Analysis of risk factors for severe adverse effects of oral 5-fluorouracil S-1 in patients with advanced gastric cancer.
BACKGROUND
S-1 is an oral fluoropyrimidine that promises better and accessible treatment. This article identifies the risk factors for severe adverse events of S-1 from nationwide survey data.


METHODS
Advanced gastric cancer patients scheduled to receive S-1 monotherapy (80 mg/day for days 1-28, every 6 weeks) were registered throughout Japan between 1999 and 2000 (n = 3758). Univariate and multivariate analyses were performed to explore the risk factors for severe adverse events.


RESULTS
A multivariate analysis revealed that grade 3 or 4 neutropenia was significantly associated with baseline renal function [odds ratios (ORs) corresponding to creatinine clearance (ml/min) ranges of 50-79, 30-49, and <30 in reference to >80 increased to 1.21, 1.79, and 2.43, respectively], and the estimated incidence probability of grade 3 or 4 neutropenia ranged from 5.0% to 33.7% depending on the initial status of renal function and baseline neutrophil count. Some prior chemotherapeutic drug use may be implicated in the experience of adverse events; decreases in hemoglobin, nausea/vomiting, and hyperbilirubinemia were observed to be influenced by the previous use of irinotecan (OR = 3.07, P = 0.003), mitomycin (OR = 2.28, P = 0.004), and cisplatin (OR = 1.60, P = 0.007), respectively.


CONCLUSIONS
These findings identified possible risk factors for severe adverse events of S-1 and the patient subgroups at potentially higher risk from its administration. The results will facilitate safer administration of S-1 and thus promote enhanced tolerability and efficacy.
Yamanaka
Takeharu
T
Cancer Biostatics Laboratory, Institute for Clinical Research, National Kyushu Cancer Center, 3-1-1 Notame, Fukuoka, Japan.
Matsumoto
Shigemi
S
Teramukai
Satoshi
S
Ishiwata
Ryota
R
Nagai
Yoji
Y
Fukushima
Masanori
M
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D003404:Creatinine / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D006306:Health Surveys; D006801:Humans; D007564:Japan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D018365:Neoplasm, Residual / Q000188:drug therapy; D009504:Neutrophils / Q000378:metabolism; D010094:Oxonic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D010976:Platelet Count; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000009:adverse effects* / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D003404:Creatinine