Medical Oncology

, 33:37 | Cite as

Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience

  • M. Bupathi
  • D. H. Ahn
  • C. Wu
  • K. K. Ciombor
  • J. A. Stephens
  • J. Reardon
  • D. A. Goldstein
  • T. Bekaii-SaabEmail author
Original Paper


Pancreatic adenocarcinoma is the fourth leading cause of cancer death. Recently, MM-398 (nanoliposomal irinotecan) was shown to be associated with significant improvement in outcome measures with acceptable toxicities when combined with 5-fluorouracil (5-FU)/leucovorin (LV) compared to 5-FU/LV alone in patients failing one line of gemcitabine-based therapy. There is a paucity of data evaluating the role of irinotecan in combination with 5FU in advanced pancreas cancer (APC). We performed a retrospective analysis of all patients who received mFOLFIRI (minus bolus 5FU and LV). All patients with metastatic disease who had failed at least one line of gemcitabine-based therapy prior to receiving mFOLFIRI were included in this study. Descriptive statistics were used to assess the continuous variables and adverse events (AEs), and Kaplan–Meier methods were used to calculate the median progression-free survival (PFS) and overall survival (OS). Forty patients were included in this analysis. Patients received 1–5 lines of prior therapy (25 % with more than 3 lines of prior therapy). The mean age at diagnosis was 60, and 98 % had ECOG of 1. The mean CA 19-9 at the start of therapy was 33,169 U/ml. The median PFS was 2.59 months [95 % confidence interval (CI) (1.90, 3.54)], and OS was 4.75 months [95 % CI (3.14, 8.98)]. The most common AEs included fatigue (98 %), neuropathy (83 %), anorexia (68 %), nausea (60 %) and constipation (55 %). Grade 3 toxicities included fatigue (13 %) and rash (3 %). There were no observed grade 4 toxicities. In this single-institution retrospective analysis, mFOLFIRI was found to be both tolerable and relatively effective in a heavily pretreated patient population with APC. Future prospective studies should consider evaluating the role of mFOLFIRI in refractory APC.


Pancreatic Cancer FOLFIRI Gemcitabine Adverse effects Tolerability 




Compliance with ethical standards

Conflict of interest

The authors have declared no conflicts of interest.


  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.CrossRefPubMedGoogle Scholar
  2. 2.
    Rahib L, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21.CrossRefPubMedGoogle Scholar
  3. 3.
    Gall TM, et al. Pancreatic cancer: current management and treatment strategies. Postgrad Med J. 1080;2015(91):601–7.Google Scholar
  4. 4.
    Burris HA 3rd, et al. 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;15(6):2403–13.PubMedGoogle Scholar
  5. 5.
    Di Marco M, et al. State of the art biological therapies in pancreatic cancer. World J Gastrointest Oncol. 2016;8(1):55–66.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Moore MJ, et al. 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;25(15):1960–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Goldstein D, et al. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst. 2015;107(2):dju413.CrossRefPubMedGoogle Scholar
  8. 8.
    Conroy T, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRefPubMedGoogle Scholar
  9. 9.
    Von Hoff DD, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.CrossRefGoogle Scholar
  10. 10.
    Wang-Gillam A, et al. 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;387(10018):545–57CrossRefPubMedGoogle Scholar
  11. 11.
    Pelzer U, et al. 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;47(11):1676–81.CrossRefPubMedGoogle Scholar
  12. 12.
    Gill SEA. PANCREOX: a randomized phase 3 study of 5FU/LV with or without oxaliplatin for second-line advanced pancreatic cancer (APC) in patients (pts) who have received gemcitabine (GEM)-based chemotherapy (CT). J Clin Oncol. 2014;32:5s (suppl; abstr 4022).Google Scholar
  13. 13.
    Institute NC. Common terminology criteria for adverse events v4.0. NCI, NIH, DHHS, NIH publication #09-7473; 2009.Google Scholar
  14. 14.
    Goldstein DA, et al. First- and second-line bevacizumab in addition to chemotherapy for metastatic colorectal cancer: a United States-based cost-effectiveness analysis. J Clin Oncol. 2015;33(10):1112–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Custodio A, et al. Second-line therapy for advanced pancreatic cancer: a review of the literature and future directions. Cancer Treat Rev. 2009;35(8):676–84.CrossRefPubMedGoogle Scholar
  16. 16.
    Yi SY, et al. Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer. Cancer Chemother Pharmacol. 2009;63(6):1141–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Walker EJ, Ko AH. Beyond first-line chemotherapy for advanced pancreatic cancer: An expanding array of therapeutic options? World J Gastroenterol. 2014;20(9):2224–36.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Takahara N, et al. Uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1) polymorphisms are associated with toxicity and efficacy in irinotecan monotherapy for refractory pancreatic cancer. Cancer Chemother Pharmacol. 2013;71(1):85–92.CrossRefPubMedGoogle Scholar
  19. 19.
    Assaf E, et al. 5-Fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma. Oncology. 2011;80(5–6):301–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Cantore M, et al. Combined irinotecan and oxaliplatin in patients with advanced pre-treated pancreatic cancer. Oncology. 2004;67(2):93–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Oh SY, et al. Pilot study of irinotecan/oxalipltin (IROX) combination chemotherapy for patients with gemcitabine- and 5-fluorouracil- refractory pancreatic cancer. Invest New Drugs. 2010;28(3):343–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Yoo C, et al. 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;101(10):1658–63.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gebbia V, et al. Irinotecan plus bolus/infusional 5-fluorouracil and leucovorin in patients with pretreated advanced pancreatic carcinoma: a multicenter experience of the Gruppo Oncologico Italia Meridionale. Am J Clin Oncol. 2010;33(5):461–4.CrossRefPubMedGoogle Scholar
  24. 24.
    Zaniboni A, et al. FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multicenter phase II study. Cancer Chemother Pharmacol. 2012;69(6):1641–5.CrossRefPubMedGoogle Scholar
  25. 25.
    Neuzillet C, et al. FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine and platinum-salts. World J Gastroenterol. 2012;18(33):4533–41.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ulrich-Pur H, et al. Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. Br J Cancer. 2003;88(8):1180–4.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Ko AH, et al. Excess toxicity associated with docetaxel and irinotecan in patients with metastatic, gemcitabine-refractory pancreatic cancer: results of a phase II study. Cancer Invest. 2008;26(1):47–52.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • M. Bupathi
    • 1
  • D. H. Ahn
    • 1
  • C. Wu
    • 1
  • K. K. Ciombor
    • 1
  • J. A. Stephens
    • 2
  • J. Reardon
    • 3
  • D. A. Goldstein
    • 4
    • 5
  • T. Bekaii-Saab
    • 1
    Email author
  1. 1.Department of Medical Oncology, Richard Solove Research Institute and James Cancer HospitalThe Ohio State University Wexner Medical CenterColumbusUSA
  2. 2.Department of Biomedical Informatics, Center for BiostatisticsThe Ohio State UniversityColumbusUSA
  3. 3.Department of Pharmacy, Richard Solove Research Institute and James Cancer HospitalThe Ohio State UniversityColumbusUSA
  4. 4.Winship Cancer InstituteEmory UniversityAtlantaUSA
  5. 5.Davidoff Cancer CenterRabin Medical CenterPetach TikvaIsrael

Personalised recommendations