【作者】 王娜；

【导师】 高亚杰；

【作者基本信息】 大连医科大学 ， 肿瘤学， 2017， 硕士

【摘要】 背景与目的胰腺癌高度恶性,早期患者可手术治愈。但是多数胰腺癌患者初诊时便已进入晚期阶段,因此治疗手段主要是姑息缓解治疗。放化疗疗效有限,毒副性大,患者生活质量明显下降,因此探讨更为有效且毒副作用小的治疗方案势在必行。随着对胰腺癌生物学行为的深入了解,研究发现胰腺癌是一个多基因突变的疾病,这为胰腺癌靶向治疗的靶点选择提供了多种可能。相比细胞毒类药物,靶向药物具有疗效好、不良反应小的特点。本研究旨在探讨晚期胰腺癌患者采用尼妥珠单抗联合化疗的临床疗效。方法1.回顾性收集2013年1月-2016年1月在大连医科大学附属第一医院、大连市中心医院、中国人民解放军第210医院应用尼妥珠单抗联合吉西他滨(gemcitabine,GEM)±替吉奥(tiggio,S-1)方案治疗的晚期胰腺癌患者14例(观察组),同期对比20例应用GEM±S-1化疗的晚期胰腺癌患者(对照组)。比较两组的临床受益反应、近期疗效、生存期、毒副反应。2.采用SPSS 17.0软件进行数据分析,计数资料的描述采用率和百分比;组别比较:计数资料采用Fisher确切概率检验;计量资料方差齐时采用t检验,方差不齐时采用t’检验(若为非正态分布,则采用Wilcoxon秩和检验);等级资料采用秩和检验;生存分析采用Kaplan-Meier法,组别比较采用Log-Rank方法。以α=0.05为检验性水准,P<0.05为差异有统计学意义。结果1.观察组患者临床受益反应显著高于对照组:疼痛改善、体力状况提高、体重增加发生率比较(78.6%vs15%、64.3%vs10%、42.9%vs10%),差异具有统计学意义(P<0.05);2.观察组和对照组客观有效率无统计学差异(28.6%vs5%,P>0.05),而疾病控制率分别为85.7%vs30%,差异具有统计学意义(P<0.05);肿瘤标志物癌胚抗原(carcino-embryonic antigen,CEA)和糖链抗原 19-9(carbohydrate antigen 19-9,CA19-9)下降例数分别有9例、5例(64.3%vs25%),有统计学差异(P<0.05);3.观察组和对照组的中位生存期分别为10.9个月和6.9个月,差异具有统计学意义(P<0.05),1年生存率分别为35.7%(5/14)、10%(2/20),差异无统计学意义(P>0.05);4.毒性反应主要表现为骨髓抑制、胃肠道反应、肝肾功损伤,观察组和对照组均无患者出现Ⅳ度毒副反应。血液毒性方面,白细胞减少、中性粒细胞减少、血小板减少、贫血发生率分别为:42.86%vs60%、50%vs80%、14.29%vs45%、21.43%vs50%,差异无统计学意义(P>0.05);胃肠道反应方面主要是恶心、呕吐,两组发生率分别为71.43%和80%,差异无统计学意义(P>0.05);肝肾功损伤发生率分别为21.43%和40%,差异无统计学意义(P>0.05)。结果提示加入尼妥珠单抗不会增加患者化疗不良反应的发生率。结论对晚期胰腺癌患者采用尼妥珠单抗联合化疗方案治疗,可以提高近期疗效,为患者带来显著临床受益反应,且不增加化疗不良反应发生率,对患者的生活质量影响较小。尼妥珠单抗联合化疗对晚期胰腺癌患者的临床疗效优于单纯化疗,其疗效和安全性值得肯定,有望成为晚期胰腺癌患者的有效选择之一。更多还原

