Current Oncology Reports

, Volume 15, Issue 2, pp 182–189 | Cite as

The Role of the FOLFIRINOX Regimen for Advanced Pancreatic Cancer

  • Thierry Conroy
  • Céline Gavoille
  • Emmanuelle Samalin
  • Marc Ychou
  • Michel Ducreux
Gastrointestinal Cancers (BG Czito, Section Editor)

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.

Keywords

Pancreatic cancer Chemotherapy Oxaliplatin Irinotecan 

Notes

Disclosure

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

References

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

  1. 1.
    GLOBOCAN. Cancer incidence, mortality and prevalence worldwide in 2008. http://globocan.iarc.fr/factsheet.asp (2008).
  2. 2.
    Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62:10–29.PubMedCrossRefGoogle Scholar
  3. 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.PubMedCrossRefGoogle Scholar
  4. 4.
    Niederhuber JE, Brennan MF, Menck HR. The National Cancer Data Base report on pancreatic cancer. Cancer. 1995;76:1671–7.PubMedCrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedGoogle Scholar
  7. 7.
    Conroy T, Mitry E. Chimiothérapie de l’adénocarcinome du pancréas métastatique: défis et espoirs. Bull Cancer. 2011;98:1438–46.Google Scholar
  8. 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 gemcitabinecapecitabine combination resulted in higher response rate and improved PFS over gemcitabine; a trend toward better overall survival was observed.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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).Google Scholar
  21. 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. 22.
    Ko AH. FOLFIRINOX: a small step or a great leap forward? J Clin Oncol. 2011;29:3727–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Peddi PF, Lubner S, McWilliams R, et al. Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. JOP. 2012;13:497–501.PubMedGoogle Scholar
  24. 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. 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).Google Scholar
  26. 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).Google Scholar
  27. 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).Google Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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. 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).Google Scholar
  31. 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).Google Scholar
  32. 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. 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. 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.PubMedCrossRefGoogle Scholar
  35. 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. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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).Google Scholar
  39. 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

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Thierry Conroy
    • 1
    • 2
  • Céline Gavoille
    • 2
  • Emmanuelle Samalin
    • 3
  • Marc Ychou
    • 3
  • Michel Ducreux
    • 4
  1. 1.EA 4360 and Department of Medical Oncology, Centre Alexis VautrinUniversité de LorraineVandoeuvre-lès-Nancy CedexFrance
  2. 2.Department of Medical OncologyCentre Alexis VautrinVandoeuvre-lès-Nancy CedexFrance
  3. 3.Department of Medical OncologyCentre Val d’AurelleMontpellier Cedex 5France
  4. 4.Department of MedicineInstitut Gustave RoussyVillejuif CedexFrance

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