Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001–02)

T. Aparicio (1) , S. Lavau-Denes (2) , J.M. Phelip (3) , E. Maillard (4) , J.L. Jouve (5) , D. Gargot (6) , M. Gasmi (7) , C. Locher (8) , X. Adhoute (9) , P. Michel (10) , F. Khemissa (11) , T. Lecomte (12) , J. Provençal (13) , G. Breysacher (14) , J.L. Legoux (15) , C. Lepère (16, 17) , J. Charneau (18) , J. Crétin (19) , L. Chone (20) , A. Azzedine (21) , O. Bouché (22) , I. Sobhani (23) , L. Bedenne (4, 5) , E. Mitry (24) , Ffcd Investigators

1 Service de Gastro-entérologie [Avicenne]
2 Service d'Oncologie médicale [CHU Limoges]
3 Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne]
4 Fédération Francophone de la Cancérologie Digestive, FFCD
5 Service d'Hépato-Gastro-Entérologie (CHU de Dijon)
6 CHB - Centre Hospitalier de Blois
7 Hôpital Nord [CHU - APHM]
8 Centre Hospitalier de Meaux
9 Hôpital Haut-Lévêque [CHU Bordeaux]
10 Service d'Hépato-Gastroentérologie [CHU Rouen]
11 Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan]
12 Département d'Hépato-Gastroentérologie [Hôpital Trousseau, Tours]
13 Centre Hospitalier Métropole Savoie [Chambéry]
14 Hôpital pasteur [Colmar]
15 CHRO - Centre Hospitalier Régional d'Orléans
16 HEGP - Hôpital Européen Georges Pompidou [APHP]
17 Service d'oncologie médicale [CHU HEGP]
18 Hôpital Duchenne
19 Clinique Bonnefon
20 Service d'Hépato-gastro-entérologie [CHRU Nancy]
21 Centre Hospitalier Henri Duffaut (Avignon)
22 Hôpital universitaire Robert Debré [Reims]
23 Service d'hépato-gastro-entérologie [APHP Henri Mondor]
24 Institut Curie [Paris]

BACKGROUND: Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients. PATIENTS AND METHODS: Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR). RESULTS: From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%). CONCLUSION: In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2. CLINICALTRIALSGOV: NCT00303771.

Mots clés: chemotherapy; colorectal cancer; elderly; geriatric oncology

Domaines: Cancer

T. Aparicio, S. Lavau-Denes, J.M. Phelip, E. Maillard, J.L. Jouve, et al.. Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001–02). Annals of Oncology, 2016, 27 (1), pp.121 - 127. ⟨10.1093/annonc/mdv491⟩. ⟨hal-01910082⟩