1. Safety and Efficacy of S-1, a Novel Oral Fluorouracil Antitumor Drug, for a Chronic Renal Failure Patient Maintained on Hemodialysis
- Author
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Tetsuo Arakawa, Masaki Hamaguchi, Eiji Sasaki, Takayuki Matsumoto, N. Oshitani, Kazunari Tominaga, Masatsugu Shiba, Hirotoshi Okazaki, Yasuhiro Fujiwara, Toshio Watanabe, Kazuhide Higuchi, Tetsuya Tanigawa, and Reiko Suto
- Subjects
Male ,Drug ,Cancer Research ,medicine.medical_specialty ,Pyridines ,medicine.drug_class ,media_common.quotation_subject ,medicine.medical_treatment ,Administration, Oral ,Pharmacology ,Tegafur ,Antimetabolite ,Drug Administration Schedule ,Pharmacokinetics ,Renal Dialysis ,Stomach Neoplasms ,medicine ,Humans ,media_common ,business.industry ,Liver Neoplasms ,General Medicine ,Prodrug ,medicine.disease ,digestive system diseases ,Surgery ,Drug Combinations ,Oxonic Acid ,Oncology ,Fluorouracil ,Kidney Failure, Chronic ,Hemodialysis ,Tomography, X-Ray Computed ,business ,medicine.drug ,Kidney disease - Abstract
Objective: S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase, and potassium oxonate (Oxo), a reducer of gastrointestinal toxicity. S-1 has safe and potent antitumor effects in patients with gastric cancer via these respective functions. However, the plasma 5-FU concentration is suspected to accumulate in patients with renal dysfunction, because 50% of the CDHP is excreted into the urine. There are no useful data on safety and efficacy of S-1 in chronic renal failure patients maintained on hemodialysis (HD). We examined the influence of HD on the pharmacokinetics (PK) of S-1 and its therapeutic efficacy in liver metastases from gastric cancer. Methods: For the HD patient, the dose of S-1 in a single-administration study was set at 50 mg/body/day (41.7% of the recommended dose of 80 mg/m2/day). S-1 was given to the patient 24 h after HD. Blood samples were obtained before administration and 2, 4, 6, 8, and 24 h thereafter and 1, 2, 4, and 72 h after the following HD session. The PK parameters (5-FU, CDHP, Oxo, and FT) were measured, and Cmax, Tmax, AUC0–24, and T1/2 were calculated. The dose of consecutive or maintained administrations was determined. Results: Both an increase in Cmax and an elongation of T1/2 for 5-FU, CDHP, and Oxo, but not for FT, occurred in this case as compared with controls. The AUC0–24 of 5-FU in this case was similar to that of controls at the standard dose. After HD, 87.8, 54.5, 77.4, and 66.2% of 5-FU, CDHP, Oxo, and FT, respectively, were eliminated. A slight accumulation of CDHP did not alter the 5-FU PK. Consecutive or maintained S-1 oral administration at the same dose showed similar effects on all PK parameters of a single-administration test. Liver metastases almost totally regressed with no adverse events 4 weeks after S-1 treatment (50 mg/body/day three times a week). Conclusion: Adjusted doses of S-1 according to the results of PK studies may provide therapeutic safety and high efficacy in liver metastases from gastric cancer, even in chronic renal failure patients maintained on HD.
- Published
- 2004
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