紫杉醇每周方案联合氟特嗪胶囊与氟尿嘧啶治疗晚期胃癌的Ⅱ期前瞻性随机对照研究

A phase Ⅱ prospective randomized controlled trial of weekly paclitaxel combined with S-1 orfluorouracil for advanced gastric carcino_ m_ _a__

目的评价紫杉醇每周方案联合氟特嗪胶囊与氟尿嘧啶（5-Fu）一线治疗晚期胃癌的临床疗效和安全性。方法240例未经治疗的晚期胃癌患者，随机分为试验组和对照组，每组各120例患者。试验组采用紫杉醇联合氟特嗪胶囊，紫杉醇60mg／m^2，静脉滴注，第1、8、15天；氟特嗪胶囊80-120mg／d，口服，第1-14天。对照组采用紫杉醇联合5-Fu，5-Fu500mg／m^2，持续静脉输注，第1-5天；亚叶酸钙20mg／m^2，静脉滴注，第1-5天。两组均为每28天重复。结果240例患者中，228例患者进入全分析集，192例患者可评价疗效，其中试验组100例，对照组92例。试验组和对照组的客观缓解率分别为50．0％和28．3％（P=0．002），疾病控制率分别为82．0％和70．7％（P=0．064）。试验组患者的中位无进展生存时间为153d，对照组为129d（P=0．006）。试验组Ⅲ-Ⅳ级骨髓抑制发生率高于对照组，但两组发热发生率差异无统计学意义（P=0．439）。结论口服氟特嗪胶囊可以替代静脉输注5-Fu，紫杉醇每周方案联合氟特嗪疗效较高，安全性良好。

Objective To evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma. Methods Two hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-I, while those in the control ann received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m2 by intravenous infusion, dayl, 8, 15 ;S-1 80-120 mg/day given by oral administration, day 1-14. The regimen of control arm was fluorouracil 500 mg/m2 by intravenous infusion continuously, dayl-5;CF 20 mg/m2 by intravenous infusion, dayl-5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed. Results Two hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set （experimental arm 100 patients, control arm 92 patients）. The overall response rates of experimental and control arms were 50.0% and 28.3% （P = 0. 002） , and the disease control rates were 82.0% and 70.7% （ P = 0. 064 ）, respectively. The primaD endpoints of experimental arm were non-inferior to that of the control ann. The secondary endpoint of experimental arm in terms ofmedian progression free survival was significantly better than that of control arm （5 months versus 4 months, P = O. 006）. The experimental arm had a higher incidence of grade Ⅲ-Ⅳ bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different. Conclusions Oral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.