RESUMO
AIM: This study focuses on the plasma disposition and metabolic activation of capecitabine (CCB) when administered alone or when combined with cetuximab (CTX). PATIENTS AND METHODS: Twenty-four chemo-naïve patients with KRAS wild-type colorectal cancer were randomized into two arms and received either CCB alone (1,000 mg/m(2) bid p.o.), followed by CCB plus CTX (loading dose (LD)=400 mg/m(2) followed by 250 mg/m(2) weekly i.v. maintenance dose) (Arm A; n=12 patients (patients)) or CCB plus CTX followed by CCB alone (Arm B; n=12 patients). Plasma samples were collected from the cubital vein and CCB, 5'-desoxy-5-fluorocytidine (5'-DFCR) and 5'-desoxy-5 fluorouridine (5'-DFUR) were quantified by a sensitive, selective reversed phase high-performance liquid chromatography (HPLC) assay. Non-compartment pharmacokinetic parameters have been calculated by Phoenix WinNonlin. RESULTS: No clinically relevant impact of CTX on CCB pharmacokinetic parameters and metabolic conversion could be detected in both arms after statistical evaluation (ANOVA). CONCLUSION: From the pharmacokinetic point of view, co-administration of CTX to CCB seems to be safe.
