title: Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials.
abstract: This study evaluates the efficacy of capecitabine using data from a large, well-characterised population of patients with metastatic colorectal cancer (mCRC) treated in two identically designed phase III studies. A total of 1207 patients with previously untreated mCRC were randomised to either oral capecitabine (1250 mg m(-2) twice daily, days 1-14 every 21 days; n=603) or intravenous (i.v.) bolus 5-fluorouracil/leucovorin (5-FU/LV; Mayo Clinic regimen; n=604). Capecitabine demonstrated a statistically significant superior response rate compared with 5-FU/LV (26 vs 17%; P<0.0002). Subgroup analysis demonstrated that capecitabine consistently resulted in superior response rates (P<0.05), even in patient subgroups with poor prognostic indicators. The median time to response and duration of response were similar and time to progression (TTP) was equivalent in the two arms (hazard ratio (HR) 0.997, 95% confidence interval (CI) 0.885-1.123, P=0.95; median 4.6 vs 4.7 months with capecitabine and 5-FU/LV, respectively). Multivariate Cox regression analysis identified younger age, liver metastases, multiple metastases and poor Karnofsky Performance Status as independent prognostic indicators for poor TTP. Overall survival was equivalent in the two arms (HR 0.95, 95% CI 0.84-1.06, P=0.48; median 12.9 vs 12.8 months, respectively). Capecitabine results in superior response rate, equivalent TTP and overall survival, an improved safety profile and improved convenience compared with i.v. 5-FU/LV as first-line treatment for MCRC. For patients in whom fluoropyrimidine monotherapy is indicated, capecitabine should be strongly considered. Following encouraging results from phase I and II trials, randomised trials are evaluating capecitabine in combination with irinotecan, oxaliplatin and radiotherapy. Capecitabine is a suitable replacement for i.v. 5-FU as the backbone of colorectal cancer therapy.
authors.affiliation: University Hospital Gasthuisberg, Leuven, Belgium. eric.vancutsem@uz.kuleuven.ac.be
authors.forename: E
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: P M
authors.initials: PM
authors.lastname: Hoff
authors.forename: P
authors.initials: P
authors.lastname: Harper
authors.forename: R M
authors.initials: RM
authors.lastname: Bukowski
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.forename: P
authors.initials: P
authors.lastname: Dufour
authors.forename: U
authors.initials: U
authors.lastname: Graeven
authors.forename: J
authors.initials: J
authors.lastname: Lokich
authors.forename: S
authors.initials: S
authors.lastname: Madajewicz
authors.forename: J A
authors.initials: JA
authors.lastname: Maroun
authors.forename: J L
authors.initials: JL
authors.lastname: Marshall
authors.forename: E P
authors.initials: EP
authors.lastname: Mitchell
authors.forename: G
authors.initials: G
authors.lastname: Perez-Manga
authors.forename: P
authors.initials: P
authors.lastname: Rougier
authors.forename: W
authors.initials: W
authors.lastname: Schmiegel
authors.forename: J
authors.initials: J
authors.lastname: Schoelmerich
authors.forename: A
authors.initials: A
authors.lastname: Sobrero
authors.forename: R L
authors.initials: RL
authors.lastname: Schilsky
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007275:Injections, Intravenous; D017567:Karnofsky Performance Status; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil