Pharmacokinetic Study of Two Infusion Schedules of Irinotecan Combined with Cisplatin in Patients with Advanced Gastric Cancer

Abstract

Objective: Irinotecan (CPT-11) in combination with cisplatin (CDDP) has shown promising antitumor activity for advanced gastric cancer, but the optimal administration schedule of CPT-11 is still controversial. To clarify the pharmacokinetic effects of different CPT-11 administration schedules, we compared two different regimens (continuous infusion of CPT-11 for 24 h and CPT-11 infusion for 90 min) combined with CDDP in patients with advanced gastric cancer. Patients and Methods: Five patients were treated with CPT-11 at a dose of 60 mg/m² delivered by continuous infusion for 24 h on day 1 and by a 90-min infusion on day 15, together with CDDP daily administered at a dose of 10 mg/m² on days 1–3 and days 15–17 for 4 weeks. The pharmacokinetics of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were investigated, as well as the toxicity of therapy. Results: Grade 3 leukopenia was observed in 1 patient after 24-hour infusion and in 1 patient after 90-min infusion of CPT-11. In addition, grade 3 thrombocytopenia was observed in 1 patient after the 90-min infusion. Other adverse reactions were mild, and the planned dose was delivered to all patients. The area under the plasma concentration-time curve of SN-38, the active metabolite from CPT-11, was increased by 24-hour infusion when compared with the 90-min infusion, and there was no increase in toxicity. Conclusion: Protracted infusional CPT-11 combined with CDDP is a practical regimen, and may be appropriate for a future phase II trial.