卡培他滨与氟尿嘧啶/亚叶酸钙联合奥沙利铂治疗晚期胃癌的随机对照临床研究

A randomized clinical study of capecitabine plus oxaliplatin compared with fluorouracil/leucovorin plus oxaliplatin in the treatment of advanced gastric cancer

背景与目的：目前对进展期及转移性胃癌还没有标准的化疗方案,而且缺乏有效率高、毒副反应小、安全的化疗方案.毒副反应是晚期胃癌化疗的限制性因素,影响患者的生活质量.本研究观察及比较两种常用化疗方案卡培他滨联合奥沙利铂方案（XELOX）与氟尿嘧啶/亚叶酸钙联合奥沙利铂方案（FOLFOX4）治疗晚期胃癌的临床疗效及毒副反应,以期取得在较佳疗效保证的同时,毒副反应小,耐受性更好的效果.方法：48例晚期胃癌患者随机分成两组,XELOX组与FOLFOX4组.XELOX组25例,用卡培他滨联合奥沙利铂方案化疗,卡培他滨1000 mg/m^2,口服,2次/日,第1～14天;奥沙利铂130 mg/m^2,静脉点滴,第l天;2l d为1个周期.FOLFOX4组23例,用氟尿嘧啶/亚叶酸钙联合奥沙利铂方案化疗,奥沙利铂85 mg/m^2,静脉点滴,第1天;亚叶酸钙200 mg/m^2,静滴2 h后予氟尿嘧啶400 mg/m^2,推注,后续600 mg/m^2持续静滴22 h,第1、2天;每2周重复,4周为1周期.两组均治疗2周期以上.按wH0标准评价客观疗效和毒副反应.结果：入组48例均可评价疗效,XELOX组有效率56.0%,中位TTP 5.8个月,MST 10个月,FOLFOX4组有效率47.8%,中位TTP 5.7个月,MST 9.8个月.两组近期有效率差异无显著性.毒副反应比较,手足综合征以：XELOX组显著（P＜0.05）,Ⅲ/Ⅳ级恶心呕吐发生率以FOLFOX4.组显著（P＜0.05）,其余毒副反应除腹泻外发生率以FOIFOX4组稍高,但差异无显著性.结论：XELOX方案与FOLFOX4方案治疗晚期胃癌疗效确切,毒副反应能耐受.两组近期疗效相似,毒副反应以XELOX组更易耐受,尤其对一般情况欠佳及老年的患者耐受性好.

Background and purpose： There is still no standard chemotherapy regimen for advanced and metastatic gastric cancer , and the regimen with high efficacy and safety are scare . Severe toxicities are considered to be limiting factors and influence the quality of life in the patients with advanced gastric cancer. The purpose of this study was to evaluate the efficacy and toxicity of capecitabine plus oxaliplatin regimen （XELOX） versus fluorouracil/leucovorin （LV5FU2） plus oxaliplatin regimen （FOLFOX4） in the treatment of advanced gastric cancer and try to find the regimen more tolerable without the deterioration of treatment response. Methods： 48 cases with advanced gastric cancer were enrolled into this study, 25 patients and 23 patients were randomly divided into XELOX group and FOLFOX4 group respectively. XELOX group was treated with capecitabine 1 000 mg/（m^2·d）, po, bid, d 1-14; oxaliplatin 130 mg/（m^2·d）, ivgtt, d 1. FOLFOX4 group was treated with oxaliplatin 85 mg/（ m2. d）, ivgtt, d 1 ; LV 200 mg/m^2 ivgtt 2 hr followed by 5-Fu 400 mg/m^2 （bolus） and 5-Fu 600 mg/m^2（22 hr-coutinous infusion）. XELOX regimen was repeated every 3 weeks for one cycle, FOLFOX4 regimen was repeated every 2 weeks, 4 weeks for one cycle. All patients received two cycles of chemotherapy at least. The efficacy and toxicity were evaluated according to WHO standard. Results： All 48 cases were available for objective response. The overall response rate was 56% （ CR 1, PR 13） in XELOX group of 25 cases and 47.8% （ CR 1, PR 10） in FOLFOX4 group of 23 cases. The difference in response rate was not statistically significant between the two groups （P 〉 0.05）. The median time to progression （mTFP） was 5.8 months in XELOX group and 5.7 months in FOLFOX4 group. The median survival time （MST） was 10.0 months in XELOX group and 9.8 months in FOLFOX4 group, The toxicities were well tolerated, The incidence of grade Ⅲ ＋ Ⅳ nausea and vomiting was significantly lower in XELOX group than in FOLFOX4 group （P 〈 0.05） but hand and foot syndrome in XELOX group were more obvious than in FOLFOX4 group （P 〈 0.05）, Incidence of other side effects in FOLFOX4 group was higher than that of those in XELOX group except for diarrhea, but no significance existed （P 〉 0.05）. Conclusions： Both of the two regimens were feasible, well tolerated and effective in treatment of advanced gastric cancer. XELOX regimen may be safer than FOLFOX4 regimen, especially in elderly patients or patients with ECOG PS of 1 to 2.