Pharmacokinetic (PK) interactions between capecitabine (X), oxaliplatin (O) and bevacizumab (A) when used in combination for first-line treatment of metastatic colorectal cancer (MCRC)

2554 Background: X + O in combination (XELOX) has similar efficacy to FOLFOX-4 in untreated MCRC patients (pts) [1]. The addition of A to irinotecan/5-FU/LV improves progression-free survival (PFS) and overall survival [2], and the potential improvement of adding A to XELOX in MCRC is currently being investigated. Here we present the first PK evaluation of the effects of X on O, O on X, X+A on O, and O+A on X in a multicenter open-label study of pts with untreated MCRC. Methods: Pts received treatment for up to 16 cycles with blood samples for PK analysis taken during cycles 1–3. Treatment: cycle 1: X 1000 mg/m2 orally on morning of d1, O 130 mg/m2 i.v. infusion d2, X 1000 mg/m2 bid orally d5–14, rest d15–21; cycle 2: O 130 mg/m2 i.v. infusion d1 + X 1000 mg/m2 bid orally d1–14, rest d15–21; cycle 3 (XOA): A 7.5 mg/kg i.v. infusion d1 + O 130 mg/m2 i.v. infusion d1 + X 1000 mg/m2 bid orally d1–14, q3w. Treatment with the XOA regimen continued for a further 13 cycles. Safety was evaluated throughout. Results: 36 pts were enrolled; 26 pts completed cycles 1–3 and were evaluable for PK analysis; all pts were evaluable for safety. Baseline characteristics were: M/F 42%/58%; median age 60 years (range 22–74). The primary parameter for PK analysis of X, AUC0-8 of 5’-DFUR, was slightly lower in cycle 2 d1 (XO) and cycle 3 d1 (XOA) vs. cycle 1 d1 (X) (10% and 13% lower, respectively, with CV 27–33%); a decrease in the Cmax of 5’-DFUR was also observed (26% and 36% lower, respectively, with CV 48–54%). However these differences were not considered clinically important. The primary parameter for PK analysis of O, AUC0-8 of free platinum, was very similar among cycle 2 d1 (XO), cycle 3 d1(XOA), and cycle 1 d2 (O), with geometric mean ratios very close to 1. Treatment with X, O and A in combination was generally well tolerated. Conclusions: No large differences in exposure of X or its metabolites, free platinum or total platinum occur when X, O and A are administered in combination. This provides further support for the development of the above dosing regimen in MCRC. References: 1. Cassidy J et al. J Clin Oncol 2004;22:2084–91. 2. Hurwitz H et al. N Eng J Med 2004;350:2335–42. No significant financial relationships to disclose.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.