A multicenter phase II study of combination therapy with oral S-1 plus cisplatin in elderly patients with advanced gastric cancer.

Abstract

157 Background: The incidence of gastric cancer increases gradually in individuals aged ≥ 75 years who account for about 40% of all patients. From the SPIRITS study, comparing S-1 monotherapy with S-1 and cisplatin (CDDP) combination therapy (median overall survival [OS]: 11.0 versus 13.0 months, p=0.04), S-1 and CDDP chemotherapy (SP regimen) is recognized as one of the standard first-line regimens for patients with advanced gastric cancer in Japan. However, patients in this trial were aged < 75 years. Methods: The aim of this phase II study was to evaluate the efficacy and safety of SP regimen in elderly patients with chemotherapy-naive advanced gastric cancer. Patients aged ≥ 76 years were given oral S-1 twice daily for 21 days, followed by 14 days rest; CDDP was intravenously infused at day 8, repeated every 35 days, for up to eight cycles. The dose of S-1 (50–120 mg/body) and CDDP (30–60 mg/m2) was adjusted depending on the patient’s body surface area and creatinine clearance (Ccr-adjusted SP regimen). The primary endpoint was OS. The threshold and expected OS were estimated at 8 and 14 months, respectively. Secondary endpoints included response rate (RR), progression-free survival (PFS), time to treatment failure (TTF) and adverse events. Results: From December 2012 to October 2014, 40 patients were enrolled at 15 institutions. Patient characteristics were: gender (M/F) 29/11; median age 78 (range, 76–89); ECOG PS0/1, 13/27; and unresectable/recurrence 30/10. The median cycle for each patient was four (range, 1–8). The median OS was 12.3 months (80% confidence interval, 10.2–14.4 months). The median PFS and TTF were 7.8 and 4.3 months, respectively. The RR was 54%. A dose reduction of S-1 and CDDP was made for 30% and 35% of patients, respectively. The protocol was discontinued in 17 patients (43%) for disease progression, 10 patients (25%) for adverse events and 7 patients (17%) for patient refusal. The main adverse events at a grade 3 or higher were anorexia (25%), neutropenia (23%), hyponatremia (20%) and anemia (18%). Treatment-related deaths did not occur. Conclusions: Ccr-adjusted SP regimen showed promising activity and was tolerated well by elderly patients with advanced gastric cancer. Clinical trial information: UMIN000009349.