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.