Institution: | 1. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;2. Department of Medical Oncology and Hematology, Kobe University Graduate School of Medicine, Kobe, Japan;3. https://orcid.org/0000-0001-6981-0800;4. Department of Experimental Therapeutics, National Cancer Center Hospital, Shimane, Tokyo;5. Division of Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan;6. Yutaka Fujiwara, Department of Medical Oncology and Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.;7. Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Shimane University, Shimane, Japan;8. Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan;9. Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan |
Abstract: | Although dose reduction of S‐1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5‐fluorouracil, 5‐chloro‐2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S‐1 in patients with renal impairment. We classified patients receiving S‐1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S‐1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m2), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m2), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m2), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m2). Those in cohorts 3 and 4 treated with an adjusted dose of S‐1 showed a similar area under the curve for 5‐fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S‐1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S‐1 in patients with impaired renal function using eGFR is appropriate and safe. |