Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study.
OBJECTIVE
To compare the response rate, efficacy parameters, and toxicity profile of oral capecitabine with bolus intravenous (IV) fluorouracil plus leucovorin (5-FU/LV) as first-line treatment in patients with metastatic colorectal cancer.


METHODS
We prospectively randomized 605 patients to treatment with oral capecitabine for 14 days every 3 weeks or 5-FU/LV by rapid IV injection daily for 5 days in 4-week cycles.


RESULTS
The overall objective tumor response rate among all randomized patients was significantly higher in the capecitabine group (24.8%) than in the 5-FU/LV group (15.5%; P =.005). In the capecitabine and 5-FU/LV groups, median times to disease progression were 4.3 and 4.7 months (log-rank P =.72), median times to treatment failure were 4.1 and 3.1 months (P =.19), and median overall survival times were 12.5 and 13.3 months (P =.974), respectively. Capecitabine, compared with bolus 5-FU/LV treatment, produced a significantly lower incidence (P <.0002) of diarrhea, stomatitis, nausea, and alopecia. Patients treated with capecitabine also displayed lower incidences of grade 3/4 stomatitis and grade 3/4 neutropenia (P <.0001) leading to significantly less neutropenic fever/sepsis. Grade 3 hand-foot syndrome (P <.00001) and grade 3/4 hyperbilirubinemia were the only toxicities more frequently associated with capecitabine than with 5-FU/LV treatment.


CONCLUSIONS
Oral capecitabine was more active than 5-FU/LV in the induction of objective tumor responses. Time to disease progression and survival were at least equivalent for capecitabine compared with the 5-FU/LV arm. Capecitabine also demonstrated clinically meaningful benefits over bolus 5-FU/LV in terms of tolerability.
Hoff
P M
PM
University of Texas M.D. Anderson Cancer Center, Houston 77030-4009, USA. phoff@mdanderson.org
Ansari
R
R
Batist
G
G
Cox
J
J
Kocha
W
W
Kuperminc
M
M
Maroun
J
J
Walde
D
D
Weaver
C
C
Harrison
E
E
Burger
H U
HU
Osterwalder
B
B
Wong
A O
AO
Wong
R
R
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D013280:Stomatitis / Q000139:chemically induced; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil