In:
Oncology, S. Karger AG, Vol. 66, No. 5 ( 2004), p. 358-364
Abstract:
〈 i 〉 Objective: 〈 /i 〉 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. 〈 i 〉 Methods: 〈 /i 〉 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/m 〈 sup 〉 2 〈 /sup 〉 /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 C 〈 sub 〉 max 〈 /sub 〉 , T 〈 sub 〉 max 〈 /sub 〉 , AUC 〈 sub 〉 0–24 〈 /sub 〉 , and T 〈 sub 〉 1/2 〈 /sub 〉 were calculated. The dose of consecutive or maintained administrations was determined. 〈 i 〉 Results: 〈 /i 〉 Both an increase in C 〈 sub 〉 max 〈 /sub 〉 and an elongation of T 〈 sub 〉 1/2 〈 /sub 〉 for 5-FU, CDHP, and Oxo, but not for FT, occurred in this case as compared with controls. The AUC 〈 sub 〉 0–24 〈 /sub 〉 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). 〈 i 〉 Conclusion: 〈 /i 〉 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.
Type of Medium:
Online Resource
ISSN:
0030-2414
,
1423-0232
Language:
English
Publisher:
S. Karger AG
Publication Date:
2004
detail.hit.zdb_id:
1483096-6
detail.hit.zdb_id:
250101-6
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