Celecoxib in combination with irinotecan (CPT-11), 5-fluorouracil and leucovorin in patients with advanced cancer: A phase I, pharmacokinetic study

2092 Background: We demonstrated in preclinical model that CPT-11 induced diarrhea can be prevented by celecoxib. Higher doses of CPT-11 could be administered with celecoxibin vivo resulting in improved therapeutic efficacy. Methods: In this phase I study, we escalated CPT-11 dose in FOLFIRIregimen with a fixed dose of celecoxib. We also investigated potential pharmacokinetic (PK) modulation of CPT-11 by celecoxib. CPT-11 dose escalation was planned in 4 dose levels (DL): 180, 200, 220 and 260 mg/m2 along with standard doses of 5-fluorouracil and leucovorin in FOLFIRIschedule administered 2-weekly. Celecoxibwas administered in dose of 400 mg p.o. bid, starting day 2 of cycle 1. PK of CPT-11, SN-38and SN-38G were obtained on day 1 (pre- celecoxib) and day 14 (with celecoxib) in 3 patients (pts) with complete sampling. Standard 3+3 dose escalation schema was used. Plasma concentrations of CPT-11, SN-38, and SN-38G were analyzed with validated HPLC method with fluorescence detection. PK parameters assess...