紫杉醇联合FOLFOX4方案新辅助化疗在进展期胃癌中的临床应用

目的 评价紫杉醇联合FOLFOX4方案（氟尿嘧啶、甲酰四氢叶酸和奥沙利铂）新辅助化疗治疗进展期胃癌的临床疗效及不良反应.方法 应用前瞻性随机对照的方法将cTNM分期为Ⅲ或Ⅳ期（M0） 的胃癌患者78例,按入组顺序根据随机数字表法随机分配到试验组（39例）和对照组（39例）.试验组给予紫杉醇联合FOLFOX4方案的新辅助化疗,每2周为1周期,3周期后采用RECIST标准评价临床疗效,2～4周后手术,术后给予原方案化疗3周期.若术前评效为疾病进展（PD）者,术后改为ECF方案（表阿霉素、顺铂和氟尿嘧啶）化疗.对照组确诊后2周内手术.术后给予6周期紫杉醇联合FOLFOX4方案的辅助化疗.结果 试验组紫杉醇联合FOLFOX4方案新辅助化疗的临床有效率为66.7%,R0切除率（82.1%）明显高于对照组（59.0%）（P＝0.025）,淋巴结转移数目[（3.23±2.80）枚]明显少于对照组[（5.79±2.69）枚]（P＝0.001）,术后并发症发生率（5.1%和2.6%）及淋巴结清扫数目[（19.69±2.95）枚和（20.59±3.22）枚]两组差异均无统计学意义（P＞0.05）.试验组和对照组术后中位生存期分别为（27.10±2.32）个月和（18.20±1.30）个月（P＝0.006）.Cox回归多因素分析显示,肿瘤分化程度、R0切除、淋巴结转移均是影响预后的独立因素.化疗不良反应主要为血液学及末梢神经毒性,患者均可耐受,两组化疗不良反应差异无统计学意义（P＞0.05）.结论 紫杉醇联合FOLFOX4方案新辅助化疗有效率高,患者耐受性和依从性好,可提高进展期胃癌患者的R0切除率、降低淋巴结转移率,提高生存率.

A clinical study of paclitaxel combined with FOLFOX4 regimen as neoadjuvant chemotherapy for advanced gastric cancer

Objective To evaluate the clinical efficacy and the toxicity of neoadjuvant chemotherapy with paclitaxel and FOLFOX4 （5-fluorouracil/leucovorin combined and oxaliplatin） regimen for advanced gastric cancer. Methods Seventy-eight patients with cTNM stage Ⅲ or Ⅳ（M0） gastric cancer were enrolled and 39 were randomized into the treatment arm（n=39, paclitaxel combined with FOLFOX4 regimen neoadjuvant chemotherapy every two weeks in each cycle） and control group（n=39）. Clinical response was evaluated with RECIST criteria after 3 cycles. Patients in experimental group received surgery after 2-4 weeks and postoperative chemotherapy of 3 cycles of the original regimen. When disease progressed, postoperative chemotherapy regimen was changed into ECF regimen. The control group of 39 patients received surgery within 2 weeks and postoperative chemotherapy of 6 cycles of paclitaxel combined with FOLFOX4 regimen. Results The clinical response rate was 66.7% in the treatment arm. The R0 resection rate（59.0%） was significantly higher than that in the control group （P=0.025） and the number of lymph node metastasis in the treatment arm（3.23±2.80） was significantly lower than that in the control group（5.79±2.69, P=0.001）. There were no significant differences in postoperative complication rate （5.1% vs. 2.6%） and the number of lymph node dissection （19.69±2.95 vs. 20.59±3.22） between the two groups （P〉0.05）. The median survival time and 2-year survival rate in the treatment arm[（27.10±2.32） months and 59.0%] was significantly higher than that in the control group[（18.20±1.30） months and 28.2%]（P=0.001,P=0.006）. Cox regression multivariable analysis showed that tumor differentiation, R0 resection, lymph node metastasis were independent prognostic factors. Adverse reaction of chemotherapy, mainly hematological adverse reactions, and peripheral nerve toxicity, were tolerable. No significant differences were noted between the two groups in adverse reactions（P〉0.05）. Conclusions The efficacy of paclitaxel combined with FOLFOX4 as neoadjuvant chemotherapy is high. Patients tolerance and compliance are satisfactory. It can improve in patients with advanced gastric cancer the R0 resection rate, reduce lymph node metastasis and improve survival.