Phase Ⅰ study of postoperative radiotherapy combined with capecitabine for gastric cancer

摘要： AIM:To determine the maximum tolerated dose(MTD)and dose-limiting toxicity(DLT)of capecitabine combined with postoperative radiotherapy for gastric cancer.METHODS:We enrolled patients with any T stage and node-positive gastroesophageal or gastric adenocarcinoma after complete resection with negative margins(R0)or microscopic(R1)or macroscopic(R2)resection.Intensity modulated radiotherapy(IMRT)using a fiveto-seven-field,coplanar,sliding window technique was delivered to the tumor bed(T4b),anastomosis site,duodenal stump and regional lymph nodes(LNs)to a total dose of 45 Gy(1.8 Gy/fraction,5 d/wk).Patients with R1 or R2 resection received 10.8 Gy as a boost.Capecitabine was administered twice daily on every radiotherapy treatment day in a dose-escalation schedule (mg/m2)of 625(levelⅠ,n=6),700(levelⅡ,n=6),800(levelⅢ,n=6),900(levelⅣ,n=0)and 1000(levelⅤ,n=0).DLT was defined as grade 4 leukopenia or neutropenia,grade 3-4 thrombocytopenia or anemia and grade 3-4 non-hematological toxicity.RESULTS:Between October 2007 and August 2009,18 patients(12 men,6 women;median age,54 years)were enrolled in the study.The median number of positive LNs was 6,and total number of resected LNs was19.Twelve patients underwent R0 resection(66.7%).Fifteen patients received adjuvant chemotherapy under the leucovorin,fluorouracil and oxaliplatin(FOLFOX4)regimen.Six patients each were enrolled at dose levelsⅠ,ⅡandⅢ.Grade 1-3 leukopenia(16 patients,88.9%),anorexia(15,83.3%)and nausea(15,83.3%)were the most common toxicities.Grade 3 anorexia/nausea and grade 4 vomiting occurred in one level-Ⅰpatient.Grade 3 anorexia and nausea occurred in one level-Ⅱpatient.One level-Ⅲpatient developed grade 4neutropenia,while another developed grade 3 radiation esophagitis.No abnormal liver or renal function examinations were observed.Three patients did not finish chemoradiotherapy because of DLTs and two without DLTs received sequential boosts(total dose,55.8 Gy).CONCLUSION:The MTD of capecitabine was 800 mg/m2twice daily concurrent with IMRT for gastric cancer after surgery.The DLTs were anorexia/nausea,vomiting,neutropenia and radiation esophagitis. ... （共7頁）