局部晚期直肠癌重组人血管内皮抑制素联合新辅助放化疗临床观察

Clinical observation of recombinant human endostatin combined with neoadjuvant chemoradiotherapy to cure patients with local advanced rectal cancer

目的新辅助放化疗+手术已成为局部晚期直肠癌的标准治疗。血管内皮生长因子(vascular endothelial growth factor,VEGF)高表达可能是放疗不敏感的重要原因,重组血管内皮抑制素为抗血管生成药物,可提高多种恶性肿瘤放化疗敏感性。本研究观察重组血管内皮抑制素能否提高新辅助放化疗对局部晚期直肠癌的疗效,并观察其副作用,探讨VEGF表达与重组血管内皮抑制素作用的关系。方法选取2009-01-01-2012-12-31滨州医学院附属医院收治的局部晚期直肠癌患者76例,随机分为实验组40例和对照组36例,免疫组化SP法检测组织中VEGF表达情况。实验组采用重组血管内皮抑制素+新辅助放化疗+手术的方法,对照组采用新辅助放化疗+手术的方法。放疗结束后磁共振成像(magnetic resonance imaging,MRI)及腔内超声评价近期疗效,休息6周后行手术治疗。结果两组患者均完成治疗。实验组完全缓解(complete response,CR)8例、部分缓解(partial response,PR)29例,有效率为92.5%。对照组CR 3例、PR 20例,有效率为63.9%。两组间根治性切除率分别为95.0%和77.8%,两组间2年局部复发率分别为7.5%和25.0%。两组近期有效率(χ~2=9.932,P=0.002)、根治性切除率(χ~2=9.571,P=0.002)、2年局部复发率(χ~2=14.821,P<0.001)比较差异有统计学意义。而其骨髓抑制(χ~2=0.009,P=0.923)、胃肠道反应(χ~2=0.025,P=0.875)、肝毒性(χ~2=0.247,P=0.619)等主要毒副作用比较差异无统计学意义。进一步亚组分析显示,VEGF高表达患者两组近期有效率(χ~2=11.075,P=0.001)、根治性切除率(χ~2=12.325,P<0.001)、2年局部复发率(χ~2=8.956,P=0.003)比较差异有统计学意义。结论局部晚期直肠癌中,重组血管内皮抑制素可以提高新辅助放化疗的近期疗效、降低局部复发率,不增加副作用。在VEGF高表达患者中疗效更显著。

OBJECTIVE Neoadjuvant chemoradiotherapy plus surgery has become the standard treatment for locally advanced rectal cancer.The high expression of vascular endothelial growth factor（VEGF）may be an important cause of poor sensitivity to radiochemotherapy.Recombinant endostatin can improve the sensitivity of multiple malignant tumors to radiotherapy and chemotherapy as anti angiogenic drug.The aim of this study is to explore the outcome and safety Endu combined with neoadjuvant chemoradiotherapy in treating local advanced rectal cancerand and to investigate the relationship between VEGF expression and the effect of endostatin.METHODS 76 patients with locally advanced rectal cancer treated in Binzhou Medical University Hospital from 2009-01-01 to 2012-12-31 were enrolled this study.The patients were randomly divided into two groups：experiment group（n=40）and control group（n=36）.The expression of VEGF in tissue was detected by immunohistochemistry SP method.In control group,the patients received neoadjuvant chemoradiotherapy.In experiment group,treatment regimen was the same as in control group except that recombinant endostatin was used.Recent curative effect was evaluated by MRI and Transrectal Ultrasonography.The surgical resection was performed six weeks after chemoradiotherapy.RESULTS The patients in both groups completed the treatments.Complete response（CR）occurred in 8 cases,partial response（PR）in 29 cases,and the efficiency reached 92.5% in experiment group.In control group,CR developed in 3 cases,PR in 20 cases,and effective rate was 63.9%.The radical resection rate in the two groups were 95.0%and 77.8%,respectively.The local recurrence rate in 2 years between the two groups were7.5% and 25.0%.The effective rate（χ^2=9.932,P=0.002）,local radical resection rate（χ^2=9.571,P=0.002）and local recurrence rate in 2 years（χ^2=14.821,P〈0.001）were statistically different between the two groups.But the main side effects,such as myelosuppression（χ^2=0.009,P=0.923）,gastrointestinal reaction（χ^2=0.025,P=0.875）,hepatotoxicity（χ~2=0.247,P=0.619）and so on were not statistically significant.Further subgroup analysis showed that the effective rate（χ^2=11.075,P=0.001）,local radical resection rate（χ^2=12.325,P〈0.001）and local recurrence rate in2 years（χ^2=8.956,P=0.003）were statistically different between the two groups in the high expression of VEGF.CONCLUSIONS Recombinant endostatin can improve the recent curative effect of neoadjuvant chemoradiotherapy and reduce the local recurrence rate,without increasing side effect in patients with local advanced rectal cancer.The effect is more significant in the patients with high expression of VEGF.