Usefulness of an S-1 dosage formula: An exploratory analysis of randomized clinical trial (JCOG1001).

Abstract

288 Background: Although the S-1 dose is determined by body surface area (BSA), its blood concentration and adverse events are affected by renal function. One study had reported the clinical utility of an S-1 dosage formula for calculating the dose for target blood concentration based on renal function (Booka E. Gastric Cancer 2016;19:876-86.). The present study aimed to explore the usefulness of this formula in adjuvant chemotherapy for gastric cancer. Methods: Ad hoc analyses was performed using data from patients enrolled in a phase III trial, JCOG1001, to evaluate the role of bursectomy for resectable advanced gastric cancer. In the abovementioned trial, patients with stage II/III received adjuvant S-1 chemotherapy based on BSA. The present study calculated the S-1 dose using the following formula: 1447.8 * (14.5+0.301*CLcr+8.23*SEX [male=1, female=0])*BSA (mg/day). Patients were divided into three groups, overdosed (OD), equal dosed (ED), and underdosed (UD), by comparing the initial dosage administered with that recommended by the formula. Results: Among the 686 eligible pts, 324, 304, and 58 were respectively classified as OD/ED/UD, with the following characteristics: median age, 67.5/64/53.5 years; men 188/229/57 (58%/75%/98%); undifferentiated type, 168/172/38 (52%/57%/66%); and pStage III, 212/200/41 (65%/66%/71%). Median relative dose intensity in OD/ED/UD pts was 93.8%/108.8%/75.0% based on the formula-recommended dose. The planned adjuvant S-1 therapy was completed in 69%/74%/74%, dose reduction and treatment schedule alteration were required in 31%/21%/9% and 20%/17%/9%, and treatment was terminated due to adverse events in 25%/18%/12%. The 5-year relapse-free (RFS) and overall survival (OS) OD/ED/UD patients were 66.6%/69.2%/74.0% and 77.0%/74.3%/77.3%, in pStage II 80.2%/85.6%/93.8% and 88.3%/90.1%/100%, and pStage III 59.6%/60.4%/65.8% and 67.0%/70.0%/67.7%, respectively. OD pts had significantly higher incidences of grade 3 or higher anemia, thrombocytopenia, diarrhea, stomatitis than ED and UD pts. Conclusions: Despite no difference in survival, this formula improved treatment compliance in OD patients receiving adjuvant S-1 chemotherapy for gastric cancer.[Table: see text]