Phase I study of neoadjuvant chemoradiotherapy as an outpatient setting for patients with resectable advanced gastric cancer.

Abstract

84 Background: The prognosis for advanced gastric cancer remains poor because of a high rate of metastasis or recurrence. Therefore, treatment options that might improve the prognosis are needed. Radiation is expected to improve the rate of curable resection and local recurrence. To that end, neoadjuvant chemoradiotherapy with S-1 and cisplatin (CDDP) was investigated. Methods: Advanced gastric cancer patients with regional lymph nodes metastases enrolled in this study. The chemoradiotherapy consisted of S-1 on days 1–14 and CDDP on days 1 and 15. The dose range of CDDP in the study was 15 mg/m2 to 30 mg/m2. Radiation therapy was started concurrently with chemotherapy and repeated daily on days 1–5, 8–12, 15–19, and 22–26. After the initial chemoradiation therapy, the chemotherapy was repeated within 2 weeks after the termination of radiotherapy. Surgery was scheduled to take place within 6 weeks after completion of the second cycle of chemotherapy. Results: A total of 9 patients were recruited. There was no dose-limiting toxicity (DLT) in patients both 15 mg/m2 and 20 mg/m2. In the next three patients at 25 mg/m2, there were two cases with DLTs. Therefore, the recommended dose (RD) of CDDP was 20 mg/m2. Eight patients underwent surgery and all had an R0 resection. Postoperative complications occurred in two cases (pancreatic fistula and chylous ascites). However, there was no treatment-related death. The grades of histological therapeutic effect were Grade 1a in two patients, Grade 1b in one patient and Grade 2 in four patients. One patient had no viable cancer cells, which is classified as a Grade 3 histological therapeutic effect and represented a pathological CR. Conclusions: The recommended dose of CDDP is 20mg/m2 bi-weekly and its safety and feasibility as a preoperative therapy are supported in this study. Neoadjuvant chemoradiotherapy can provide remarkable shrinkage of tumors and increases in curability rate would be expected. Further clinical trials in a larger number of patients are recommended to evaluate the validation of neoadjuvant chemoradiotherapy with S-1 and CDDP as a standard treatment strategy for resectable advanced gastric cancer. Clinical trial information: UMIN000008941.