A drug-drug interaction study of capecitabine and celecoxib in patients with advanced solid malignancies.

e14066 Background: Warfarin is an anticoagulant and CYP2C9 substrate commonly used in oncology patients. Several studies suggest a drug-drug interaction between capecitabine and warfarin that may be mediated by CYP2C9. Celecoxib is a CYP2C9 substrate that may also have anticancer activity. We aimed to characterize the magnitude and the time course of the capecitabine-celecoxib interaction in cancer patients in order to better understand the effect of capecitabine on CYP2C9. Methods: Patients received 200 mg celecoxib PO twice daily continuously, with capecitabine (1,000 mg/m2 PO twice daily for 14 days every 21 days) starting 7 days later. Celecoxib and celecoxib-OH pharmacokinetics (PK) were collected on days 7, 14 and 21. Thirteen patients were evaluable for PK analysis. Results: Comparison of steady state PK parameters showed an average 31%, 17% and 34% increase in celecoxib’s Cmax (p = 0.036; paired t-test), Cmin (p = 0.043) and AUC (p = 0.006) between day 7 (celecoxib only) and day 14 (celecoxib + capecitabine), respectively. PK comparison of day 7 vs. day 21 (after one week washout of capecitabine) showed a further increase in Cmax (46%, p = 0.011), Cmin (92%, p = 0.002) and AUC (49%, p = 0.006). Conclusions: Coadministration of capecitabine results in higher exposure to celecoxib, and the interaction persists for at least 7 days after discontinuation of capecitabine. Clinical trial information: NCT01705106.