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. Conclusion. 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.