Safety evaluation of oral fluoropyrimidine S-1 for short- and long-term delivery in advanced gastric cancer: analysis of 3,758 patients.
OBJECTIVE
To evaluate the comprehensive safety profile of S-1, a promising novel oral fluoropyrimidine derivative, based on large cohort data.


METHODS
Study subjects were identified from a prospective registry of 3,758 advanced gastric cancer patients in Japan. Each patient was treated with an identical regimen of S-1 monotherapy (40 mg b.i.d. on days 1-28, every 6 weeks) and assessed for all adverse events.


RESULTS
The median duration of treatment was 88 days; 1,605 (43%) patients underwent three or more treatment cycles. The relative dose intensity was 0.87 in the first two cycles (short-term treatment period) and 0.89 thereafter (long-term treatment period). Neutropenia was the most common severe (grade 3-4) hematological event (6.3% in the short-term period and 5.3% in the long-term period). Other hematological or key gastrointestinal events (diarrhea, nausea/vomiting, and stomatitis) had a low incidence of severe cases throughout the whole administration period (0.3-3.8%). The time to onset of severe events did not differ between patients with mild renal impairment (creatinine clearance, 50-79 ml/min) and those with normal renal function (>or=80 ml/min) (hazard ratio, 1.04; 95% CI, 0.87-1.23; P = 0.691).


CONCLUSIONS
S-1 had manageable severe toxicity and allowed good compliance regardless of treatment duration. Prolonged administration of the drug was sustainable.
Yamanaka
Takeharu
T
Cancer Biostatistics Laboratory, Institute for Clinical Research, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan. yamanaka@nk-cc.go.jp
Matsumoto
Shigemi
S
Teramukai
Satoshi
S
Ishiwata
Ryota
R
Nagai
Yoji
Y
Fukushima
Masanori
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D004338:Drug Combinations; D003875:Drug Eruptions / Q000453:epidemiology; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000453:epidemiology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D012042:Registries; D013274:Stomach Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid