Skip to main content

Advertisement

SpringerLink
Log in

The Role of the FOLFIRINOX Regimen for Advanced Pancreatic Cancer

  • Gastrointestinal Cancers (BG Czito, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

In 2010, the FOLFIRINOX regimen (bolus and infusional 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) emerged as a new option in patients with metastatic pancreatic cancer and a good performance status. However, at that time, some doubts were raised regarding safety issues. Similarly, no data on FOLFIRINOX were published in patients with unresectable/locally advanced or borderline resectable pancreatic cancer. This article presents the available experience with FOLFIRINOX outside clinical trials in metastatic and locally advanced pancreatic cancer patients. The safety of the regimen in patients with biliary stents and in previously treated patients is also described. FOLFIRINOX usage in clinical practice, including modification of the regimen (omission of bolus 5-fluorouracil; FOLFOXIRI regimen), is also presented. These data suggest that a phase III randomized study is warranted to further explore the role of FOLFIRINOX in locally advanced pancreatic cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as • Of importance •• Of major importance

  1. GLOBOCAN. Cancer incidence, mortality and prevalence worldwide in 2008. http://globocan.iarc.fr/factsheet.asp (2008).

  2. Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62:10–29.

    Article  PubMed  Google Scholar 

  3. Sant M, Allemani C, Santaquilani M, et al. EUROCARE Working Group. EUROCARE-4. Survival of cancer patients diagnosed in 1995–1999. Results and commentary. Eur J Cancer. 2009;45:931–91.

    Article  PubMed  Google Scholar 

  4. Niederhuber JE, Brennan MF, Menck HR. The National Cancer Data Base report on pancreatic cancer. Cancer. 1995;76:1671–7.

    Article  PubMed  CAS  Google Scholar 

  5. Lefebvre AC, Maurel J, Boutreux S, et al. Pancreatic cancer: incidence, treatment and survival trends – 1175 cases in Calvados (France) from 1978 to 2002. Gastroenterol Clin Biol. 2009;33:1045–51.

    Article  PubMed  Google Scholar 

  6. Burris 3rd AH, Moore MJ, Andersen J, 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;15:2403–13.

    PubMed  CAS  Google Scholar 

  7. Conroy T, Mitry E. Chimiothérapie de l’adénocarcinome du pancréas métastatique: défis et espoirs. Bull Cancer. 2011;98:1438–46.

    Google Scholar 

  8. •• Cunningham D, Chau I, Stocken DD, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009;27:5513–8. The gemcitabine–capecitabine combination resulted in higher response rate and improved PFS over gemcitabine; a trend toward better overall survival was observed.

    Article  PubMed  CAS  Google Scholar 

  9. Moore MJ, Goldstein D, Hamm J, 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;25:1960–6.

    Article  PubMed  CAS  Google Scholar 

  10. Ychou M, Conroy T, Seitz JF, et al. An open label phase I study assessing the feasibility of the triple combination: oxaliplatin plus irinotecan plus leucovorin/5-flourouracil every 2 weeks in patients with advanced solid tumors. Ann Oncol. 2003;14:481–9.

    Article  PubMed  CAS  Google Scholar 

  11. Zeghari-Squalli N, Raymond E, Cvitkovic E, Goldwasser F. Cellular pharmacology of the combination of the DNA topoisomerase I inhibitor SN-38 and the diaminocyclohexane platinum derivative oxaliplatin. Clin Cancer Res. 1999;5:1189–96.

    PubMed  CAS  Google Scholar 

  12. Ychou M, Viret F, Kramar A, et al. Tritherapy with fluorouracil/leucovorin, irinotecan and oxaliplatin (FOLFIRINOX): a phase II study in colorectal cancer patients with non-resectable liver metastases. Cancer Chemother Pharmacol. 2008;62:195–201.

