A study of the pharmacokinetics of 5-FU when S-1 was administered orally as an adjuvant agent in gastric cancer patients

Abstract

15024 Background: S-1 is an effective oral anti-cancer drug which is formulation of 5-FU, and it is widely used for gastric cancers in Japan. However, the compliance of S-1 treatment is not satisfactory due to its side effects. We hypothesized that the plasma concentration of 5-FU could be verified individually, because the drug is administered orally. Therefore, we investigated the pharmacokinetics of 5-FU when it was administered orally in the form of S-1. Methods: The plasma concentration of 5-FU after S-1 oral administration for adjuvant chemotherapy was measured in 22 advanced gastric cancer patients (Stage II or III). Total gastrectomy was performed in 12 patients and distal gastrectomy was performed in 10 patients. All patients were given S-1 (80mg/m2) orally at 8:00 and 20:00, daily. Blood samples were collected at 10:00, 12:00, 14:00 and 16:00 on the 7th day after S-1 administration and we measured 5-FU concentration of plasma. Results: Pharmacokinetic parameters of plasma concentration of 5-FU were as follows: Cmax, 157.92 ± 42.9 ng/ml; Tmax, 2.36 ± 0.79 h; T1/2, 2.90 ± 2.36 h; and AUC 0–8 ,731.8 ± 236.4 ng ·h/ml in all patients given the usual dosage. The plasma concentration of 5-FU was quite different between patients. The difference of Cmax and AUC was 3∼ 4 times. The AUC0- 8 in the total gastrectomy patients (752.6± 273.3 ng·h/ml) was higher than that in distal gastrectomy patients (714.5±211.7 ng·h/ml), however this difference did not reach significance. Adverse events of more than grade 3 were observed in 7 patients. AUC0–8 of 4 of 7 patients were more than 800 ng·h/ml and those of 2 other patients were more than 750 ng·h/ml. The patients with high AUC0–8 levels had a tendency to show more severe adverse events. Conclusions: We conclude that physicians should pay close attention to individual differences in the plasma concentration of 5-FU in postoperative gastric cancer patients when this drug is given orally as S- 1. No significant financial relationships to disclose.