Pancreatic cancer
Section editor | |
---|---|
Neeta K. Venepalli, MD, MBA Chicago, IL |
49 regimens on this page
82 variants on this page
|
Guidelines
ASCO
- 2017: Potentially curable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline update PubMed
- 2016: Metastatic pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline
- 2016: Locally advanced, unresectable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline PubMed
ESMO
- 2015: Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2015) PubMed
NCCN
Adjuvant therapy
Capecitabine & Gemcitabine
back to top |
GemCap: Gemcitabine & Capecitabine
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Neoptolemos et al. 2017 (ESPAC-4) | Phase III | Gemcitabine | Seems to have superior OS |
Treatment starts within 12 weeks of surgery.
Chemotherapy
- Capecitabine (Xeloda) 1660 mg/m2/day PO on days 1 to 21 (frequency of dosing not specified)
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per week on weeks 1 to 3
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 protocol PubMed
Fluorouracil & Leucovorin
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Neoptolemos et al. 2001 (ESPAC-1) | Phase III | 5-FU & RT 5-FU & RT, then 5-FU & Leucovorin |
Seems to have superior OS (*) |
Observation | Superior OS (*) | ||
Neoptolemos et al. 2010 (ESPAC-3) | Phase III | Gemcitabine | Seems not superior |
Note: efficacy for ESPAC-1 is based on the 2004 update.
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
- 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 verified protocol PubMed
- 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 verified protocol PubMed
Fluorouracil, then Fluorouracil & RT
back to top |
RT: Radiation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Neoptolemos et al. 2001 (ESPAC-1) | Phase III | 5-FU & Leucovorin Observation |
Seems to have inferior OS (*) |
5-FU & RT, then 5-FU & Leucovorin | Not reported | ||
Regine et al. 2008 | Phase III | Gemcitabine, then Fluorouracil & RT, then Gemcitabine | Seems not superior |
Note: efficacy for ESPAC-1 is based on the 2004 update.
Chemotherapy portion
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion on days 1 to 21
21-day course, followed in 1 to 2 weeks by:
Chemoradiotherapy portion
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion throughout radiation therapy
- Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, 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
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion on days 1 to 28
6-week cycle for 2 cycles
References
- 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 verified protocol PubMed
- 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 verified protocol PubMed
Gemcitabine monotherapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Oettle et al. 2007 (CONKO-001) | Phase III | Observation | Seems to have superior OS |
Neoptolemos et al. 2010 (ESPAC-3) | Phase III | Fluorouracil & Leucovorin | Seems not superior |
Uesaka et al. 2016 (JASPAC 01) | Phase III (C) | S-1 | Inferior OS |
Neoptolemos et al. 2017 (ESPAC-4) | Phase III | Capecitabine & Gemcitabine | Seems to have inferior OS |
Treatment starts day 10 to 42 after surgery or after wound is healed.
Note: efficacy for CONKO-001 is based on the 2013 update.
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
- 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 verified protocol PubMed
- 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
- 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 verified protocol PubMed
- 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 verified protocol PubMed
- 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 protocol PubMed
Gemcitabine, then Fluorouracil & RT, then Gemcitabine
back to top |
RT: Radiation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Regine et al. 2008 | Phase III | Fluorouracil & RT | Seems not superior |
Chemotherapy portion, 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:
Chemoradiotherapy portion
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion throughout radiation therapy
- Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, 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 portion, part 2
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 3 cycles
References
- 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 verified protocol PubMed
Observation
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Neoptolemos et al. 2001 (ESPAC-1) | Phase III (C) | 5-FU & Leucovorin | Inferior OS |
5-FU & RT 5-FU & RT, then 5-FU & Leucovorin |
Seems to have superior OS | ||
Oettle et al. 2007 (CONKO-001) | Phase III (C) | Gemcitabine | Seems to have inferior OS |
No active antineoplastic treatment. Efficacy for ESPAC-1 is based on the 2004 update and efficacy for CONKO-001 is based on 2013 update.
References
- 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 verified protocol PubMed
- 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 verified protocol PubMed
- 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
S-1 monotherapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Uesaka et al. 2016 (JASPAC 01) | Phase III (E) | Gemcitabine | Superior OS |
Treatment starts day 10 to 42 after surgery or after wound is healed.
Chemotherapy
- Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m2: 40 mg PO BID on days 1 to 28
- BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO BID on days 1 to 28
- BSA 1.5 m2 or more: 60 mg PO BID on days 1 to 28
42-day cycle for up to 4 cycles
References
- 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 verified protocol PubMed
Induction therapy for locally advanced disease, potentially resectable
Docetaxel, Gemcitabine, RT
back to top |
RT: Radiation Therapy
Regimen
Study | Evidence |
---|---|
Pipas et al. 2005 | Phase II |
Chemotherapy
- Docetaxel (Taxotere) 65 mg/m2 IV over 60 minutes once per day on days 1, 15, 29
- Gemcitabine (Gemzar) 4000 mg/m2 IV over 30 minutes once per day on days 1, 15, 29
6-week course, followed immediately (day 43) by:
Chemoradiation
- Gemcitabine (Gemzar) 50 mg/m2 IV over 30 minutes twice per week for 12 doses
- Given Monday/Thursday or Tuesday/Friday. Infusion completed ½ to 2 hours prior to RT.
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, 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.
Supportive medications
- GI prophylaxis with a proton pump inhibitor during chemoradiotherapy
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 verified protocol PubMed
Gemcitabine & RT
back to top |
RT: Radiation Therapy
Regimen 1
Study | Evidence |
---|---|
Takahashi et al. 2013 | Phase II |
Chemoradiotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
- Concurrent radiation therapy, 2 Gy per fraction, 5 days per week, 25 fractions, total dose of 50 Gy over 5 weeks.
28-day cycle for 3 cycles
Restaging is performed 8 weeks after radiation complete (2 weeks after chemotherapy complete). Resection immediately thereafter, if feasible.
Regimen 2
Study | Evidence |
---|---|
Landry et al. 2010 | Phase II |
Chemoradiotherapy
- Gemcitabine (Gemzar) 500 mg/m2 IV over 50 minutes once per week for 6 weeks
- 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
Restaging after radiation complete. 4 to 6 week break, followed by surgery, followed by 4 to 8 week break. Then adjuvant chemotherapy:
Adjuvant chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 100 minutes once per day on days 1 & 8
21-day cycle for 5 cycles
References
- 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 verified protocol 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 verified protocol PubMed
Gemcitabine, Cetuximab, RT
back to top |
RT: Radiation Therapy
Regimen
Study | Evidence |
---|---|
Pipas et al. 2012 | Phase II |
Chemoradiotherapy
- Cetuximab (Erbitux) as follows:
- 6 to 8 days prior radiation: 400 mg/m2 IV over 2 hours once
- During radiation: 250 mg/m2 over 60 minutes once per week for 6 doses
- Gemcitabine (Gemzar) 50 mg/m2 IV over 30 minutes twice per week for 12 doses
- Given Monday/Thursday or Tuesday/Friday. Infusion completed ½ to 2 hours prior to RT.
- 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. All fields were treated daily at five fractions per week.
Supportive medications
- 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 ∼6to 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 verified protocol link to PMC article PubMed
mFOLFIRINOX, Gemcitabine, RT
back to top |
mFOLFIRINOX, Gemcitabine, RT: modified FOLinic acid, Fluorouracil, IRINotecan, OXaliplatin, Gemcitabine, Radiation Therapy
Variant #1
Study | Evidence |
---|---|
Blazer et al. 2015 | Retrospective |
Chemotherapy, mFOLFIRINOX portion
- Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion for 46 h on days 1 to 3
- 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 medications
- 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:
Chemoradiotherapy
- Gemcitabine (Gemzar) 1000 mg/m2/week concurrent with radiation
- Radiation was 36 Gy in 15 daily fractions
Variant #2
Study | Evidence |
---|---|
Hosein et al. 2012 | Retrospective |
Chemotherapy, mFOLFIRINOX portion
- Folinic acid (Leucovorin) 400 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 2400 mg/m2 IV continuous infusion for 46 hours on days 1 to 3
- Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycles. Protocol followed "per ACCORD-11 trial"
Treatment stopped at maximum response or tolerability. Resectable patients by imaging criteria were offered surgery, followed by postoperative chemoradiotherapy. Unresectable patients were offered chemoradiotherapy, followed by surgery (if they became resectable):
Chemoradiotherapy
- Gemcitabine (Gemzar) 600 mg/m2/week
- Radiation at 50.4 Gy in 28 fractions.
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
back to top |
Regimen
Study | Evidence |
---|---|
Cartwright et al. 2002 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1 to 14
21-day cycle for up to 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 verified protocol PubMed
Erlotinib & Gemcitabine
back to top |
Variant #1, Gem 3 out of 4 weeks x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hammel et al. 2016 (GERCOR LAP07) | Phase III | See link | See link |
Chemotherapy
- Erlotinib (Tarceva) 100 mg PO once per day
- 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
- Patients without progression: Erlotinib & Gemcitabine x 2 more cycles (6 total) versus Capecitabine, Erlotinib, RT
Variant #2, Gem 3 out of 4 weeks x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hammel et al. 2016 (GERCOR LAP07) | Phase III | See link | See link |
Note: it is not clear from the protocol whether erlotinib is continued beyond the end of chemotherapy.
Chemotherapy
- Erlotinib (Tarceva) as follows:
- Cycles 1 to 4: 100 mg PO once per day
- Cycles 5 & 6: 150 mg PO once per day
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 6 cycles
Variant #3, 8-week lead-in
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Moore et al. 2007 | Phase III (E) | Gemcitabine | Seems to have superior OS |
Note: although this is technically a superior arm, the effect size is considered to be not clinically meaningful.
Initial chemotherapy
- Erlotinib (Tarceva) 100 or 150 mg (100 mg dose recommended) PO once per day
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
8-week course, followed by:
Maintenance chemotherapy
- Erlotinib (Tarceva) 100 or 150 mg (100 mg dose recommended) PO once per day
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
References
- 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 verified protocol PubMed
- 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; LAP07 Trial Group. 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 verified protocol PubMed
Fluorouracil & RT
back to top |
RT: Radiation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Herman et al. 2013 | Phase III (C) | Fluorouracil & RT with TNFerade | Seems not superior |
Chemoradiotherapy
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion once per day on radiation days (total dose per week: 1000 mg/m2)
- Concurrent radiation therapy, 50.4 Gy total: 1.80 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy, followed by 1.80 Gy x 3 fractions boost to the tumor bed.
One course
Subsequent treatment
- Gemcitabine or Erlotinib & Gemcitabine maintenance
References
- 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 verified protocol link to PMC article PubMed
Gemcitabine monotherapy
back to top |
Variant #1, 3 out of 4 weeks x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hammel et al. 2016 (GERCOR LAP07) | Phase III | 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
- Patients without progression: Gemcitabine x 2 more cycles (6 total) versus Capecitabine & RT
Variant #2, 3 out of 4 weeks x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hammel et al. 2016 (GERCOR LAP07) | Phase III | 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
Variant #3, 8-week lead-in
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Louvet et al. 2005 | Phase III | GemOx | Seems to have inferior PFS |
Loehrer et al. 2011 | Phase III | Gemcitabine & RT | Seems to have inferior OS |
Chemotherapy
- Gemcitabine (Gemzar) as follows:
- First 8 weeks: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
- Subsequent 4-week cycles: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
Continued for at least 3 months
Per Louvet et al. 2005, subsequent chemoradiotherapy 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 verified protocol PubMed
- 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 verified protocol link to PMC article PubMed
- 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; LAP07 Trial Group. 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 verified protocol PubMed
Gemcitabine & RT
back to top |
RT: Radiation Therapy
Variant #1 (600 mg/m2)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Cardenes et al. 2011 | Phase II | ||
Loehrer et al. 2011 | Phase III | Gemcitabine | Seems to have superior OS |
Chemoradiotherapy
- Gemcitabine (Gemzar) 600 mg/m2 IV over 30 to 60 minutes once per week during radiation
- Concurrent radiation therapy, 1.8 Gy per fraction, 5 days per week, 28 fractions, total dose of 50.4 Gy over 5.5 weeks.
One course, followed in 4 weeks by:
Maintenance chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per week, 3 out of 4 weeks
28-day cycle for 5 cycles or until disease progression
Variant #2 (400 mg/m2)
Study | Evidence |
---|---|
Epelbaum et al. 2002 | Phase II |
Chemotherapy
- Gemcitabine (Gemzar) 1000mg/m2 IV over 30 minutes once per week for 7 weeks
Radiation planning during this phase, followed by:
Chemoradiotherapy
- Gemcitabine (Gemzar) 400 mg/m2 IV over 30 minutes once per week (days 1, 8, 15)
- Concurrent radiation therapy, 5 days per week, 28 fractions, total dose of 50.4 Gy over 5.5 weeks
28 day cycle for 2 cycles (completion of radiation), followed by:
Maintenance chemotherapy
- Gemcitabine (Gemzar) 1000mg/m2 IV over 30 minutes once per week, 3 out of 4 weeks
28-day cycles until disease progression
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 verified protocol PubMed
- Cardenes HR, Moore AM, Johnson CS, Yu M, Helft P, Chiorean EG, Vinson J, Howard TJ, Stephens AW, Tai DF, Loehrer PJ Sr. 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
- 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. link to original article contains verified protocol link to PMC article PubMed
GemOx
back to top |
GemOx: Gemcitabine, Oxaliplatin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Louvet et al. 2005 | Phase III | Gemcitabine | Seems to have superior PFS |
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 3 months
Subsequent chemoradiotherapy 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 verified protocol PubMed
Metastatic disease, first-line
Capecitabine monotherapy
back to top |
Regimen
Study | Evidence |
---|---|
Cartwright et al. 2002 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1 to 14
21-day cycle for up to 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 verified protocol PubMed
Capecitabine & Gemcitabine
back to top |
GemCap/GEM-CAP: Gemcitabine & Capecitabine
Variant #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Lee et al. 2017 | Phase III | Gemcitabine | Might have superior OS |
Note: this is essentially identical to the maintenance phase of Cunningham et al. 2009, below.
Chemotherapy
- Capecitabine (Xeloda) 1660 mg/m2/day on days 1 to 21 (frequency of dosing not specified)
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Variant #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Cunningham et al. 2009 | Phase III | Gemcitabine | Superior PFS |
Initial chemotherapy
- Capecitabine (Xeloda) 830 mg/m2 PO BID on days 1 to 21, 29 to 49
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
8-week course, followed by:
Maintenance chemotherapy
- Capecitabine (Xeloda) 830 mg/m2 PO BID 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
Variant #3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Herrmann et al. 2007 (SAKK 44/00-CECOG/PAN.1.3.001) | Phase III | Gemcitabine | Seems not superior |
Chemotherapy
- Capecitabine (Xeloda) 650 mg/m2 PO BID 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 24 weeks
References
- 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 verified protocol PubMed
- 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 verified protocol PubMed
- 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 verified protocol PubMed
- 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. contains verified protocol link to PMC article PubMed
Cisplatin & Gemcitabine
back to top |
Variant #1, weekly dosing
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Colucci et al. 2010 (GIP-1) | Phase III (E) | Gemcitabine | Seems not superior |
Note that cisplatin is not given on day 22 of the first 8 weeks; otherwise, the schedule is identical to the schedule for gemcitabine.
Chemotherapy
- Cisplatin (Platinol) as follows, given 60 minutes prior to gemcitabine:
- First 8 weeks: 25 mg/m2 IV once per day on days 1, 8, 15, 29, 36, 43
- Subsequent cycles: 25 mg/m2 IV once per day on days 1, 8, 15
- Gemcitabine (Gemzar) as follows:
- First 8 weeks: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
- Subsequent cycles: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Variant #2, bi-weekly dosing
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Heinemann et al. 2006 | Phase III (E) | Gemcitabine | Might have superior PFS |
Cascinu et al. 2008 (GISCAD) | Randomized Phase II (C) | Cisplatin, Gemcitabine, Cetuximab | Seems not superior |
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
- 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 verified regimen PubMed
- 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 (GISCAD). 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 protocol PubMed
- 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; Gruppo Oncologico Italia Meridionale (GOIM).; Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente (GISCAD).; Gruppo Oncologico Italiano di Ricerca Clinica (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 verified protocol PubMed
Erlotinib & Gemcitabine
back to top |
Variant #1, no gemcitabine lead-in
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kordes et al. 2015 | Randomized Phase II (C) | Erlotinib, Gemcitabine, Metformin | Seems not superior |
Chemotherapy
- Erlotinib (Tarceva) 100 mg PO once per day
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Variant #2, gemcitabine lead-in, erlotinib 100 mg/d
FDA-recommended dose |
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Moore et al. 2007 (NCIC CTG PA.3) | Phase III (E) | Gemcitabine | Seems to have superior OS |
Chemotherapy
- Erlotinib (Tarceva) 100 mg PO once per day
- 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
One 8-week cycle, then 28-day cycles
Variant #3, gemcitabine lead-in, erlotinib 150 mg/d
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Moore et al. 2007 (NCIC CTG PA.3) | Phase III (E) | Gemcitabine | Not reported |
Note: due to low accrual, the efficacy of this arm could not be determined.
Chemotherapy
- Erlotinib (Tarceva) 150 mg PO once per day
- 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
One 8-week 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 verified protocol PubMed
- 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 protocol PubMed
Fluorouracil monotherapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Burris et al. 1997 | Phase III | Gemcitabine | Inferior OS |
Inferior to gemcitabine. Here for historical reference purposes, only.
References
- Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. link to original article contains verified protocol PubMed
FOLFIRINOX
back to top |
FOLFIRINOX: FOLinic acid, Fluorouracil, IRINotecan, OXaliplatin
Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Conroy et al. 2011 (PRODIGE 4/ACCORD 11) | Phase III | Gemcitabine | Superior OS | 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, then 1200 mg/m2/day IV continuous 46-hour infusion on days 1 to 2; given last (total dose per cycle: 2400 mg/m2)
- Irinotecan (Camptosar) 180 mg/m2 IV over 90 minutes once on day 1; given third together 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
- 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 verified protocol PubMed
- QoL 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
Gemcitabine monotherapy
back to top |
Variant #1, 8-week lead-in
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Burris et al. 1997 | Phase III (E) | 5-FU | Superior OS |
Louvet et al. 2005 | Phase III (C) | GemOx | Seems to have inferior PFS |
Reni et al. 2005 | Phase III (C) | PEFG | Seems to have inferior PFS |
Moore et al. 2007 | Phase III (C) | Erlotinib & Gemcitabine | Seems to have inferior OS |
Herrmann et al. 2007 (SAKK 44/00-CECOG/PAN.1.3.001) | Phase III (C) | GemCap | Seems not superior |
Poplin et al. 2009 (ECOG E6201) | Phase III (C) | GEM FDR | Might have inferior OS |
GEMOX | Seems not superior | ||
Cunningham et al. 2009 | Phase III (C) | GEM-CAP | Inferior PFS |
Colucci et al. 2010 (GIP-1) | Phase III (C) | Cisplatin & Gemcitabine | Seems not superior |
Philip et al. 2010 (SWOG S0205) | Phase III (C) | Gemcitabine & Cetuximab | Seems not superior |
Conroy et al. 2011 (PRODIGE 4/ACCORD 11) | Phase III (C) | FOLFIRINOX | Inferior OS |
Von Hoff et al. 2013 (MPACT) | Phase III (C) | Gemcitabine & nab-Paclitaxel | Inferior OS |
Middleton et al. 2017 (ViP) | Randomized Phase II (C) | Gemcitabine & Vandetanib | Seems not superior |
Chemotherapy
- Gemcitabine (Gemzar) as follows:
- First 8 weeks: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
- Subsequent cycles: 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
28-day cycles
Variant #2, 4 week cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Heinemann et al. 2006 | Phase III | Cisplatin & Gemcitabine | Might have inferior PFS |
Kindler et al. 2011 | Phase III | Gemcitabine & Axitinib | Seems not superior |
Ueno et al. 2013 (GEST) | Phase III (C) | S-1 | Non-inferior OS |
Gemcitabine & S-1 | Seems not superior | ||
Fuchs et al. 2015 (GAMMA) | Randomized Phase Ib/II | Gemcitabine & Ganitumab | Seems not superior |
Catenacci et al. 2015 | Randomized Phase Ib/II | Gemcitabine & Vismodegib | Seems not superior |
Lee et al. 2017 | Phase III | GemCap | Might have inferior OS |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Variant #3, 3 week cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hong et al. 2013 | Randomized Phase II | Gemcitabine & Simvastatin | Seems not superior |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
21-day cycles
Variant #4, fixed-dose rate (FDR)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Poplin et al. 2009 (ECOG E6201) | Phase III | Gemcitabine | Might have superior OS |
GEMOX | Not reported |
Chemotherapy
- Gemcitabine (Gemzar) 1500 mg/m2 IV over 150 minutes (10 mg/m2/min) once per day on days 1, 8, 15
28-day cycles
References
- Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. link to original article contains verified protocol 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 verified protocol PubMed
- Reni M, Cordio S, Milandri C, Passoni P, Bonetto E, Oliani C, Luppi G, Nicoletti R, Galli L, Bordonaro R, Passardi A, Zerbi A, Balzano G, Aldrighetti L, Staudacher C, Villa E, Di Carlo V. Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial. Lancet Oncol. 2005 Jun;6(6):369-76. link to original article contains protocol 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 verified regimen PubMed
- 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 verified protocol PubMed
- 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 verified protocol PubMed
- 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 verified protocol 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 verified protocol link to PMC article PubMed
- 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 verified protocol PubMed
- 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; Gruppo Oncologico Italia Meridionale (GOIM).; Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente (GISCAD).; Gruppo Oncologico Italiano di Ricerca Clinica (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 protocol PubMed
- 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 verified protocol link to PMC article PubMed
- 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 verified protocol PubMed
- 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 verified protocol PubMed
- QoL 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
- 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 verified protocol PubMed
- 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 verified protocol link to PMC article PubMed
- Hong JY, Nam EM, Lee J, Park JO, Lee SC, Song SY, Choi SH, Heo JS, Park SH, Lim HY, Kang WK, Park YS. Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients. Cancer Chemother Pharmacol. 2014 Jan;73(1):125-30. Epub 2013 Oct 27. link to original article contains verified protocol PubMed
- 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. contains verified protocol link to PMC article PubMed
- 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 protocol in supplement link to PMC article PubMed
- 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. contains verified protocol 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 protocol PubMed
GemOx
back to top |
GemOx: Gemcitabine, Oxaliplatin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Louvet et al. 2005 | Phase III | Gemcitabine | Seems to have superior PFS |
Poplin et al. 2009 (E6201) | Phase III | Gemcitabine | Seems not superior |
Gemcitabine, FDR | Not reported |
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 verified protocol PubMed
- 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 verified protocol link to PMC article PubMed
Gemcitabine & nab-Paclitaxel
back to top |
Variant #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Von Hoff et al. 2013 (MPACT) | Phase III | Gemcitabine | Superior OS |
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 followed by 28-day cycles until disease progression or intolerance
Variant #2
Study | Evidence |
---|---|
Von Hoff et al. 2011 | Phase II |
Note: The abstract and body of Von Hoff et al. 2011 contradicted each other about which drug is given first in this regimen.
