摘要目的 探讨Ⅱ、Ⅲ期直肠癌术后,应用奥沙利铂(oxaliplatin,L-OHP)、5-氟尿嘧啶(5-Fu)、亚叶酸钙(LV)进行同步放疗的剂量限制性毒性(dose limiting toxicity,DLT)和最大耐受剂量(maximal tolerated dose,MTD),并观察其毒副作用.方法 将Ⅱ、Ⅲ期直肠癌术后、经病理证实为直肠腺癌的21例患者分为5组(每组3例3组,每组6例2组),行全程常规分割放疗,总剂量50 Gy/25 f;同期进行化疗,5-Fu固定在恒定的剂量(300 mg/m2 2 h内静脉滴注,然后500 ms/m2 22 h内静脉滴注,d1,d2).LV剂量为200 mg/m2静脉滴注2 h,d1,d2.L-OHP的用药剂量则逐渐增加,起始剂量组(3例)为45 mg/m2,静脉滴注,d1;组递增剂量为10 mg/m2,如无DLT出现,进入下一剂量组,直至出现DLT;DLT的次一剂量组为MTD.结果 DLT为3度放射性直肠炎和3度血液毒性,发生于L-OHP 85 mg/m2组剂量水平;次一剂量L-OHP 75 mg/m2为MTD.主要毒性反应为放射性直肠炎、白细胞减少、厌食和放射性皮炎.结论 直肠癌同步放化疗L-OHP联合5-Fu、LV方案中L-OHP的最大耐受剂量为75 mg/m2.

abstractsObjectives To determine maximal tolerated dose(MTD)and dose-limiting toxicity (DLT) of oxaliplatin(L-OHP)when combined with constant dosing of 5-Fu、Lv and concurrent radiotherapy in postoperative patients with rectal cancer.Methods A total of 21 patients with stage Ⅱ or Ⅲ rectal adenocarcinoma after curative surgery were treated with radiotherapy to a total dose of 50 Gy in 5 weeks.L-OHP was administered at a dosge of 45 mg/m2(n=3),55 mg/m2(n=3),65 mg/m2(n=3),75 mg/m2(n=6),and 85 mg/m2(n=6)once a week for 2 weeks(first cycle)followed by a second cycle after a 14-day break.5-Fu and LV at a fixed dose of 5-Fu 300 mg/m2 ivdrip for 2 h,then 500 mg/m2 ivdrip within 22 h,d1,d2.LV 200 mg/m2 ivdrip 2 h d1,d2.DLT was defined as grade Ⅲ or Ⅳ hematologic and nonhenmologic toxicity. Results Grade Ⅰ-Ⅲ leukopenia,diarrhea,and nausea/vomiting were the most common toxic side effects.and most were of grade 1-2.DLT was first observed in 2 of 3 patients at 75 mg/m2(1 of grade Ⅲ diarrhea and 1 of grade Ⅲ leukopenia).L-OHP at dosage of 85 mg/m2 caused DLT in 4 of 6 patients(2 of grade Ⅲ leukopenia and 1 of grade Ⅲ diarrhea and 1 of grade Ⅲ diarrhea).Conclusions Diarrhea was the most common dose-limiting toxicity(DLT).Tlle maximal tolerated dose(MTD)of L-OHP in this setting was 75 mg/m2 which was comparable to the maximal tolerated dose of L-OHP seen in the neoadjuvant setting.