Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer.
OBJECTIVE
We compared oral capecitabine, administered intermittently or continuously, versus classical cyclophosphamide, methotrexate, and fluorouracil (CMF) as first-line chemotherapy for women with advanced breast cancer unsuited to more intensive regimens.


METHODS
Three hundred twenty-three eligible women were randomly assigned to capecitabine administered intermittently (1,000 mg/m(2) twice daily for 14 of every 21 days; n = 107) or continuously (650 mg/m(2) twice daily for 21 of every 21 days; n = 107), or to classical CMF (oral cyclophosphamide 100 mg/m(2) days 1 to 14 with intravenous methotrexate 40 mg/m(2) and fluorouracil 600 mg/m(2) on days 1 and 8 every 28 days; n = 109). The primary end point was quality-adjusted progression-free survival (PFS); secondary end points included PFS, overall survival (OS), objective tumor response, and adverse events. Intermittent and continuous capecitabine were to be compared first and, if similar (P > .05), combined for definitive comparisons versus CMF.


RESULTS
Quality-adjusted PFS (P = .2), objective tumor response rate (20%; P = .8), and PFS (median, 6 months; hazard ratio [HR], 0.86; 95% CI, 0.67 to 1.10; P = .2) were similar in women assigned capecitabine versus CMF. OS was longer in women assigned capecitabine rather than CMF (median, 22 v 18 months; HR, 0.72; 95% CI, 0.55 to 0.94; P = .02). Febrile neutropenia, infection, stomatitis, and serious adverse events were more common with CMF; hand-foot syndrome was more common with capecitabine.


CONCLUSIONS
Capecitabine improved OS by being similarly active, less toxic, and more tolerable than CMF. Capecitabine is a good first-line chemotherapy option for women with advanced breast cancer who are unsuited to more intensive regimens.
National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown, NSW 1450, Australia. martin.stockler@sydney.edu.au
Martin R
MR
Stockler
Vernon J
VJ
Harvey
Prudence A
PA
Francis
Michael J
MJ
Byrne
Stephen P
SP
Ackland
Bernie
B
Fitzharris
Guy
G
Van Hazel
Nicholas R C
NR
Wilcken
Peter S
PS
Grimison
Anna K
AK
Nowak
M Corona
MC
Gainford
Akiko
A
Fong
Lisa
L
Paksec
Tatiana
T
Sourjina
Diana
D
Zannino
Val
V
Gebski
R John
RJ
Simes
John F
JF
Forbes
Alan S
AS
Coates
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine; D002945:Cisplatin / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate