Whereas the current analysis demonstrates selleck compound superior response rates for capecitabine vs 5-FU/LV, the overall response rates for UFT/LV and 5-FU/LV did not differ significantly between treatment arms, with a trend to a lower response rate for UFT/LV. Capecitabine is the only oral fluoropyrimidine that has demonstrated efficacy at least equivalent to that of 5-FU/LV (Mayo Clinic regimen) as first-line therapy for colorectal cancer, leading to its regulatory approval worldwide in this indication. The superior response rate observed with capecitabine compared with 5-FU/LV was seen consistently in all subpopulation analyses. Patients with poor prognostic indicators, such as poor KPS and liver metastases, were more likely to respond if treated with capecitabine than with 5-FU/LV.

The superior response rate was particularly pronounced in the subpopulation of patients who had previously received adjuvant 5-FU. However, even among patients not previously exposed to fluoropyrimidines of any kind, the response rate was superior for those receiving capecitabine. A multivariate analysis of survival to evaluate the impact of prognostic factors confirmed the primary analysis of survival, demonstrating that survival was independent of treatment administered. Evaluation of the impact of second-line treatment on survival outcomes demonstrated that poststudy treatment favoured the 5-FU/LV group, and therefore strengthens the claim that capecitabine results in efficacy at least equivalent to that achieved with 5-FU/LV.

An integrated analysis of safety data from the phase III trials has also demonstrated that capecitabine has an improved safety profile compared with 5-FU/LV, with a significantly (P<0.001) lower incidence of diarrhoea (47.7 vs 58.2%), stomatitis (24.3 vs 61.6%), nausea (37.9 vs 47.6%) and alopecia (6.0 vs 20.6%) (Cassidy et al, 2002). The only adverse event occurring significantly more frequently with capecitabine was hand-foot syndrome (53.5 vs 6.2% with 5-FU/LV, P<0.001). This cutaneous side effect is readily managed by treatment interruption and dose reduction and led to hospitalisation of only two patients (both for <24h). The lower incidence of Grade 3�C4 neutropaenia (2.3 vs 22.8%) with capecitabine compared with 5-FU/LV led to significantly (P<0.001) less neutropaenic fever/sepsis (0.2 vs 3.4%) and consequently fewer hospitalisations (Cassidy et al, 2002).

Grade 4 adverse events were more common with 5-FU/LV than with capecitabine (5.1 vs 3.0%, respectively; P=0.078), mostly comprising neutropaenia-related complications and diarrhoea. The incidence of grade 3 or 4 treatment-related adverse events during the first treatment cycle was significantly higher in patients receiving 5-FU/LV than in those receiving capecitabine (22.6 vs 9.1%, Batimastat respectively; P<0.001). The results of this integrated analysis therefore support the use of capecitabine as first-line monotherapy for advanced colorectal cancer.