XELOX和FOLFOX4新辅助化疗方案对不能手术切除的局部进展期胃癌的疗效比较

Comparison of the efficacy of XELOX and FOLFOX4 in the treatment of locally advanced unresectable gastric cancer

目的 比较XELOX和FOLFOX4两种新辅助化疗方案对不能手术切除的局部进展期胃癌患者的疗效.方法 前瞻性分析2006年7月至2009年10月山东大学附属省立医院收治的72例胃癌患者的临床资料.对由多学科协作小组评定不能手术切除的局部进展期胃癌患者,按照随机数字表法分为XELOX组（36例）和FOLFOX4组（失访3例,最终纳入本研究33例）.两组患者分别采用XELOX方案和FOLFOX4方案化疗6周.6周后根据复查结果由多学科协作小组评估疗效,对于完全缓解和部分缓解的患者施行手术切除并采用流式细胞仪检测细胞周期.率的比较采用Pearson x2检验;胃癌细胞周期各指数先采用Levene检验进行方差齐性检验,方差不齐采用t′检验,方差齐采用t检验.结果 XELOX组和FOLFOX4组的有效率分别为53%（19/36）和52%（17/33）,两组比较,差异无统计学意义（x2=0.01,P＞0.05）.XELOX组和FOLFOX4组中患者恶心呕吐、静脉炎、手足综合征的发生率分别为25%（9/36）、6%（2/36）、19%（7/36）和55%（18/33）、39%（13/33）、3%（1/33）,两组比较,差异有统计学意义（x2=6.31,11.59,4.53,P＜0.05）.XELOX组化疗有效的19例患者和FOLFOX4组化疗有效的17例患者接受手术切除,术后未发生吻合口漏、大出血等严重并发症.新辅助化疗后,XELOX组胃癌细胞的S期细胞比率（SPF）、增殖指数（PI）、G2/M分别为5.89%±0.79%、9.22%±1.99%、5.19%±1.66%,低于新辅助化疗前的6.76%±1.21%、10.44%±2.12%、6.04%±0.57%,而新辅助化疗后G0/G1为90.39%±4.78%,高于新辅助化疗前的87.54%±6.34%（x2=3.61,2.52,2.15,2.91,P＜0.05）;FOLFOX4组新辅助化疗后的SPF、PI、G2/M分别为6.09%±0.96%、10.65%±2.47%、4.88%±0.87%,低于新辅助化疗前的7.15%±1.45%、11.87%±2.33%、5.67%±1.03%,而新辅助化疗后G0/G1为91.45%±5.22%,高于新辅助化疗前的88.01%±4.23%（x2=3.50,2.06,3.37,2.94,P＜0.05）.新辅助化疗后两组PI值比较,差异有统计学意义（x2=2.66,P＜0.05）.结论 XELOX和FOLFOX4两种新辅助化疗方案对不能手术切除的局部进展期胃癌患者安全、有效,对胃癌细胞的增殖抑制明显;XELOX方案比FOLFOX4方案更为有效.

Objective To compare the efficacy of XELOX and FOLFOX4 in the treatment of locally advanced unresectable gastric cancer. Methods The clinical data of 72 patients with gastric cancer who were admitted to the Shandong Provincial Hospital from July 2006 to October 2009 were prospectively analyzed. Of all the patients, 3 lost follow-up, and 69 patients with locally advanced unresectable gastric cancer were randomly divided into XELOX group （ n = 36 ） and FOLFOX4 group （ n = 33 ） according to the random number table.All patients received chemotherapy for six weeks. The efficacy of the two regimens were evaluated by the multidiscipline team six weeks later. The cell cycle of patients with complete or partial remission and received surgical treatment was detected by flow cytometry. All data were analyzed using the Pearson chi-square test, Levene test or t test. Results The curative rates of XELOX and FOLFOX4 were 53% （19/36） and 52% （17/33）, respectively,with no significant difference between the two groups （ x2= 0. 01 , P 〉 0. 05 ）. The incidences of nausea and vomiting, phlebitis and hand-foot syndrome were 25% （9/36）, 6% （2/36） and 19% （7/36） in the xELOX group, and 55% （ 18/33）, 39% （13/33） and 3% （1/33） in the FOLFOX4 group, respectively, with significant difference between the two groups （ x2 = 6.31, 11.59, 4.53, P 〈 0.05 ）. Nineteen patients in the XELOX group and 17 patients in the FOLFOX4 group received surgical resection of the gastric cancer, and no complications such as anastomotic leakage and hemorrhage occurred postoperatively. In the XELOX group, the s-phase fraction （SPF）,proliferation index （PI） and G2/M of the gastric cancer cells were 5.89% ± 0.79%, 9.22% ± 1.99% and 5.19% ± 1. 66% after neoadjuvant chemotherapy, which were significantly lower than 6.76% ± 1.21%, 10.44% ±2.12% and 6. 04% ± 0. 57% before neoadjuvant chemotherapy, while the ratio of gastric cancer cells in the G0/G1 phase after neoadjuvant chemotherapy was 90.39% ±4.78%, which was significantly higher than 87.54%±6.34% before neoadjuvant chemotherapy （x2 =3.61, 2.52, 2. 15, 2.91, P 〈0.05）. In the FOLFOX4group, the SPF, PI and G2/M of the gastric cancer cells were 6.09% ± 0.96%, 10.65 % ± 2.47% and 4.88% ±0.87% after neoadjuvant chemotherapy, which were significantly lower than 7.15% ± 1.45%, 11.87% ± 2.33%and 5.67% ± 1.03% before neoadjuvant chemotherapy, while the ratio of gastric cancer cells in the G0/G1 phase after neoadjuvant chemotherapy was 91.45% ± 5.22%, which was significantly higher than 88.01% ± 4.23%before neoadjuvant chemotherapy （ x2 = 3.50, 2.06, 3.37, 2.94, P 〈 0.05 ）. There was a significant difference in PI between XELOX group and FOLFOX4 group after neoadjuvant chemotherapy （ x2 = 2.66, P 〈 0.05 ）.Conclusions XELOX and FOLFOX4 are safe and effective in the treatment of locally advanced unresectable gastric cancer, and they can significantly restrain the proliferation of gastric cancer cells. XELOX regimen is more effective than FOLFOX4 regimen.