P-087 A phase II study of a combination treatment of alternate-day S-1 and lentinan as first-line chemotherapy for unresectable or recurrent gastric cancer

Abstract

Introduction: Treatment with S‐1 plus cisplatin is a standard regimen for unresectable or recurrent gastric cancer. However, adverse events are commonly observed in this regimen, so S‐1 monotherapy is one of the treatment option especially in elderly patients. Even in the S‐1 treatment, the standard schedule of a 4‐week daily administration followed by a 2‐week rest frequently causes adverse events.We attempted an alternate‐day therapy with S‐1 plus antitumor polysaccharide lentinan to reduce the adverse events and to achieve long‐term administration. Methods: This is a phase II, multi‐institutional, prospective study. S‐1 was administered according to the schedule for the alternate‐day regimen (on Monday, Wednesday, Friday and Sunday) in the recommended dosage of 40 mg/m2 twice with weekly intravenous administration of lentinan (2mg/body) in patients with unresectable or recurrent gastric cancer. Treatment was continued until disease progression or appearance of intolerable adverse events. Eligibility criteria of the patients included no prior chemotherapy, no requirement of measurable lesions fitting RECIST, 20 years of age or older and no upper age limit. The primary endpoint was time to treatment failure (TTF). The secondary endpoints were overall survival (OS), progression‐free survival (PFS), response rate (RR) and occurrence rate of adverse events. The sample size was calculated according to the two stage design of Simon.We hypothesized that alternate‐day S‐1 regimen would be effective if the TTF reached 3 months. Therefore, the present study was designed to detect a TTF of 4.5 months as compared to a minimal TTF of 3 months, with an alpha error of 0.05 and a beta error of 0.2. The required number was estimated as 37 patients. Results: In 37 eligible patients, the median age was 74 years (46‐83 years), with 27 males and 10 females. The median TTF was 5.3 months (95% CI, 3.5‐7.1) and the median OS was 12.1 months (95% CI, 9.6‐14.6). The reason for treatment discontinuation was progressive disease in all eligible patients, so the median PFS was same as the median TTF. Of the 37 patients, 29 had measurable lesions according to RECIST. Four patients showed partial response (PR), and RR was 13.8%. Eighteen patients showed stable disease (SD). The disease control rate (PR + SD) was 75.9%. Although half of the patients ware over 74 years, adverse events were relatively mild. All grades neutropenia developed in 29.7%, and grade 3 neutropenia developed only in one patients. Non‐hematologic adverse events were rarely observed. Grade 1 anorexia, nausea, fatigue, diarrhea and stomatitis developed in 13.5, 10.8, 13.5, 10.8 and 8.1%, respectively. Only one patient experienced grade 2 anorexia. Conclusion: A combination of alternate‐day S‐1 and lentinan treatment for unresectable or recurrent gastric cancer is well‐tolerated and effective, with a favorable toxicity profile. The present combination regimen at this schedule is one of the treatment options for elderly patients.