抗代谢类新药替吉奥片联合顺铂一线治疗晚期胃癌的临床研究

Clinical Study on Gimeracil and Oteracil Porassium Tablet Combined with Cisplatin in Chemotherapy of Advanced Gastric Cancer

目的评价海王替吉奥片联合顺铂一线治疗晚期胃癌的有效性、安全性。方法采用多中心、随机、开放,与顺铂联合氟尿嘧啶、亚叶酸钙的常规方案阳性对照研究,将177例患者按2:1分别入选试验组和对照组。试验组122例患者给予替吉奥片40mg/m2,2次/d,连续口服21d;顺铂60mg/m2,静脉滴注,于化疗第8天开始使用;每35天为1个周期,共2～6周期。对照组55例患者给予亚叶酸钙200mg/d,静脉滴注,于化疗第1～5天使用;氟尿嘧啶400mg/m2,静脉滴注4～6h,于化疗第1～5天使用;顺铂60mg/m2,静脉滴注,于化疗第1天开始使用;每28天为1个周期,共2～6周期。结果入组177例患者中,进入全分析集(FAS分析)试验组122例,对照组55例;符合方案集(PPS分析)试验组99例,对照组44例;安全性分析试验组122例,对照组55例。作为主要疗效指标的两组中位至肿瘤进展时间(mTTP),按FAS分析,试验组为21.0周(9.0～33.0周),对照组为9.0周(6.0～21.0周),差异有统计学意义(P=0.001);按PPS分析,试验组为22.0周(13.0～34.0周),对照组为12.5周(8.0～24.0周),差异有统计学意义(P=0.002)。不良反应主要是恶心呕吐(试验组63.93%,对照组67.27%)、腹泻(试验组19.67%,对照组7.27%)、便秘(试验组13.93%,对照组5.45%)、食欲不振(试验组1.64%,对照组5.45%)等消化道症状及脱发(试验组9.02%,对照组10.91%)、口腔炎(试验组5.74%,对照组7.27%);除试验组腹泻发生率相对高(P=0.0446)外,差异均无统计学意义(P>0.05)。其中Ⅲ或Ⅳ度临床症状不良反应主要为恶心呕吐(试验组8.20%,对照组10.91%)、腹泻(试验组4.10%,对照组1.82%),两组Ⅲ或Ⅳ度临床症状不良反应发生率比较,差异均无统计学意义(P>0.05)。结论国产海王替吉奥片联合顺铂用于晚期胃癌的一线治疗,疗效优于传统氟尿嘧啶联合顺铂方案,其耐受性好,使用方便,具有广阔的临床应用前景。

Objective To evaluate the efficacy and safety of Gimeracil and Oteracil Porassium tablet/cisplatin combination in the treatment of untreated advanced gastric cancer. Methods This study was a muhicenter, open, randomized and controlled clinical trial in subjects with advanced gastric cancer. In the test group, Gimeracil and Oteracil Porassium tablet was administered orally at 40 mg/m2, bid, from dl to d21, cisplatin was combined at 60 mg/m2 on d8, the treatment was repeated every 35 days. In the control group, CF was given at 200 mg/d, combined with Fluorouracil 400 mg/m2 from dl to d5, cisplatin was combined at 60 mg/m2 on dl, the treatment was repeated every 28 days. The patients were administerd 2-6 cycles of the first line chemotherapy. Results Of 177 cases, 177 were eligible for the analysis of side effects and 143 for the time to progress （TI＇P） as the main end point with PPS analysis. As the main end point, mean TIP was 22.0 weeks （13.0-34.0 weeks） in the test group, compared with 12.5 weeks （8.0-24.0 weeks） in the control group. There was significant difference between the two groups （P= 0.002 0）. The major adverse effects were nausea, vomting, diarrhea, there was no significant difference in Grade 3/4 adverse effects between the two groups （P〉0.05）. Conclusions Gimeracil and Oteracil Porassium tablet/cisplatin combination may have significant efficacy and tolerable toxicity for untreated advanced gastric cancer patients.