Capecitabine as adjuvant treatment for stage III colon cancer.
BACKGROUND
Intravenous bolus fluorouracil plus leucovorin is the standard adjuvant treatment for colon cancer. The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer. We evaluated capecitabine in the adjuvant setting.


METHODS
We randomly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine (1004 patients) or bolus fluorouracil plus leucovorin (Mayo Clinic regimen; 983 patients) over a period of 24 weeks. The primary efficacy end point was at least equivalence in disease-free survival; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines.


RESULTS
Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group (in the intention-to-treat analysis, P<0.001 for the comparison of the upper limit of the hazard ratio with the noninferiority margin of 1.20). Capecitabine improved relapse-free survival (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99; P=0.04) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin (P<0.001).


CONCLUSIONS
Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer.
University of Leeds and Bradford NHS Hospitals' Trust, Leeds, United Kingdom. c.twelves@bradford.ac.uk
Chris
C
Twelves
Alfred
A
Wong
Marek P
MP
Nowacki
Markus
M
Abt
Howard
H
Burris
Alfredo
A
Carrato
Jim
J
Cassidy
Andrés
A
Cervantes
Jan
J
Fagerberg
Vassilis
V
Georgoulias
Fares
F
Husseini
Duncan
D
Jodrell
Piotr
P
Koralewski
Hendrik
H
Kröning
Jean
J
Maroun
Norbert
N
Marschner
Joseph
J
McKendrick
Marek
M
Pawlicki
Riccardo
R
Rosso
Johannes
J
Schüller
Jean-François
JF
Seitz
Borut
B
Stabuc
Jerzy
J
Tujakowski
Guy
G
Van Hazel
Jerzy
J
Zaluski
Werner
W
Scheithauer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016019:Survival Analysis
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil