Gemcitabine plus combinatie FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, en oxaliplatine) geeft significant mediaan langere overlevingstijd voor patienten met uitgezaaide alvleesklierkanker dan met gemcitabine alleen. Artikel update 9 mei 2012
13 mei 2011: Bron: NEJM 12 mei 2011
Van onderstaande studie zijn nieuwe resultaten vrijgekomen die aangeven dat de chemo combinatie FOLFIRINOX veruit betere resultaten geeft dan gemcitabine voor uitgezaaide alvleesklierkanker. Hoewel de toxiciteit wel zorgen baart pleiten onderzoekers en artsen ervoor de FOLFIRINOX behandeling standaard eerste lijns te maken. Hier het abstract van de studie zoals gepubliceerd in het NEJM afgelopen week waar u ook het volledige studierapport tegen betaling in kunt zien:
FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
N Engl J Med 2011; 364:1817-1825 May 12, 2011
Background
Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.
Methods
We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival.
Results
The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001).
Conclusions
As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.)
Presented in part at the 43rd annual meeting of the American Society of Clinical Oncology, Chicago, June 1–5, 2007 (phase 2) and at the 46th annual meeting of the American Society of Clinical Oncology, Chicago, June 3–8, 2010 (phase 3).
Supported by Clinical Research Hospital Program grants (PHRC 2004 and 2007) from the French Ministry of Health, and grants from Amgen and the French National League against Cancer.
Dr. Ducreux reports receiving consulting fees from Pfizer, serving on an advisory board for Sanofi-Aventis, receiving payment for the development of educational presentations from Pfizer and Sanofi-Aventis, and receiving grant support to his institution from Pfizer; Dr. Bennouna, serving on advisory boards for Roche, Boehringer, and Bayer, receiving lecture fees from Roche, AstraZeneca, and Amgen, and receiving travel fees from Boehringer and Roche; Dr. Bouché, serving on advisory boards for Roche and Pfizer; Dr. Ychou, serving on advisory boards for Amgen, Bayer, Merck, Novartis, and Roche; and Dr. Bachet, receiving payment for the development of an educational presentation from Janssen-Cilag. No other potential conflict of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank the brave patients who participated in this study, their families for their trust, all participating investigators (listed in the Supplementary Appendix), and their supporting staff. We also thank the members of the independent data and safety monitoring board (B. Asselain, E. François, E. Gamelin, and C. Louvet) for their sound advice; V. Laurent-Croisé and D. Régent for radiologic review of tumor responses; and Miller Medical Communications for medical-writing support.
Source Information
From Nancy University and Centre Alexis Vautrin, Nancy (T.C.); Centre Léon Bérard, Lyon (F.D., C.F.); Centre Val d'Aurelle (M.Y., S.G.-B.) and Centre Hospitalo-Universitaire Saint-Eloi (E.A.), Montpellier; Centre Hospitalier Universitaire Robert Debré, Reims (O.B.); Institut Claudius Regaud, Toulouse (R.G.); Institut Bergonié, Bordeaux (Y.B.); Centre Oscar Lambret, Lille (A.A.); Centre Eugène Marquis, Rennes (J.-L.R.); Centre René Gauducheau, Nantes (J.B.); Hôpital Ambroise Paré, Boulogne-Billancourt (J.-B.B.); Centre Hospitalier, Perpignan (F.K.-A.); Hôpital de la Croix Rousse, Lyon (D.P.-V.); Centre Hospitalier Henri Mondor, Créteil (C.D.); Centre Georges-François Leclerc, Dijon (B.C.); Rouen University Hospital and University of Rouen, Rouen (P.M.); Unicancer–Bureau d'Etudes Cliniques et Thérapeutiques, Paris (C.M.-G.); Institut Gustave Roussy, Villejuif (M.D.); and Paris-Sud 11 University, Le Kremlin-Bicêtre (M.D.) — all in France.
Address reprint requests to Dr. Conroy at the Department of Medical Oncology, Centre Alexis Vautrin, 54511 Vandoeuvre-lès-Nancy CEDEX, France, or at t.conroy@nancy.fnclcc.fr.
Additional investigators are listed in the Supplementary Appendix, available at NEJM.org.
16 juni 2010: bron: J Clin Oncol 28:7s, 2010 (suppl; abstr 4010)
Gemcitabine is al vele jaren een standaard chemo voor de behandeling van pancreaskanker - alvleesklierkanker, alleen of meer recentelijk gebruikt in combinatie met erlotinib (Tarceva), maar de nieuwste resultaten suggereren dat deze moet worden vervangen door de combinatie FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan,
Randomized phase III trial comparing FOLFIRINOX (F: 5FU/leucovorin [LV], irinotecan [I], and oxaliplatin [O]) versus gemcitabine (G) as first-line treatment for metastatic pancreatic adenocarcinoma (MPA): Preplanned interim analysis results of the PRODIGE 4/ACCORD 11 trial.Sub-category: Pancreatic Cancer Category: Gastrointestinal (Noncolorectal) Cancer Meeting: 2010 ASCO Annual Meeting Citation: J Clin Oncol 28:7s, 2010 (suppl; abstr 4010) Abstract No: 4010 |
Author(s): T. Conroy, F. Desseigne, M. Ychou, M. Ducreux, O. Bouche, R. Guimbaud, Y. Becouarn, C. Montoto-Grillot, S. Gourgou-Bourgade, A. Adenis, FNCLCC-FFCD PRODIGE Group; Centre Alexis Vautrin, Vandoeuvre les Nancy, France; Centre Léon Berard, Lyon, France; Centre Val d'Aurelle, Montpellier, France; Institut Gustave Roussy, Villejuif, France; University Hospital Robert Debre, Reims, France; University Hospital of Purpan, Toulouse, France; Institut Bergonié, Bordeaux, France; Fédération Nationale des Centres de Lutte Contre le Cancer, Paris, France; Centre Oscar Lambret, Lille, France
Abstract:
Background: In a randomized phase II trial of F vs G in 88 MPA patients (pts), we reported that F induces a response rate > 30% (Ychou, ASCO 2007). Because the trial met its planned objectives, it has been pursued as a phase III to compare overall survival (OS).
Methods: Chemotherapy-naïve pts aged 18-75 years with histologically/cytologically-confirmed measurable MPA were randomized to receive F (O 85 mg/m2 d1 + I 180 mg/m2 d1 + LV 400 mg/m2 d1 followed by 5FU 400 mg/m2 bolus d1 and 2,400 mg/m2 46h continuous infusion biweekly) or G (1g/m2 IV weekly x7, 1 w rest, then weekly x 3q4w). Eligibility included adequate organ function, performance status (PS) 0-1, no prior chemotherapy or radiotherapy. Pts were stratified by centre, PS, and primary tumor location (head vs. other). The primary endpoint was OS. With a planned sample size of 360 pts, the trial was designed to detect an improvement from 7 to 10 months (m) median survival (HR = 0.70) with 80% power and α = 0.05.
Results: 342 pts were enrolled between 01/2005 and 10/2009. Pts were well balanced for baseline characteristics: male 63%; median age 60 years; PS 0 38%. At the planned interim analysis, the Independent Data Monitoring Committee recommended to stop the study. Among 250 treated and monitored pts, median relative dose-intensities of 5FU, I, O and G were 0.81, 0.80, 0.78 and 1.01 respectively. Grade 3/4 toxicities per pts (%) in arms F/G were diarrhea 12.3/1.6, nausea 15.6/6.3, vomiting 17.2/6.3, fatigue 24/14.3, neutropenia 47.9/19.2 and febrile neutropenia 5.7/0. No toxic death occurred. Confirmed response rates (F/G) were 27.6% and 10.9% (p = 0.0008). Median follow-up was 19.5 m. Median PFS was 6.4/3.4 m (p < 0.0001). As of 09/2009, median OS was 10.5/6.9 m (HR = 0.61; 95%CI = 0.46-0.81; p < 0.001).
Conclusions: F is the first non containing G therapy that has shown a significantly longer OS, PFS and higher response rate than G alone. The toxicities of this regimen are manageable and F may emerge as a new standard for treatment of MPA in pts with good PS. Final analysis on the total population will be presented.
