Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer.
OBJECTIVE
The administration of fluorouracil (5-FU) by continuous intravenous infusion (CI) is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancer. Although more than 1,200 patients have been enrolled onto randomized trials that compared these two treatment modalities, there is still no definitive evidence of an advantage of 5-FU CI, and the magnitude of this advantage, if any, is also controversial. A meta-analysis was performed to assess this benefit in terms of tumor response and survival, and to compare the toxicity profiles of these two modalities of administration of 5-FU.


METHODS
Individual data of 1,219 patients included in six randomized trials served as the basis for this meta-analysis, which was conducted by an independent secretariat in close collaboration with the investigators.


RESULTS
Tumor response rate was significantly higher in patients assigned to 5-FU CI than in patients assigned to 5-FU bolus (22% v 14%; overall response odds ratio, 0.55; 95% confidence interval [95% CI], 0.41 to 0.75; P = .0002). Overall survival was also significantly higher in patients assigned to 5-FU CI (overall hazards ratio [HR], 0.88; 95% CI, 0.78 to 0.99; P = .04), although the median survival times were close. Multivariate analyses showed that randomized treatment and performance status were the only two significant predictors of tumor response, whereas the same plus primary tumor site were independent significant predictors of survival (patients with rectal cancer did somewhat better). Grade 3 or 4 hematologic toxicity was more frequent in patients assigned to 5-FU bolus (31% v 4%; P < 10(-16)), whereas hand-foot syndrome was more frequent in the 5-FU CI group (34% v 13%; P < 10(-7)).


CONCLUSIONS
5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival. The hematologic toxicity is much less important in patients who receive 5-FU CI, but hand-foot syndrome is frequent in this group of patients.
Piedbois
P
P
Rougier
P
P
Buyse
M
M
Pignon
J
J
Ryan
L
L
Hansen
R
R
Zee
B
B
Weinerman
B
B
Pater
J
J
Leichman
C
C
Macdonald
J
J
Benedetti
J
J
Lokich
J
J
Fryer
J
J
Brufman
G
G
Isacson
R
R
Laplanche
A
A
Levy
E
E
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil