以紫杉醇为主的联合化疗方案治疗进展期胃癌随机对照研究

A Randomized Controlled Trail of Taxol-based Combination Regimens for Advanced Gastric Cancer

背景与目的:治疗晚期胃癌目前尚无公认的金标准方案。Ⅱ期临床研究发现紫杉醇类药物对胃癌有较好疗效。本研究对比亚叶酸钙/5-氟尿嘧啶(CF/5-FU)联合顺铂(DDP)、紫杉醇(Taxol)联合CF/5-FU、紫杉醇联合草酸铂(Oxaliplatin,OXA)方案治疗晚期胃癌的临床疗效与不良反应。方法:在福建省6家医院进行前瞻性、开放、随机对照研究,将符合入选标准的患者根据随机号码分入CF/5-FU+DDP、CF/5-FU+Taxol及Taxol+OXA3个组,用双周方案进行全身化疗(CF0.2g/m2,静滴,d1、2;5-FU2.0/m2,持续静脉滴注48h;DDP50mg/m2,静滴,d1;Taxol100mg/m2,静滴,d1;OXA100mg/m2,静滴,d1),配合每周一次DDP40mg/m2腹腔灌注化疗。按WHO标准评价疗效及不良反应。结果:2002年5月至2004年5月,入选180例合格病例,随机分入对照组(CF/5-FU+DDP组)60例,研究组120例(研究Ⅰ组:CF/5-FU+Taxol组及研究Ⅱ组:Taxol+OXA组各60例)。其中166例(92.22%)接受了至少2个周期的化疗,152例(84.44%)完成4个周期的化疗,103例(57.22%)完成了8个周期的化疗。166例可评价疗效,Taxol+OXA组疗效较对照组好(P<0.05)。在术前初治患者中,研究组Ⅰ组和Ⅱ组的疗效明显优于对照组(50.00%、80.00%与20.75%,P<0.05);在腹膜后淋巴结转移的患者中,研究组疗效明显优于对照组(65.96%、85.71%与36.36%,P<0.05);而在肝转移的患者中,研究组与对照组疗效近似(28.57%、39.13%与34.62%,P>0.05)。与对照组相比较,研究组患者中任何程度的恶心、呕吐、食欲差、口腔炎及肾功能减退发生率均较低,但骨髓抑制及末梢神经损害相对较严重,并有7例(5.88%)发生不同程度的过敏反应,其中严重过敏反应3例(2.52%)。无治疗相关死亡。结论:晚期胃癌患者采用含紫杉醇方案化疗虽然骨髓抑制较重,但总体疗效优于CF/5-FU+DDP方案,不良反应可以耐受。本研究推荐以紫杉醇为主的联合化疗方案作为晚期胃癌的一线化疗方案。

BACKGROUND ＆ OBJECTIVE： Standard chemotherapy for advanced gastric cancer remains undefined. Phase II trials show that taxol is effective in treating advanced gastric cancer. This multi-center prospective open randomized controlled study was to compare the efficacy of Taxol plus calcium folinate （CF）/5-fluorouracil （5-FU）, Taxol plus oxaliplatin （OXA）, and CF/5-FU plus cisplatin （DDP） on advanced gastric cancer, and analyze their toxicities. METHODS： Patients with measurable unresectable and/or metastatic gastric carcinoma were randomized into CF/5-FU＋DDP （control）, CF/5-FU＋Taxol, and Taxol＋OXA groups, and received up to 8 cycles of chemotherapy. Treatment efficacy and adverse events were evaluated according to WHO criteria. RESULTS： A total of 180 patients were enrolled from May 2002 to May 2004, and randomized into the 3 groups; each group contained 60 patients. Of the 180 patients, 14 received 2 cycles of chemotherapy, 49 received 4 cycles, and 103 received 8 cycles. Treatment outcomes of 166 cases were evaluable. The response rate （RR） of naive patients or the patients with retroperitoneal lymph node metastasis was significantly higher in CF/5-FU＋Taxol and Taxol＋OXA groups than in control group （50.00% and 80.00% vs. 20.75%, P〈0.05; 65.96% and 85.71% vs. 36.36%, P〈0.05）. But the RR of the patients with liver metastasis was similar among the 3 groups （28.57% and 39.13% vs. 34.62%, P〉0.05）. The occurrence rates of nausea/vomiting, anepithymia, stomatitis, and kidney damage were lower in study groups than in control group, but the occurrence rates of myelosuppression and peripheral nerve damage were higher in study groups than in control group. Allergic response occurred in 7 （5.88%） patients in study group, and 3 （2.52%） of them were serious. There was no treatment-related death. CONCLUSIONS： Despite its hematotoxicity, the treatment efficacy of Taxol-based combination regimens on advanced gastric cancer is better than that of CF/5-FU＋DDP regimen with tolerable toxicities. We recommend Taxol-based combination regimens as first-line regimens for advanced gastric cancer.