局部晚期胃癌术后辅助卡培他滨同步放疗的Ⅰ期临床研究

目的：探讨局部晚期胃癌术后辅助放疗同步卡培他滨的剂量限制性毒性（DLT）和最大耐受剂量（MTD）,并观察其副作用。方法：21例局部晚期胃癌术后经病理组织学检查证实为胃腺癌患者分为5组,行全程常规分割放射治疗,总剂量45Gy/25f;同期行化学治疗。卡培他滨初始剂量为1000mg/m2,用药剂量依次递增,2次/d,放疗期间周一至周五服用,周末暂停。组间递增剂量为200mg/m2,每个剂量组3例;如无DLT出现,该组进入下一剂量组,直至出现DLT;DLT的次一剂量组为MTD。结果：卡培他滨用药剂量为1800mg/m2时,出现DLT,表现为3级胃肠道反应和3度血液毒性;用药量在1600mg/m2时为MTD,表现为腹泻、恶心、呕吐、手足综合征、骨髓抑制和放射性皮炎。结论：胃癌术后同步放化疗卡培他滨的MTD为1600mg/m2,2次/d,放疗期间周一至周五服用,周末暂停。

Phase Ⅰ clinical trial of Capecitabine and concurrent radiotherapy as adjuvant therarpy for locally advanced gastric cancer

Objective： The purpose of the study was to determine the maximal tolerated dose（MTD） and the dose-limiting toxicity（DLT） of Capecitabine and concurrent radiotherapy as adjuvant treatment in patients with locally advanced gastric cancer. Methods： A total of 21 patients with advanced gastric adenocarcinoma after curative surgery were treated with radiotherapy to a total dose of 45Gy in 5 weeks. Capecitabine was administered at a dosage of 1 000 mg/m2（n=3） ,1 200 mg/m2（n=3） ,1 400 mg/m2（n=3） ,1 600 mg/m2（n=6） ,and 1 800 mg/m2（n=6） ,oral administration in twice daily on days 1-5,8-12,15-19,22-26,29-33. DLT was defined as Grade Ⅲ or Ⅳ hematologic and nonhematologic toxicity. Results： Grade Ⅰ-Ⅲ leukopenia,diarrhea,and nausea/vomiting were the most common toxic side effects,and most were Grade 1-2. DLTs were first observed in 2 of 3 patients at 1 600 mg/m2（1 of Grade Ⅲ diarrhea and 1 of Grade Ⅲ leukopenia） ,and then increase 3 patients in the group,but was not observed in the same group.Then enter next 6 patients 1800mg/m2 group.At 1800 mg/m2,DLTs were observed in 4 of 6 patients（2 of Grade Ⅲ leukopeniaand 1 of Grade Ⅲ nausea/vomiting and 1 of Grade Ⅲ diarrhea） . toxicities included myelosupression,nausea,vomiting and hand-foot syndrome.Conclusions： Diarrhea were the most common dose-limiting toxicity（DLT） . MTD of Capecitabine in this experiment was 1600mg/m2,bid,d 1-5,8-12,15-19,22-26,29-33.