【Abstract】 Background and ObjectivePancreatic cancer is one of the malignant digestive system tumors with higher levels.Surgical excision might be a good treatment choice and offer hope for long-term survival for early pancreatic cancer.However,early pancreatic cancer is rarely discovered,and most patients are diagnosed at the advanced stage.Therefore,the treatment is mainly palliative care.The clinical efficacy of traditional radiotherapy or chemotherapy is limited,even accompanied by serious side effects.The living quality of patients decreased significantly.Therefore,to explore more effective and less side effects of treatment is imperative.With the deep understanding of the biological characteristic of pancreatic cancer,the study found that there is a multi-gene mutation in pancreatic cancer,and it provides a variety of possible targets for the therapy of pancreatic cancer.Compared with cytotoxic drugs,targeted drugs have a better effect and less adverse effects.The aim of this study was to investigate the clinical efficacy of nimotuzumab combined with chemotherapy in advanced pancreatic cancer patients.Methods and patients1.Retrospectively analyzed the clinical data of 34 cases with advanced pancreatic cancer diagnosed by the First Affiliated Hospital of Da Lian Medical University,Da Lian City Central Hospital and Chinese People’s Liberation Army 210 Hospital in 2013.01-2016.01.According to the treatment,patients were divided into two groups:observation group which included 14 cases was treated with nimotuzumab combined with gemcitabine(GEM)and tiggio(S-1),or nimotuzumab combined with gemcitabine,compared with 20 cases of gemcitabine and tiggio chemotherapy,or gemcitabine(control group)in advanced pancreatic cancer during the same period.The aim of this study was to compare of the two groups of clinical benefit response,recent efficacy,clinical benefit response,survival time and toxic side effects.2.All dates were analyzed by the software SPSS 17.0.The count data was described by rate and percentage,the comparison of the count data used by Fisher’s exact probability test,the measurement data used t test,if the variance is not using t’test(if for non-normal distribution,using Wilcoxon rank and inspection),and the grade data used rank sum.The Kaplan-Meier and Log-Rank methods were used for testing and survival analysis.According to α = 0.05 for the test level,P values less than 0.05 were considered statistically significant.Results1.The clinical benefit response was significantly higher in the observation group than in the control group:the rate of pain relief,physical condition improvement and weight gain were 78.6%vsl5%,64.3%vs10%,42.9%vs10%,the difference was statistically significant(P<0.05);2.The overall response rate of the observation group and the control group was no significant difference(28.6%vs5%,P>0.05),while the control rate of disease was 85.7%vs30%,the difference was statistically significant(P<0.05);the incidence of tumor markers including carcino-embryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)decreased was 64.3%vs25%,the difference was statistically significant(P<0.05);3.The median overall survival was 10.9 months vs6.9 months,and the difference was statistically significant(P<0.05),The 1-year survival rates were 35.7%(5/14)and 10%(2/20)respectively,the difference was no significant(P>0.05);4.The toxicity mainly manifested as myelosuppression,gastrointestinal reactions,liver and kidney injury,and the whole group had no patients with grade Ⅳ toxicity.The incidence of leukopenia,neutropenia,thrombocytopenia,anemia was 42.86%vs60%,50.00%vs80%,14.29%vs45%,21.43%vs50%in blood toxicity,and the difference was not statistically significant(P>0.05).The incidence of gastrointestinal reactions in the observation group and the control group was 71.43%and80%,respectively.There was no significant difference between the two groups(P>0.05).The incidence of liver and kidney injury in the observation group and the control group was 21.43%and40%respectively.There was no significant difference between the two groups(P>0.05).These data suggested that the addition of nimotuzumab did not increase the incidence rate of adverse reactions in patients with chemotherapy.ConclusionsThe treatment of patients with advanced pancreatic cancer with nimotuzumab combined with chemotherapy can bring significant clinical benefit response and improve the short-term curative effect without increasing the incidence of adverse reactions with less impaction on the quality of life for patients.In the treatment of advanced pancreatic cancer patients,the efficacy and safety of nimotuzumab is worthy of recognition.Therefore,the nimotuzumab might be one of the effective choice of patients with advanced pancreatic cancer.更多还原