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

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

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。

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.