Pharmacokinetic Study of S-1 in Patients in Whom Inulin Clearance Was Measured

Ando, Yumiko; Kawada, Kenji; Inada, Megumi; Morita, Sachi; Mitsuma, Ayako; Yasuda, Yoshinari; Hiramatsu, Masayuki; Fujimoto, Yasushi; Fujita, Ken‐ichi

doi:10.1159/000337232

Cited by 5 publications

(8 citation statements)

References 22 publications

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“…As previously reported, our study demonstrated a correlation between renal function and clearance of CDHP. Of note, we performed sampling for pharmacokinetic investigation on day 8, when the plasma concentration of CDHP reached a steady state .…”

Section: Discussionsupporting

confidence: 90%

“…Of note, we performed sampling for pharmacokinetic investigation on day 8, when the plasma concentration of CDHP reached a steady state . In contrast, previous studies performed sampling for pharmacokinetics on the first day of S‐1 administration, prior to CHDP reaching a steady state . Moreover, previous studies included few patients with moderate or severe renal dysfunction .…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetic study of the oral fluorouracil antitumor agent S‐1 in patients with impaired renal function

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic study of the oral fluorouracil antitumor agent S‐1 in patients with impaired renal function

et al. 2019

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“…Renal function may also affect the deviation of the plasma concentration of S-1. Over 50% of 5-chloro-2,4-dihydroxypyrimidine is excreted in urine so that the area under the curve of the serum concentration of 5-chloro-2,4-dihydroxypyridine and tegafur is significantly related to creatinine clearance [25,26,27]. Creatinine clearance in the S-1 arm and the serum creatinine level in the GS arm were statistically higher in the low-dose group than in the high-dose group, which might affect the incidences of adverse events between the two groups.…”

Section: Discussionmentioning

confidence: 99%

Unexpected Side Effects of a High S-1 Dose: Subanalysis of a Phase III Trial Comparing Gemcitabine, S-1 and Combinatorial Treatments for Advanced Pancreatic Cancer

Kobayashi

Ueno²,

Irie³

et al. 2016

Oncology

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Objective: In this subanalysis of a phase III trial using three categorized doses of S-1, the influence of the actual doses on safety and efficacy was evaluated. Methods: We compared the efficacy and safety of the S-1 or gemcitabine plus S-1 combination (GS) arm between the top 10% group and the bottom 10% group according to the initial doses of S-1: ≥77.6 versus ≤65.9 mg/m²/day (n = 28 vs. 28) in the S-1 arm, and ≥65.1 versus ≤53.8 mg/m²/day (n = 27 vs. 28) in the GS arm. Results: Overall and progression-free survival were not significantly different between these two groups: hazard ratios of 0.818 and 0.761 with p values of 0.498 and 0.330 in the S-1 arm, and hazard ratios of 0.836 and 0.759 with p values of 0.557 and 0.323 in the GS arm, respectively. Incidences of grade 3-4 hematological toxicities were significantly higher in the top 10% group than in the bottom 10% group: 42.9 versus 14.3 and 85.2 versus 57.1%, with p values of 0.037 and 0.037 in the S-1 and the GS combination arm, respectively. Conclusions: Higher actual doses of S-1 were associated with a higher incidence of hematological toxicity even in the same dose setting.

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“…S-1 consists of three drugs: tegafur (a prodrug of fluorouracil), gimeracil (which inhibits fluorouracil degradation), and oteracil (which reduces gastrointestinal toxicity caused by fluorouracil phosphorylation) [13]. Once renal function deteriorates due to CDDP, the concentration of fluorouracil increases, leading to increased fluorouracil toxicity (because gimeracil is excreted in urine via the kidney) [13].…”

Section: Discussionmentioning

confidence: 99%

“…Once renal function deteriorates due to CDDP, the concentration of fluorouracil increases, leading to increased fluorouracil toxicity (because gimeracil is excreted in urine via the kidney) [13]. As a result, it may be necessary to avoid the use of S-1, the key medication, in certain patients.…”

Section: Discussionmentioning

confidence: 99%

Pathological Complete Response and Long-Term Survival in a Very Elderly Patient after Neoadjuvant Chemotherapy for Locally Advanced, Unresectable Gastric Cancer

Izuishi

Kobayashi

Sano

et al. 2014

Case Reports in Oncological Medicine

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We address the pathological complete response and long-term survival of elderly patients after neoadjuvant chemotherapy in locally advanced, unresectable gastric cancer. An 83-year-old man was hospitalized for upper abdominal pain. Gastrointestinal endoscopy showed a large tumor spanning from the gastric angle to the antrum, and extending to the duodenum. Histological analysis of the biopsy specimen revealed a poorly differentiated adenocarcinoma. Computed tomography images showed thickening of the gastric wall and invasion of the body and head of the pancreas, but did not show distant metastases. The patient was diagnosed with unresectable gastric cancer, and was treated with neoadjuvant chemotherapy using S-1 (80 mg/m2) and paclitaxel (60 mg/m2). After the third course of chemotherapy, gastrointestinal endoscopy and abdominal computed tomography revealed a remarkable reduction in tumor size. This reduction allowed distal gastrectomy to be conducted. Histological examination of the specimen revealed no cancer cells in the primary lesion or lymph nodes. The patient was treated with adjuvant chemotherapy of oral tegafur-uracil (300 mg/day) for one year after surgery. He lived for five years after surgery without recurrence. Neoadjuvant chemotherapy using S-1 and paclitaxel is a potent strategy for improving survival in very elderly patients with unresectable gastric cancer.

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Pharmacokinetic Study of S-1 in Patients in Whom Inulin Clearance Was Measured

Cited by 5 publications

References 22 publications

Pharmacokinetic study of the oral fluorouracil antitumor agent S‐1 in patients with impaired renal function

Pharmacokinetic study of the oral fluorouracil antitumor agent S‐1 in patients with impaired renal function

Unexpected Side Effects of a High S-1 Dose: Subanalysis of a Phase III Trial Comparing Gemcitabine, S-1 and Combinatorial Treatments for Advanced Pancreatic Cancer

Pathological Complete Response and Long-Term Survival in a Very Elderly Patient after Neoadjuvant Chemotherapy for Locally Advanced, Unresectable Gastric Cancer

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