Two dosages of oral fluoropyrimidine S-1 of 35 and 40 mg/m2 bid: comparison of the pharmacokinetic profiles in Korean patients with advanced gastric cancer.

Abstract

OBJECTIVE:

In this study, we compared the pharmacokinetic profiles of 5-fluorouracil (5-FU), tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) after administration of S-1 at 35 or 40 mg/m(2) bid for 28 consecutive days, in Cycles 1 and 3, in patients with advanced gastric cancer.

METHODS:

Three patients were enrolled for each dosage. S-1 dosage was assigned based on body surface area (BSA), which is different from the Japanese dosing system. The median daily dose per BSA was 76 mg/m(2), ranging from 70 to 88 mg/m(2).

RESULTS:

Plasma levels of 5-FU, tegafur, CDHP and Oxo at 4 h post-dose reached steady-state on day 8. The estimated steady-state level was dependent on S-1 dosage. There were no intercyclic differences of pre-dose and 4 h post-dose levels between Cycles 1 and 3, implying no cumulative effect of S-1 was shown probably due to 2-week drug-resting period. Pharmacokinetic profiles on day 28 were similar to previous Japanese report. C(max) and AUC(0-48 h) values of each S-1 component increased depending on S-1 dosage. Pharmacokinetic parameters were not correlated with tumor response or toxicity.

CONCLUSIONS:

We suggest that these pharmacokinetic profiles of Asian population could provide a basis for schedule optimization and for additional studies on interaction with other antitumor drugs.

• Authors: Hei-Cheul Jeung, Sun Young Rha, Sang Joon Shin, Joong Bae Ahn, Sung Hoon Noh, Jae Kyung Roh, Hyun Cheol Chung
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 40 Issue 1 Pg. 29-35 (Jan 2010) ISSN: 1465-3621 [Electronic] England
• PMID: 19880858 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Drug Combinations
• S 1 (combination)
• Tegafur
• Oxonic Acid

Topics

• Adenocarcinoma (drug therapy)
• Adult
• Aged
• Antimetabolites, Antineoplastic (administration & dosage, blood, pharmacokinetics, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Combinations
• Female
• Humans
• Korea
• Male
• Middle Aged
• Neoplasm Staging
• Oxonic Acid (administration & dosage, blood, pharmacokinetics, therapeutic use)
• Stomach Neoplasms (drug therapy)
• Tegafur (administration & dosage, blood, pharmacokinetics, therapeutic use)
• Treatment Outcome