Pharmacokinetic study of the oral fluorouracil antitumor agent S‐1 in patients with impaired renal function. Issue 6 (11th May 2019)

• Record Type: Journal Article
• Authors: Goto, Keiko; Fujiwara, Yutaka; Isobe, Takeshi; Chayahara, Naoko; Kiyota, Naomi; Mukohara, Toru; Tsubata, Yukari; Hotta, Takamasa; Tamura, Kenji; Yamamoto, Noboru; Minami, Hironobu
• Is Part Of: Cancer science. Volume 110:Issue 6(2019)
• Page Start: 1987
• Page End: 1994
• Publication Date: 2019-05-11
• Subjects: 5‐fluorouracil -- CDHP -- clearance -- eGFR -- S‐1; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14025
• Languages: English
• ISSNs: 1347-9032

Abstract

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 m 2 ), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m 2 ), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m 2 ), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m 2 ). 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. Abstract : This is the first prospective pharmacokinetic (PK) study investigating whether dose reduction of S‐1 on the basis of renal function is appropriate in patients with impaired renal function. The results indicated that the strategy for dose adjustment of S‐1 we used in this study based on body surface area and renal function was pharmacokinetically acceptable.