顺铂加或不加尼妥珠单抗同步放化疗治疗局部晚期宫颈癌

发布时间：2018-03-06 05:14

本文选题：表皮生长因子受体　切入点：宫颈癌　出处：《浙江大学》2015年硕士论文　论文类型：学位论文

【摘要】：宫颈癌是女性第二大常见恶性肿瘤,也是女性主要的死亡原因。含铂方案的同步放化疗是局部晚期宫颈癌的标准治疗,但治疗后大多数患者为部分缓解或缓解时间较短,超过35%的患者肿瘤持续存在、复发或转移,需要寻找一些新的药物或方法来提高疗效。研究发现,宫颈癌中存在表皮生长因子受体(EGFR)过度表达,与肿瘤对细胞毒药物及放疗抵抗有关。体内、外研究均发现,阻断EGFR可增加肿瘤的放疗敏感性。尼妥珠单抗是一种纯人源化的EGFR单克隆抗体,可以明显降低EGFR的磷酸化,在头颈部、结直肠癌等肿瘤中已经显示了较好的抗肿瘤活性。因此联合顺铂同步放化疗治疗局部晚期宫颈癌可能可以增加疗效。目的：本研究旨在比较观察顺铂加或不加尼妥珠单抗同步放化疗治疗局部晚期宫颈癌的疗效及毒副作用。方法：20例局部晚期宫颈癌患者随机接受顺铂同步放化疗(对照组)或者尼妥珠单抗联合顺铂同步放化疗(观察组),每两周采用MRI测量肿瘤体积,主要观察终点为肿瘤退缩速度,次要观察终点为毒副反应评价及生存率(OS)和无进展生存率(PFS)。采用免疫组化法检测宫颈癌EGFR表达、RT-PCR检测EGFR突变情况。结果：尼妥珠单抗联合顺铂同步放化疗在治疗2周时肿瘤退缩明显更快(P0.049),而4周(P=0.063)、6周(P=0.15)、8周(P=0.234)时无明显差异；血液学和非血液学毒性两组相似。4年PFS观察组为58.3%,对照组为33.3%(P=0.246),4年OS观察组80%,对照组为70%(P=0.584)。EGFR表达率为25%,EGFR突变率为30%。结论：尼妥珠单抗联合顺铂同步放化疗治疗局部晚期宫颈癌可以加快肿瘤早期退缩速度,提高疗效,安全性好。本研究EGFR表达率为25%,EGFR存在18-21外显子突变,但两者与尼妥珠单抗疗效是否相关尚不清楚,需要进一步观察。
[Abstract]:Cervical cancer is the second most common malignant tumor in women and the leading cause of death in women. Chemotherapy and radiotherapy with platinum regimen is the standard treatment for locally advanced cervical cancer. More than 35% patients have tumors that persist, recur or metastasize, and new drugs or methods need to be found to improve their efficacy. Studies have found that epidermal growth factor receptor (EGFR) overexpression is present in cervical cancer. In vivo and in vitro, blocking EGFR can increase the radiosensitivity of tumor. Nitozumab is a pure human monoclonal antibody to EGFR, which can significantly reduce the phosphorylation of EGFR. In the head and neck, colorectal cancer and other tumors have shown good anti-tumor activity, so the combination of cisplatin combined with radiotherapy and chemotherapy may be able to increase the efficacy of locally advanced cervical cancer. Objective: to compare the efficacy and side effects of cisplatin plus or no niytozumab in the treatment of locally advanced cervical cancer. Methods Twenty patients with locally advanced cervical cancer were randomly given cisplatin concurrent radiotherapy and chemotherapy (control group) or Nietozumab combined with cisplatin concurrent chemotherapy (observation group). Tumor volume was measured by MRI every two weeks. The main endpoints were tumor withdrawal rate, and the end points were toxicity evaluation and survival rate (OS) and progressive survival rate (PFS). Immunohistochemical method was used to detect EGFR expression in cervical cancer and RT-PCR was used to detect EGFR mutation. Results: Nietozumab combined with cisplatin concurrent radiotherapy and chemotherapy had no significant difference at 2 weeks after treatment with P0. 049, but 4 weeks with P0. 063 and 6 weeks with P0. 15 and P0. 234. The toxicity of hematology and non-hematology was similar between the two groups: 58.3in the PFS observation group in 4 years, 0.246 in the control group, 80in the OS observation group for 4 years, and in the control group, the expression rate of 0.584o.EGFR in the control group was 250.584. the mutation rate of EGFR was 30. Conclusion: Niytozumab combined with cisplatin concurrent radiotherapy and chemotherapy can accelerate the early withdrawal rate of local advanced cervical cancer, improve the efficacy and safety. The expression rate of EGFR in this study is 25% EGFR exon 18-21 mutation. However, it is not clear whether the two are related to the efficacy of Nitozumab, and need further observation.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R734.2

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