Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study.
OBJECTIVE
To compare the efficacy and safety of orally administered capecitabine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidine carbamate designed to mimic continuous fluorouracil (5-FU) infusion but with preferential activation at the tumor site, with that of intravenous (IV) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer.


METHODS
We prospectively randomized 602 patients to treatment with capecitabine 1,250 mg/m(2) administered twice daily days 1 to 14 every 3 weeks, or to the 4-weekly Mayo Clinic regimen (5-FU/LV) until disease progression or unacceptable toxicity.


RESULTS
The primary objective, to demonstrate at least equivalent response rates in the two treatment groups, was met. The overall response rate was 18.9% for capecitabine and 15.0% for 5-FU/LV. In the capecitabine and 5-FU/LV groups, respectively, median time to disease progression was 5.2 and 4.7 months (log-rank P =.65); median time to treatment failure was 4.2 and 4.0 months (log-rank P =.89); and median overall survival was 13.2 and 12.1 months (log-rank P =.33). The toxicity profiles of both treatments were typical of fluoropyrimidines. However, capecitabine led to significantly lower incidences (P <.00001) of stomatitis and alopecia, but a higher incidence of cutaneous hand-foot syndrome (P <.00001). Capecitabine also resulted in lower incidences (P <.00001) of grade 3/4 stomatitis and neutropenia, leading to a lower incidence of grade 3/4 neutropenic fever and sepsis. Only grade 3 hand-foot syndrome (P <.00001) and uncomplicated grade 3/4 hyperbilirubinemia (P <.0001) were reported more frequently with capecitabine.


CONCLUSIONS
Oral capecitabine achieved an at least equivalent efficacy compared with IV 5-FU/LV. Capecitabine demonstrated clinically meaningful safety advantages and the convenience of an oral agent.
Van Cutsem
E
E
Department of Internal Medicine, University Hospital Gasthuisberg, Leuven, Belgium. eric.vancutsem@uz.kuleuven.ac.be
Twelves
C
C
Cassidy
J
J
Allman
D
D
Bajetta
E
E
Boyer
M
M
Bugat
R
R
Findlay
M
M
Frings
S
S
Jahn
M
M
McKendrick
J
J
Osterwalder
B
B
Perez-Manga
G
G
Rosso
R
R
Rougier
P
P
Schmiegel
W H
WH
Seitz
J F
JF
Thompson
P
P
Vieitez
J M
JM
Weitzel
C
C
Harper
P
P
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D016019:Survival Analysis
D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D003841:Deoxycytidine; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil