A phase I study of neoadjuvant chemoradiotherapy with S-1/oxaliplatin in patients with gastric cancer.

Abstract

51 Background: To determine the maximum tolerated dose (MTD) of concurrent radiotherapy with S-1 and oxaliplatin, and antitumor activity of the combination treatment in patients with gastric cancer. Methods: This was a phase I, escalating multiple-dose tolerability trial. S-1 and oxaliplatin were administered concurrently with radiotherapy for 4 weeks before surgery. The dose escalation scheme is provided in the table below. S-1 was continuously administered during radiotherapy and oxaliplatin was administered weekly for 4 weeks during radiotherapy. Results: From March 2009 to June 2010, twelve patients were entered at two dose levels. The most common dose-related grade 1 and 2 adverse events were nausea, vomiting, anorexia and abdominal pain. Two of six patients treated at level 1 developed DLT (disabling abdominal pain, stomach perforation). The dose of S-1/oxaliplatin was reduced to 30 mg/m2 bid and 40 mg/m2 (Level -1). There one DLT (vomiting and anorexia, grade 3) observed in the expanded cohort of 6 patients at Level -1. Among 12 patients, 1 patient demonstrated pathological CR after neoadjuvant chemoradiation therapy. Conclusions: Neoadjuvant CCRT with S-1/oxaliplatin was well tolerated, at a dose 30 mg/m2 bid for S-1 and 40 mg/m2 for oxaliplatin that at which antitumor activity was seen. Phase II study is planned to investigate further the efficacy, tolerability and optimal dose. [Table: see text] No significant financial relationships to disclose.