A phase II and pharmacokinetic study of first line S-1 for advanced gastric cancer in Taiwan

• Published in: Cancer chemotherapy and pharmacology Vol. 67; no. 6; pp. 1281 - 1289
• Main Authors: Chen, Jen-Shi, Chao, Yee, Hsieh, Ruey-Kuen, Cheng, Ann-Lii, Chen, Po-Min, Chiou, Tzeon-Jye, Chao, Tsu-Yi, Yeh, Kun-Huei, Chen, Li-Tzong, Whang-Peng, Jacqueline
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.06.2011; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Asian Continental Ancestry Group; Biological and medical sciences; Cancer Research; Drug Combinations; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Metastasis; Oncology; Original Article; Oxonic Acid - adverse effects; Oxonic Acid - pharmacokinetics; Oxonic Acid - therapeutic use; Pharmacology. Drug treatments; Pharmacology/Toxicology; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Taiwan; Tegafur - adverse effects; Tegafur - pharmacokinetics; Tegafur - therapeutic use; Tumors; Asia; Taiwan; Chemotherapy; Phase II; Pharmacokinetic study; Gastric cancer; S-1; Malignant tumor; Stomach cancer; First line treatment; Treatment; Phase II trial; Digestive diseases; Advanced stage; Pharmacokinetics; Cancer; Gastric disease
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-010-1416-8

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-naïve, 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 AUC 5–FU , and higher AUC FT 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 AUC 5–FU , AUC Oxo may also attribute to the difference in the compliance to S-1 between Asian and Caucasian populations.