纳米白蛋白结合型紫杉醇联合替吉奥胶囊二线治疗进展期胃癌的效果

Phase Ⅰ trial of Nanoparticle paclitaxel plus TS-1 as second line chemotherapy in gastric cancer

目的拟确定胃癌患者应用纳米白蛋白结合型紫杉醇联合替吉奥胶囊作为二线治疗的最大耐受剂量(maximum tolerated dose,MTD)。方法纳米白蛋白结合型紫杉醇的剂量为100～125 mg/m^2,在第1天、第8天静脉注射,30分钟,替吉奥胶囊应连续口服14天,每天2次,然后休息1周,21天为1个周期。在第1个周期后评估剂量限制性毒性(dose limiting toxicity,DLT)。结果共19例患者参加了本试验。在纳米白蛋白结合型紫杉醇剂量为125 mg/m^2时,达到MTD:6例患者中的2例出现DLT。在接受剂量为100 mg/m^2的13例患者中,有1例患者出现发热性中性粒细胞减少症。最常见的血液系统不良事件是白细胞减少和中性粒细胞减少。结论作为胃癌的二线治疗,纳米白蛋白结合型紫杉醇的剂量水平为100 mg/m^2,第1天和第8天给药,联合替吉奥胶囊21天为一周期的方案耐受良好,并显示出令人鼓舞的疗效。

Objective To determine the maximum-tolerated dose （MTD） ofnab-paclitaxel plus TS-1 in patients with gastric cancer as second line therapy. Method The dose levels of nanoparticle paclitaxel were 100 - 125 mg/m2 on days 1, 8, given intravenously during 30 minutes of a 21-day cycle. TS-I should be given orally twice a day for 14 consecutive days, followed by a 1-week rest. Dose-limiting toxicities （DLT） were assessed after the first cycle. Result 19 patients were enrolled in the trial. At 125 mg/m2, the MTD was reached： 2 of 6 patients experienced DLT. Dose level of 100 mg/m2 was tolerated in a total of 12 patients with one DLT （febrile neutropenia）. Hematologic AEs were more common with leucopenia and neutropenia. Conclusion Nanoparticle paclitaxel 100 mg/m2 administered on days 1 and 8 of a 21-day cycle plus TS-1 is well tolerated and demonstrated encouraging activity in gastric cancer as second line therapy.