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 or 125 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- 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 verified protocol link to PMC article PubMed
- 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 verified protocol link to PMC article PubMed
GTX
back to top |
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 BID. The 2009 ASCO abstract by Fine also lists this 750 mg/m2 PO BID (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 BID 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 protocol 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 verified protocol--with error as noted above link to PMC article PubMed
S-1 monotherapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ueno et al. 2013 (GEST) | Phase III (E) | Gemcitabine | Non-inferior OS |
Gemcitabine & S-1 | Not reported |
Chemotherapy
- Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m2: 40 mg PO BID on days 1 to 28
- BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO BID on days 1 to 28
- BSA 1.5 m2 or more: 60 mg PO BID 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 verified protocol PubMed
Metastatic disease, refractory
Best supportive care
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pelzer et al. 2011 (CONKO) | Phase III | OFF | Inferior OS |
Best supportive care. Placed here because one or more randomized clinical trials included a best supportive care arm in this disease context.
References
- 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 verified protocol--with error as noted above PubMed
Capecitabine & Erlotinib
back to top |
Regimen
Study | Evidence |
---|---|
Kulke et al. 2007 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 (rounded to the nearest 150 mg tablet) PO BID on days 1 to 14
- 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 verified protocol PubMed
CapeOx
back to top |
CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda (Capecitabine), OXaliplatin
Regimen
Study | Evidence |
---|---|
Xiong et al. 2008 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) as follows:
- Age less than 65 years old and ECOG performance status less than 2: 1000 mg/m2 PO BID 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 BID on days 1 to 14
- Oxaliplatin (Eloxatin) as follows:
- 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 verified protocol PubMed
Fluorouracil, Folinic acid, nanoliposomal Irinotecan
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Wang-Gillam et al. 2015 (NAPOLI-01) | Phase III | Fluorouracil & Folinic acid | Seems to have superior OS |
Irinotecan, nanoliposomal | Not reported |
Chemotherapy
- Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1 after folinic acid
- Folinic acid (Leucovorin) 400 mg/m2 IV over 30 minutes once on day 1, given prior to fluorouracil
- 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-01), 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
- 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 verified protocol PubMed
FOLFIRI
back to top |
FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan
Variant #1
Study | Evidence |
---|---|
Zaniboni et al. 2012 (GISCAD) | Phase II |
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, and 600 mg/m2 IV continuous infusion over 22 hours on days 1 & 2 (total dose per cycle: 2000 mg/m2)
- Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
14-day cycles
Variant #2, modified FOLFIRI.3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Yoo et al. 2009 | Randomized Phase II | mFOLFOX | Seems not superior |
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
- Irinotecan (Camptosar) 70 mg/m2 IV once per day on days 1 & 3
14-day cycles
References
- 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 protocol link to PMC article PubMed
- 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 protocol PubMed
FOLFOX
back to top |
FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Yoo et al. 2009 | Randomized Phase II | mFOLFIRI.3 | Seems not superior |
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
- 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 protocol link to PMC article PubMed
OFF
back to top |
OFF: Oxaliplatin, Fluorouracil, Folinic acid
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pelzer et al. 2011 (CONKO) | Phase III | Best supportive care | Superior OS |
Oettle et al. 2014 (CONKO-003) | Phase III | Fluorouracil & Folinic acid | Superior OS |
Note: The treatment section of Pelzer et al. 2011 incorrectly lists the oxaliplatin dose as "0.85 g/m2," or 850 mg/m2.
Chemotherapy
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 to 4 hours once per day on days 8 & 22, given first
- Fluorouracil (5-FU) 2000 mg/m2 IV continuous 24-hour infusion on days 1, 8, 15, 22, started after folinic acid bolus
- Folinic acid (Leucovorin) 200 mg/m2 IV bolus once per day on days 1, 8, 15, 22, given prior to fluorouracil
42-day cycles
References
- 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 verified protocol--with error as noted above PubMed
- 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 verified protocol PubMed
Olaparib monotherapy
back to top |
Regimen
Study | Evidence |
---|---|
Kaufman et al. 2014 | Phase II |
Patients had germline BRCA1/2 mutations and had previously received gemcitabine.
Chemotherapy
- Olaparib (Lynparza) 400 mg PO BID
Continued until progression
References
- Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. link to original article contains verified protocol PubMed
Paclitaxel, nanoparticle albumin-bound monotherapy
back to top |
Regimen
Study | Evidence |
---|---|
Hosein et al. 2013 | Phase II |
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 protocol PubMed