Xin Wang¹, Hua Ren², Jing Jin², Yuan Tang², Hui Fang², Ning Li², Yong-wen Song², Xue-song Chen², Tao Zhang², Wei-hu Wang², Shu-lian Wang², Yue-ping Liu², Zi-hao Yu², Xin-fan Liu², Ye-xiong Li²

¹Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences (CAMS) and Peking union   Medical College (PUMC), ²Chinese Academy of Medical Sciences (CAMS) and Peking union   Medical College (PUMC), Cancer Hospital and Institute

Objective:This phase I/II trial aimed to determine the maximum tolerated dose (MTD) and toxicity profile of S-1 with concomitant intensity modulated radiotherapy (IMRT) as an adjuvant treatment for locally advanced gastroesophageal and gastric cancer. Method: We consecutively enrolled patients with pathologically proved locally advanced gastroesophageal or gastric adenocarcinoma (T3-4N0M0 or anyTN+M0) after complete resection with negative margins (R0). IMRT was delivered of 45 Gy (1.8 Gy/fraction, 5 days/week). S-1 was administered every weekday at a dosage (mg/m2/d) of 30 (level I, n=6), 40 (level II, n=3), 50 (level III, n=6), 60 (level IV, n=3), 70 (level V, n=3), 80 (level VI, n=6). A phase II study was conducted with the recommended dose (RD) based on phase I. An experienced physicist designed the IMRT plans using a five-to-seven-field, coplanar, sliding window technique on the Pinnacle system, version 8.0-9.0. This trial was registered with ClinicalTrials.gov, number NCT 02296658. Result: From May 2010 to December 2014, 61 patients were consecutively recruited (6 with stage II, 55 with stage III, AJCC 7th). The MTD and RD of S-1 was 80mg/m2/d administered every weekday. Dose-limiting toxicities were Grade 3 nausea, anorexia and thrombocytopenia. In the phase II study, thirty seven patients (92.5%) completed radiotherapy and thirty one (77.5) completed concomitant chemotherapy. Grade 3-4 toxicities were: nausea/anorexia (5 patients, 12.5%), leukopenia (4 patients, 10.0%), vomiting (3 patients, 7.5%), esophagitis (2 patients, 5%) and neutropenia (2 patients, 5%). No patients occurred liver or kidney dysfunction or died within the 30 days after chemoradiotherapy. With a median follow-up of 20 months (range 1.5-57.7), 2-year overall survival (OS), disease-free survival (DFS), locoregional-free survival (LRFS) and distant-metastasis free survival (DMFS) were 77.6%, 65.8%, 92.8% and 73.6%, respectively. Among 61 patients, 13 patients died of disease recurrence. 15 patients developed 13 items of distant metastasis and 4 items of locoregional relapse. Conclusion: S-1 with concurrent IMRT was feasible and tolerable for locally advanced gastroesophageal and gastric cancer patients as an adjuvant setting. The MTD and RD of S-1 was 80mg/m²/d administered every weekday. Distant metastasis was the most common failure mode.

Key Words: Gastric cancer  Chemoradiotherapy  S-1