Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial.
OBJECTIVE
Complete resection of liver metastases of colorectal origin is the only potentially curative treatment. In order to decrease recurrences, the use of adjuvant systemic chemotherapy after liver resection is controversial because no randomized study demonstrated its benefit.


METHODS
In a multicenter trial, we randomly assigned 173 patients with completely resected (R0) hepatic metastases from colorectal cancer to surgery alone and observation (87 patients) or to surgery followed by 6 months of systemic adjuvant chemotherapy with a fluorouracil and folinic acid monthly regimen (86 patients). The main outcome criterion was disease-free survival. Secondary outcome measures were overall survival and treatment-related toxicity.


RESULTS
The intention-to-treat analysis was based on 171 patients, after a median follow-up of 87 months (SE = 5.8). The 5-year disease-free survival rate, after adjustment for major prognostic factors, was 33.5% for patients in the chemotherapy group and 26.7% for patients in the control group (Cox multivariate analysis: odds ratio for recurrence or death = 0.66; 95% CI, 0.46 to 0.96; P = .028). With regard to secondary outcome measures, a trend towards increased overall survival was observed but did not reach statistical significance (5-year overall survival: chemotherapy group, 51.1% v control group, 41.1%; odds ratio for death, 0.73; 95% CI, 0.48 to 1.10; P = .13).


CONCLUSIONS
Despite a suboptimal regimen, which was the standard at the beginning of the study, adjuvant intravenous systemic chemotherapy provided a significant disease-free survival benefit for patients with resected liver metastases from colorectal cancer.
Portier
Guillaume
G
Chirurgie Digestive, CHU Purpan, place du Dr. Baylac, 31059 Toulouse, France. portier.g@chu-toulouse.fr
Elias
Dominique
D
Bouche
Olivier
O
Rougier
Philippe
P
Bosset
Jean-François
JF
Saric
Jean
J
Belghiti
Jacques
J
Piedbois
Pascal
P
Guimbaud
Rosine
R
Nordlinger
Bernard
B
Bugat
Roland
R
Lazorthes
Franck
F
Bedenne
Laurent
L
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005602:France; D006498:Hepatectomy; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D016019:Survival Analysis; D013557:Switzerland; D016896:Treatment Outcome
D002955:Leucovorin; D005472:Fluorouracil