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


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%).


CONCLUSIONS
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.


BACKGROUND
NCT00303771.
Department of Gastroenterology, CHU Avicenne, APHP and University Paris 13, Sorbonne Paris Cité, Bobigny thomas.aparicio@avc.aphp.fr.
T
T
Aparicio
Department of Oncology, CHU Dupuytren, Limoges.
S
S
Lavau-Denes
Department of Gastroenterology, CHU Saint Etienne-Hôpital Nord, Saint Priest en Jarez.
J M
JM
Phelip
FFCD Data Center, Fédération Francophone de Cancérologie Digestive, Dijon.
E
E
Maillard
Department of Gastroenterology, CHU Le Bocage, Dijon.
J L
JL
Jouve
Department of Gastroenterology, CH Blois, Blois.
D
D
Gargot
Department of Gastroenterology, CHU Hôpital Nord, Marseille.
M
M
Gasmi
Department of Gastroenterology, CH Meaux, Meaux.
C
C
Locher
Department of Gastroenterology, CHU Haut Lévèque, Pessac.
X
X
Adhoute
Department of Gastroenterology, CHU Charles Nicolle, Rouen.
P
P
Michel
Department of Gastroenterology, CH Saint Jean, Perpignan.
F
F
Khemissa
Department of Gastroenterology, CHU Trousseau, Tours.
T
T
Lecomte
Department of Oncology, CH Chambery, Chambery.
J
J
Provençal
Department of Gastroenterology, CH Pasteur, Colmar.
G
G
Breysacher
Department of Gastroenterology, CH de la Source, Orléans.
J L
JL
Legoux
Department of Digestive Oncology, CHU Georges Pompidou, APHP, Paris.
C
C
Lepère
Department of Gastroenterology, CH Duchenne, Boulogne sur Mer.
J
J
Charneau
Department of Oncology, Clinique Bonnefon, Alès.
J
J
Cretin
Department of Gastroenterology, CHU Nancy, Vandoeuvre-les-Nancy.
L
L
Chone
Department of Gastroenterology, CH Avignon, Avignon.
A
A
Azzedine
Department of Gastroenterology, CHU Robert Debré, Reims.
O
O
Bouché
Department of Gastroenterology, CHU Henri Mondor, APHP, Créteil.
I
I
Sobhani
FFCD Data Center, Fédération Francophone de Cancérologie Digestive, Dijon Department of Gastroenterology, CHU Le Bocage, Dijon.
L
L
Bedenne
Department of Oncology, Institut Curie, Saint-Cloud University Versailles-St Quentin, St Quentin, France.
E
E
Mitry
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D016896:Treatment Outcome
D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
chemotherapy; colorectal cancer; elderly; geriatric oncology