A phase II and pharmacokinetic study of first line S-1 for advanced gastric cancer in Taiwan
Journal
Cancer Chemotherapy and Pharmacology
Journal Volume
67
Journal Issue
6
Pages
1281-1289
Date Issued
2011
Author(s)
Chen J.-S.
Chao Y.
Hsieh R.-K.
Chen P.-M.
Chiou T.-J.
Chao T.-Y.
Chen L.-T.
Whang-Peng J.
Abstract
Purpose: To evaluate the efficacy, safety and pharmacokinetic profiles of S-1, which composed of tegafur (FT, a prodrug of 5-FU), 5-chloro-2,4- dihydroxypyridine and potassium oxonate (Oxo), in Taiwanese advanced gastric cancer (AGC) patients. Methods: Patients with chemo-na?ve, histologically confirmed AGC were eligible. S-1 was given orally at dose of 40, 50 or 60 mg, twice daily for patients with body surface <1.25, 1.25-1.5 and >1.5 m 2, respectively, on day 1-28 every 42 days/cycle. Results: Thirty-four patients were included. On intent-to-treat analysis, the overall response rate, median progression-free and overall survival were 35.3% [95% confidence interval (CI): 19.2-51.3%], 2.9 (95% CI: 2.4-5.8) months and 9.8 (95% CI: 6.1-NA) months, respectively. The most common grade 3-4 toxicities were anemia 23.5% and neutropenia 11.8%. There were two treatment-related mortality, which occurred in patients with suboptimal renal function underestimated by serum creatinine level at study entry. Single-dose pharmacokinetic study showed trend toward lower AUC5-FU, and higher AUCFT and AUC Oxo comparing to most Western reports. Conclusions: The efficacy, toxicity and pharmacokinetic profiles of S-1 in current study are compatible with those from other Asian populations. Accurate renal function assessment and more closely monitoring is mandatory for S-1 therapy in patients with low body mass. Literature review suggests that, besides AUC5-FU, AUC Oxo may also attribute to the difference in the compliance to S-1 between Asian and Caucasian populations. ? 2010 Springer-Verlag.
SDGs
Other Subjects
gimeracil plus oteracil potassium plus tegafur; abdominal distension; adult; advanced cancer; aged; anemia; anorexia; article; asthenia; clinical article; diarrhea; drug dose reduction; drug efficacy; drug fatality; drug response; drug safety; female; hand foot syndrome; histopathology; human; kidney function; leukopenia; liver toxicity; male; multiple cycle treatment; nausea; nephrotoxicity; neutropenia; overall survival; phase 2 clinical trial; priority journal; progression free survival; single drug dose; stomach cancer; stomatitis; Taiwan; thrombocytopenia; vomiting; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Asian Continental Ancestry Group; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Taiwan; Tegafur
Type
journal article