PURPOSE: To evaluate the comprehensive safety profile of S-1, a promising novel oral fluoropyrimidine derivative, based on large cohort data. PATIENTS AND 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.
PURPOSE: To evaluate the comprehensive safety profile of S-1, a promising novel oral fluoropyrimidine derivative, based on large cohort data. PATIENTS AND METHODS: Study subjects were identified from a prospective registry of 3,758 advanced gastric cancerpatients 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.