Annals of Surgical Oncology

, Volume 22, Issue 1, pp 295–301

FOLFIRINOX for Locally Advanced Pancreatic Adenocarcinoma: Results of an AGEO Multicenter Prospective Observational Cohort

  • L. Marthey
  • A. Sa-Cunha
  • J. F. Blanc
  • M. Gauthier
  • A. Cueff
  • E. Francois
  • I. Trouilloud
  • D. Malka
  • J. B. Bachet
  • R. Coriat
  • E. Terrebonne
  • C. De La Fouchardière
  • S. Manfredi
  • D. Solub
  • C. Lécaille
  • A. Thirot Bidault
  • F. Carbonnel
  • J. Taieb
Pancreatic Tumors

Abstract

Background

First-line treatment with FOLFIRINOX significantly increases overall survival (OS) in patients with metastatic pancreatic adenocarcinoma (PA) compared with gemcitabine. The aim of this observational cohort was to evaluate the tolerability and efficacy of this regimen in unresectable locally advanced PA (LAPA).

Patients and Methods

From February 2010 to February 2012, all consecutive patients from 11 French centers treated by FOLFIRINOX for a histologically proven LAPA were prospectively enrolled. Unresectability was defined independently by each center’s multidisciplinary staff at diagnosis. Absence of metastatic disease was confirmed by chest-abdomen-pelvis computed tomography scan. FOLFIRINOX was delivered every 2 weeks as previously reported until progressive disease, major toxicity, or consolidation treatment by radiotherapy and/or surgery.

Results

Seventy-seven patients were enrolled. They received a median number of five cycles (1–30). Grade 3–4 toxicities were neutropenia (11 %), nausea (9 %), diarrhea (6 %), fatigue (6 %), and anemia (1 %). Grade 2–3 sensory neuropathy occurred in 25 % of patients. No toxic death was reported and only 6 % of patients had to stop treatment because of toxicity. Disease control rate was 84 with 28 % of objective response (Response Evaluation Criteria in Solid Tumors). Seventy-five percent of patients received a consolidation therapy: 70 % had radiotherapy and 36 % underwent a surgical resection, with a curative intent. Within the whole cohort, 1-year OS rate was 77 % (95 % CI 65–86) and 1-year progression-free survival rate was 59 % (95 % CI 46–70).

Conclusion

First-line FOLFIRINOX for LAPA seems to be effective and have a manageable toxicity profile. These promising results will have to be confirmed in a phase III randomized trial.

References

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Sant M, Allemani C, Santaquilani M, Knijn A, Marchesi F, Capocaccia R; EUROCARE Working Group. EUROCARE-4. Survival of cancer patients diagnosed in 1995–1999: results and commentary. Eur J Cancer. 2009;45:931–991.PubMedCrossRefGoogle Scholar
  3. 3.
    Réseau français des registres du cancer Francim. Evolution de l’incidence et de la mortalité par cancer en France de 1978 à 2000: Institut national de la santé et de la recherche médicale, Inserm, InVS; 2003.Google Scholar
  4. 4.
    Katz M, Wang H, Fleming J, et al. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol. 2009;16:836–87.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine versus observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297:267–277.PubMedCrossRefGoogle Scholar
  6. 6.
    Neoptolemos J, Stocken D, Friess H, et al., for the European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200–10.PubMedCrossRefGoogle Scholar
  7. 7.
    Conroy T, Desseigne F, Ychou M, et al., for the Groupe Tumeurs Digestives of Unicancer and the PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–1825.PubMedCrossRefGoogle Scholar
  8. 8.
    Cancer Therapy Evaluation Program. Common terminology criteria for adverse events, version 3.0. Division of Cancer Treatment and Diagnosis, National Institutes of Health; 2003.Google Scholar
  9. 9.
    Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92:205–216.PubMedCrossRefGoogle Scholar
  10. 10.
    Burris HA, 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;15:2403–2413.PubMedGoogle Scholar
  11. 11.
    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 national cancer institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–1966.PubMedCrossRefGoogle Scholar
  12. 12.
    Loehrer P, Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011;29:4105–4112PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Huguet F, Andre T, Hammel P, et al. Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II et III studies. J Clin Oncol. 2007;25:3:326–331.PubMedCrossRefGoogle Scholar
  14. 14.
    Huguet F, Girard N, Guerche CS, Hennequin C, Mornex F, Azria D. Chemoradiotherapy in the management of locally advanced pancreatic carcinoma: a qualitative systematic review. J Clin Oncol. 2009;27:2269–77.PubMedCrossRefGoogle Scholar
  15. 15.
    Chauffert B, Mornex F, Bonnetain F, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Ann Oncol. 2008;19:1592–1599.PubMedCrossRefGoogle Scholar
  16. 16.
    Ammori J, Colletti L, Zalupski M, et al. Surgical resection following radiation therapy with concurrent gemcitabine in patients with previously unresectable adenocarcinoma of the pancreas. J Gastrointest Surg. 2003;7:766–72.PubMedCrossRefGoogle Scholar
  17. 17.
    Sa Cunha A, Rault A, Laurent C, et al. Surgical resection after radiochemotherapy in patients with unresectable adenocarcinoma of the pancreas. J Am Coll Surg. 2005;201:359–365.PubMedCrossRefGoogle Scholar
  18. 18.
    Conroy T, Paillot B, Francois E, et al. Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer. A Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study. J Clin Oncol. 2005;23:1228–1236.PubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Faris J, Blaszkowsky L, McDermott S, et al. Folfirinox in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience. Oncologist. 2013;18:543–548.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Gunturu KS, Yao X, Cong X, Thumar JR, Hochster HS, Stein SM, et al. Folfirinox for locally advanced and metastatic pancreatic cancer: single institution retrospective review of efficacy and toxicity. Med Oncol. 2013;30:361.PubMedCrossRefGoogle Scholar
  22. 22.
    Teh SH, Diggs B, Deveney C, Sheppard B. Patient and hospital characteristics on the variance of perioperative outcomes for pancreatic resection in the United States: a plea for outcome-based and not volume-based referral guidelines. Arch Surg. 2009;144:713–721.PubMedCrossRefGoogle Scholar
  23. 23.
    Crane CH, Abbruzzese JL, Evans DB, et al. Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer? Int J Radiat Oncol Biol Phys. 2002;52:1293–1302.PubMedCrossRefGoogle Scholar
  24. 24.
    Hartwig W, Hackert T, Hinz U, Hassenpflug M, Strobel O, Büchler MW, et al. Multivisceral resection for pancreatic malignancies: risk-analysis and long term outcomes. Ann Surg. 2009;250:81–87.PubMedCrossRefGoogle Scholar
  25. 25.
    Gillen S, Schuster T, Meyer Zum Büschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7:e1000267.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Evans DB, Erickson BA, Ritch P. Borderline resectable pancreatic cancer: definitions and the importance of multimodality therapy. Ann Surg Oncol. 2010;17(11):2803–5.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • L. Marthey
    • 1
  • A. Sa-Cunha
    • 2
  • J. F. Blanc
    • 3
  • M. Gauthier
    • 4
  • A. Cueff
    • 4
  • E. Francois
    • 5
  • I. Trouilloud
    • 6
  • D. Malka
    • 7
  • J. B. Bachet
    • 8
  • R. Coriat
    • 9
  • E. Terrebonne
    • 10
  • C. De La Fouchardière
    • 11
  • S. Manfredi
    • 12
  • D. Solub
    • 13
  • C. Lécaille
    • 14
  • A. Thirot Bidault
    • 1
  • F. Carbonnel
    • 1
  • J. Taieb
    • 6
  1. 1.Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance publique-Hôpitaux de Paris (AP-HP)Paris Sud UniversityLe Kremlin BicêtreFrance
  2. 2.Department of Digestive SurgeryHaut-Lévêque HospitalPessacFrance
  3. 3.Department of GastroenterologySaint-André HospitalBordeauxFrance
  4. 4.Department of BiostatisticsAnticancer Center G.F. LeclercDijonFrance
  5. 5.Department of OncologyAnticancer Center A. LacassagneNiceFrance
  6. 6.Department of Gastroenterology and Digestive Oncology, HEGP Hospital, Assistance publique-Hôpitaux de Paris (AP-HP)Paris Descartes University, Cancer Research Personalized Medicine (CARPEM)ParisFrance
  7. 7.Department of OncologyInstitut Gustave RoussyVillejuifFrance
  8. 8.Department of Gastroenterology, La Pitié-Salpétrière HospitalAssistance publique-Hôpitaux de Paris (AP-HP)ParisFrance
  9. 9.Department of Gastroenterology, Cochin HospitalAssistance publique-Hôpitaux de Paris (AP-HP)ParisFrance
  10. 10.Department of GastroenterologyHaut-Lévêque HospitalPessacFrance
  11. 11.Department of OncologyAnticancer Center L. BérardLyonFrance
  12. 12.Department of GastroenterologyPontchaillou HospitalRennesFrance
  13. 13.Department of OncologyL. Pasteur HospitalChartresFrance
  14. 14.Department of GastroenterologyPolyclinique Bordeaux Nord AquitaineBordeauxFrance

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