Abstract：Objective To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of tegafur, gimeracil and oteracil (S-1) which was used concurrently with intensity-modulated radiotherapy (IMRT) for locally advanced gastric cancer after operation. Methods We enrolled patients who were confirmed to have TxN1-3M0 gastroesophageal or gastric adenocarcinoma after complete resection with a negative margin (R0) or a positive margin (R1). IMRT was delivered at 45 Gy/25 fractions (5 fractions/week) after R0 resection or at 45 Gy with a boost dose of 10.8 Gy for anastomosis after R1 resection. S-1 was orally administered twice every day of radiotherapy at a dose of 30 mg/(m2·d)(level Ⅰ, n=6), 40 mg/(m2·d)(level Ⅱ, n=3), 50 mg/(m2·d)(level Ⅲ, n=6), 60 mg/(m2·d)(level Ⅳ, n=3), 70 mg/(m2·d)(level Ⅴ, n=3), or 80 mg/(m2·d)(level Ⅳ, n=6). ResultsTwenty-seven patients were recruited from 2010 to 2013, with a median age of 54 years (29—65 years) and a male-to-female ratio of 23 vs.4. Grade 1—3 nausea (23 patients, 85%), anorexia (23 patients, 85%), leukopenia (23 patients, 85%), fatigue (19 patients, 70%), and thrombocytopenia (14 patients, 52%) were the most common toxicities. Of four patients who developed grade 3 toxicities, two had leucopenia, and two had DLT (grade 3 nausea and anorexia in one patient at level Ⅰ;grade 3 thrombocytopenia in one patient at level Ⅲ). This study ended with none of the 6 patients who received S-1 at 80 mg/(m2·d)(level Ⅳ) developing DLT. Conclusions S-1 with concurrent IMRT is safe and tolerable for locally advanced gastric cancer patients after operation. The MTD of S-1 is 80 mg/(m2·d), which is recommended as the dose level in phase Ⅱ and Ⅲ studies, and S-1 is orally administered twice every day of radiotherapy. The DLT are nausea, anorexia, and thrombocytopenia.
. A phase Ⅰ study of concurrent S-1 and IMRT as adjuvant treatment for locally advanced gastric cancer after operation[J]. Chinese Journal of Radiation Oncology, 2014, 23(4): 282-285.
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