529PD - Randomized phase III in elderly patients comparing LV5FU2 with or without irinotecan for 1st-line treatment of metastatic colorectal cancer (FFCD 20...

Date 29 September 2012
Event ESMO Congress 2012
Session Gatrointestinal tumors, colorectal
Topics Anticancer agents
Geriatric Oncology
Colon and Rectal Cancer
Biological therapy
Presenter Emmanuel Mitry
Authors E. Mitry1, L. Venat-Bouvet2, J. Phelip3, E. Maillard4, J. Jouve5, X. Adhoute6, D. Gargot7, M. Gasmi8, L. Bedenne9, T. Aparicio10
  • 1Oncologie Médicale, Institut Curie, 75005 - Paris/FR
  • 2Oncology, CHU de limoges, limoges/FR
  • 3Gastroenterology, CHU, St-Etienne/FR
  • 4Biostatistiques, FFCD, Dijon/FR
  • 5Hepatogastrolentorology Department, CHU Le Bocage, 21079 - Dijon/FR
  • 6Gastroenterology, Hôpital Haut-Leveque, Pessac/FR
  • 7Gastroenterology, Centre hospitalier, Blois/FR
  • 8Hepatogastroenterology Department, Hôpital Nord, 13915 - Marseille/FR
  • 9Ffcd, FFCD, Dijon/FR
  • 10Gastroenterology, CHU, Avicenne/FR



Metastatic colorectal cancer (mCRC) most frequently occurs in elderly patients (pts), but these are less frequently treated with chemotherapy (CT) than younger ones. We report the final results of the first phase III study in elderly pts with mCRC receiving a 5FU-based CT with or without irinotecan.


Elderly pts (75+) with previously untreated mCRC were randomly assigned to receive a 5FU-based CT, either alone or in combination with irinotecan (FU arms: LV5FU2 or simplified LV5FU2, IRI arms: LV5FU2-CPT11 or FOLFIRI, reduced dosage for cycles 1 and 2). Stratification criteria were: center, Charlson index, Karnofsky index, previous adjuvant CT, sex, age, alkaline phosphatases. Primary endpoint was progression free survival (PFS). 240 events (282 pts) were required to demonstrate an improvement of median PFS from 5.5 to 7.9 months (m) in the IRI arm (bilateral α = 5%, � = 80%). Secondary endpoints were overall survival (OS), safety, objective response rate (ORR), QOL and geriatric evaluation. Kaplan-Meier estimation, log-rank tests and Cox model (HR with 95%CI) were used.


Between 06/2003-05/2010, 142 pts were randomly assigned to FU and 140 to IRI. Median age was similar in both arms 80 years (range 74-92). Main characteristics were well-balanced. Median duration of treatment was 3.5 m in FU and 4.5 m in IRI. At least one CT dose reduction was observed for 30.9% pts in FU and 52.6% pts in IRI. No significant difference was observed for the median PFS: FU 5.2 m vs IRI 7.3 m, HR = 0.84 (0.66-1.07), p = 0.15. ORR was superior in IRI arm (p = 0.002): FU 27.4% (95% CI: 20.1-35.8) vs IRI 46.3% (95% CI: 37.6-55.1). Median OS was 14.2 m in FU vs 13.3 m in IRI, HR = 0.96 (0.75-1.24). More patients presented grade 3-4 toxicities in IRI arm (76.3% vs 52.2%), mainly neutropenia (38.5% vs 5.2% of pts), diarrhea (22.2% vs 5.2% of pts) and febrile neutropenia (6.7% vs 0.7% of pts). Toxic deaths occurred in 2 pts in each arm.


In this elderly population, adding irinotecan to an infusional 5FU-based CT seems to increase PFS but does not improve survival and was associated with an increased toxicity.


E. Mitry: Aventis, Pfizer: sponsor of the trial.

All other authors have declared no conflicts of interest.