A phase I study of concurrent S-l and IMRT as adjuvant treatment for locally advanced gastric cancer after operation

Objective: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of tegafur, gimeracil and oteracil (S-l) 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 T_XN_1-3M₀ 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-l was orally administered twice every day of radiotherapy at a dose of 30 mg/(m²·d) (level IV, 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). Results: Twenty-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-l at 80 mg/(m²·d) (level IV) developing DLT. Conclusions: S-l with concurrent IMRT is safe and tolerable for locally advanced gastric cancer patients after operation. The MTD of S-l is 80 mg/(m²·d), which is recommended as the dose level in phase II and III studies, and S-l is orally administered twice every day of radiotherapy. The DLT are nausea, anorexia, and thrombocytopenia. (authors)