    Article  PubMed  CAS  Google Scholar 

  13. Conroy T, Paillot B, François E, et al. Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer – a Groupe Tumeurs Digestives of the Fédération Nationale des Centres de Lutte Contre le Cancer study. J Clin Oncol. 2005;23:1228–36.

    Article  PubMed  CAS  Google Scholar 

  14. Herrmann R, Bodoky G, Ruhstaller T, et al. 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;25:2212–7.

    Article  PubMed  CAS  Google Scholar 

  15. Heinemann V, Boeck S, Hinke A, Labianca R, Louvet C. Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer. 2008;8:82.

    Article  PubMed  Google Scholar 

  16. Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998;16:139–44.

    PubMed  CAS  Google Scholar 

  17. •• Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine in patients with metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25. This pivotal randomized phase III study showed that FOLFIRINOX is superior to single-agent gemcitabine in response rate, PFS, and overall survival without a deleterious effect on quality of life.

    Article  PubMed  CAS  Google Scholar 

  18. Louvet C, Labianca R, Hammel P, et al. 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;23:3509–16.

    Article  PubMed  CAS  Google Scholar 

  19. • Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, et al. 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;31:23–9. This article presents detailed results of quality-of-life measurements in the pivotal PRODIGE 4/ACCORD 11 trial. Physical functioning, constipation, and dyspnea were dependent significant prognostic factors for survival with clinical variables.

    Article  PubMed  CAS  Google Scholar 

  20. Bendell JC, Britton S, Green MR, et al. Immediate impact of the FOLFIRINOX phase III data reported at the 2010 ASCO Annual Meeting on prescribing plans of American oncology physicians for patients with metastatic pancreas cancer. J Clin Oncol. 2011; 29 (Suppl, Abstr 286).

  21. Attard CL, Brown S, Alloul K, et al. Cost-effectiveness of FOLFIRINOX for first-line treatment of metastatic pancreatic cancer. J Clin Oncol. 2012; 30 (suppl; abstr 199).

    Google Scholar 

  22. Ko AH. FOLFIRINOX: a small step or a great leap forward? J Clin Oncol. 2011;29:3727–9.

    Article  PubMed  Google Scholar 

  23. Peddi PF, Lubner S, McWilliams R, et al. Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. JOP. 2012;13:497–501.

    PubMed  Google Scholar 

  24. Vaccaro V, Bria E, Sperduti I, et al. First-line treatment with FOLFIRINOX in advanced, inoperable pancreatic cancer (APDAC) patients (pts): supportive measures optimization for a safe administration in routine clinical practice. Ann Oncol. 2012;23 Suppl 9:ix240. Abstr 721P.

    Google Scholar 

  25. Goncalves PH, Ruch JM, Byer J, et al. Multi-institutional experience using 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in patients with pancreatic cancer (PCA). J Clin Oncol. 2012; 30 (Suppl; Abstr e14519).

  26. Faris JE, Hong TS, McDermott S et al. FOLFIRINOX in locally advanced and metastatic pancreatic cancer. J Clin Oncol. 2012; 30 (Suppl 4; Abstr 313).

  27. Gunturu KS, Thumar JR, Hochster HS, et al. Single institution experience with FOLFIRINOX in advanced pancreatic cancer (PC). J Clin Oncol. 2012; 30 (Suppl 4; Abstr 330).

  28. • Hosein PJ, Macintyre J, Kawamura C, et al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12:199. This is the first published series of patients treated with FOLFIRINOX with unresectable or borderline resectable LAPC. Treatment with FOLFIRINOX in this setting is feasible and achieves some R0 resections.

    Article  PubMed  CAS  Google Scholar 

  29. Lowery MA, Yu KH, Adel NG, et al. Activity of front-line FOLFIRINOX (FFX) in stage III/IV pancreatic adenocarcinoma (PC) at Memorial Sloan-Kettering Cancer Center (MSKCC). J Clin Oncol. 2012;30:252s. Suppl; Abstr 4057.

    Google Scholar 

  30. Ko AH, LoConte NK, Emily Kantoff E, et al. A phase Ib trial of FOLFIRINOX plus saridegib, an oral hedgehog (Hh) inhibitor, in pts with advanced pancreatic cancer (PDAC). J Clin Oncol. 2012; 30 (Suppl; Abstr 3105).

  31. Mahaseth H, Kauh JS, Edith Brutcher E, et al. safety and efficacy of modified FOLFIRINOX in pancreatic cancer: a retrospective experience. J Clin Oncol. 2012; 30 (Suppl; Abstr e14614).

  32. Vasile E, De Lio N, Cappelli C, et al. Neoadjuvant modified FOLFOXIRI in locally advanced pancreatic cancer. Ann Oncol. 2012;23 Suppl 9:ix241. Abstr 726P.

    Google Scholar 

  33. Ginocchi L, Vasile E, Caponi S, et al. Modified FOLFOXIRI in advanced pancreatic cancer. Ann Oncol. 2012;23 Suppl 9:ix238. Abstr 714P.

    Google Scholar 

  34. Assaf E, Verlindhe-Carvalho M, Delbaldo C, et al. 5-Fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma. Oncology. 2011;80:301–6.

    Article  PubMed  CAS  Google Scholar 

  35. Breysacher G, Kaatz O, Lemarignier C, et al. Safety and clinical effectiveness of FOLFIRINOX in metastatic pancreas cancer after first-line therapy. J Clin Oncol. 2010; 28 (Suppl; Abstr 269).

    Google Scholar 

  36. Callery MP, Chang KJ, Fishman EK, et al. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16:1727–33.

    Article  PubMed  Google Scholar 

  37. Huguet F, André T, Hammel P, et al. Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol. 2007;25:326–31.

    Article  PubMed  CAS  Google Scholar 

  38. Kharofa J, Kelly TR, Ritch PS, et al. 5-FU/leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) induction followed by chemoXRT in borderline resectable pancreatic cancer. J Clin Oncol. 2012; 30 (Suppl; Abstr e14613).

  39. Marthey L, Sa-Cunha A, Blanc JF, et al. FOLFIRINOX for locally advanced pancreatic adenocarcinoma. results of an AGEO multicentric prospective study. Ann Oncol. 2012;23 Suppl 9:ix238. Abstr 716P.

    Google Scholar 

Download references

Disclosure

T. Conroy: none; C. Gavoille: none; E. Samalin: none; M. Ychou: none; and M. Ducreux: board membership (Sanofi) and honoraria (Sanofi and Pfizer).

Author information

Authors and Affiliations

  1. EA 4360 and Department of Medical Oncology, Centre Alexis Vautrin, Université de Lorraine, CS 30519, 54519, Vandoeuvre-lès-Nancy Cedex, France

    Thierry Conroy

  2. Department of Medical Oncology, Centre Alexis Vautrin, CS 30519, 54519, Vandoeuvre-lès-Nancy Cedex, France

    Thierry Conroy & Céline Gavoille

  3. Department of Medical Oncology, Centre Val d’Aurelle, 208 rue des apothicaires, 34298, Montpellier Cedex 5, France

    Emmanuelle Samalin & Marc Ychou

  4. Department of Medicine, Institut Gustave Roussy, 114, rue Edouard Vaillant – Couturier, 94805, Villejuif Cedex, France

    Michel Ducreux

Authors
  1. Thierry Conroy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Céline Gavoille
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emmanuelle Samalin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marc Ychou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michel Ducreux
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thierry Conroy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Conroy, T., Gavoille, C., Samalin, E. et al. The Role of the FOLFIRINOX Regimen for Advanced Pancreatic Cancer. Curr Oncol Rep 15, 182–189 (2013). https://doi.org/10.1007/s11912-012-0290-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-012-0290-4

Keywords

Search

Navigation