In:
Oncology, S. Karger AG, Vol. 66, No. 5 ( 2004), p. 358-364
Kurzfassung:
〈 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.
Materialart:
Online-Ressource
ISSN:
0030-2414
,
1423-0232
Sprache:
Englisch
Verlag:
S. Karger AG
Publikationsdatum:
2004
ZDB Id:
1483096-6
ZDB Id:
250101-6
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