GRAPE trial). Eur J Cancer. 2019 Jan;106:78-88. Epub 2018 Nov 22. link to original article PubMed
- 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 cycle for 1 cycle, then 28-day cycles
References
- Rothenberg ML, Moore MJ, Cripps MC, Andersen JS, Portenoy RK, Burris HA 3rd, Green MR, Tarassoff PG, Brown TD, Casper ES, Storniolo AM, Von Hoff DD. A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol. 1996 Apr;7(4):347-53. link to original article PubMed
- PRODIGE 65: https://clinicaltrials.gov/ct2/show/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 |
Hurwitz et al. 2018 (JANUS 2) | 2014-2016 | Phase 3 (C) | Capecitabine & Ruxolitinib | Did not meet primary endpoint of OS |
Note: the same publication reports on both of these studies.
References
- JANUS 1: Hurwitz H, Van Cutsem E, Bendell J, Hidalgo M, Li CP, Salvo MG, Macarulla T, Sahai V, Sama A, Greeno E, Yu KH, Verslype C, Dawkins F, Walker C, Clark J, O'Reilly EM. Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies. Invest New Drugs. 2018 Aug;36(4):683-695. Epub 2018 Mar 6. link to original article link to PMC article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT02117479
- JANUS 2: Hurwitz H, Van Cutsem E, Bendell J, Hidalgo M, Li CP, Salvo MG, Macarulla T, Sahai V, Sama A, Greeno E, Yu KH, Verslype C, Dawkins F, Walker C, Clark J, O'Reilly EM. Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies. Invest New Drugs. 2018 Aug;36(4):683-695. Epub 2018 Mar 6. link to original article link to PMC article contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT02119663
Sotorasib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Strickler et al. 2022 (CodeBreaK100) | 2019-2021 | Phase 1/2 |
Biomarker eligibility criteria
- KRAS p.G12C mutation
References
- CodeBreaK100: 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 contains dosing details in manuscript PubMed https://clinicaltrials.gov/ct2/show/NCT03600883