1、白蛋白结合型紫杉醇联合奈达铂在晚期、复发转移性宫颈癌中的Ⅱ期临床研究2、Ⅰb和Ⅱa期子宫颈癌患者根治性放疗的预后分析

发布时间：2018-02-23 12:55

  本文关键词： 白蛋白结合型紫杉醇 奈达铂 宫颈癌 晚期 复发 Ⅱ期临床研究 Ⅰb和Ⅱa期宫颈癌 根治性放射治疗 预后因素　出处：《北京协和医学院》2014年硕士论文　论文类型：学位论文

【摘要】：背景：目前,紫杉醇联合顺铂方案为晚期、复发转移宫颈癌化疗的一线方案,临床客观有效率为29.1%,但应用该方案的大部分患者仍为疾病进展,因此临床亟需新的有效化疗方案。临床常用紫杉醇为溶剂型紫杉醇,而白蛋白结合型紫杉醇是一种以人血白蛋白为载体的新型紫杉类化疗药,单药应用于复发或转移性中晚期宫颈癌的部分缓解率为28.6%。文献报道的奈达铂在宫颈癌中的单药有效率为46.3%。而白蛋白结合型紫杉醇联合奈达铂方案在宫颈癌中的临床研究尚未见报道,因此我们进行了这项单中心、前瞻性、开放性临床研究,以评价白蛋白结合型紫杉醇联合奈达铂在晚期、复发转移性宫颈癌的近期疗效和安全性。 目的：评价白蛋白结合型紫杉醇联合奈达铂方案在晚期、复发转移性宫颈癌的近期疗效和安全性。 方法：2010年8月至2014年2月于中国医学科学院肿瘤医院治疗的27例ⅣB期或复发转移的宫颈癌患者,病理确诊为宫颈癌,患者及家属签署知情同意书后给予白蛋白结合型紫衫醇175mg·m-2d1联合奈达铂80mg·m-2d1静脉滴注,21天一疗程,直至疾病进展或出现不可耐受的不良反应。主要研究终点为客观有效率(objective response rate, ORR)及安全性,次要研究终点为无进展生存时间(progress free survival, PFS)和总体生存时间(overall survival,OS)。 结果：共入组晚期、复发转移性宫颈癌患者27例(晚期者5例,复发转移者22例),其中26例可评价疗效,27例可进行安全性评价。患者的中位年龄46岁；鳞癌25例(92.6%),腺癌2例(7.4%)：IVB期初治患者5例(18.5%),复发转移患者22例(81.5%)。入组前21例(77.8%)患者接受过放疗,10例(37.0%)患者接受过手术,18例(66.7%)患者接受过化疗,且化疗方案均为含铂方案,既往接受化疗平均疗程为3程(1程～9程)。 26例可评价疗效患者共完成疗程数92个,平均疗程数3.4个。完全缓解(complete response, CR)2例(7.7%),部分缓解(partial response, PR)11例(42.3%),稳定(stable disease, SD)6例(23.1%),进展(progression disease,PD)7例(26.9%),客观有效率(ORR)为50.0%,死亡15例。中位PFS为9.1个月,中位OS为16.6个月。将预后相关因素的客观有效率进行统计学分析,结果显示：晚期或复发、入组前是否放疗、入组前是否化疗、复发病灶是否位于放疗野内的客观有效率差异无统计学意义(P均0.05),末次化疗距本次治疗时间大于12个月者的客观有效率高于小于等于12个月者(71.4%vs25.0%,P=0.034)。 化疗不良反应主要是骨髓抑制、胃肠道反应、乏力及周围神经感觉异常。骨髓抑制较常见,Ⅲ度中性粒细胞降低发生率为33.3%,有1例(3.7%)患者发生Ⅲ度中性粒细胞减少性发热,Ⅲ度血小板降低和血红蛋白降低发生率分别为7.4%和18.5%,但无1例发生Ⅳ度骨髓抑制。恶心、呕吐发生率为81.5%,腹泻发生率为22.2%,便秘发生率为18.5%,但均为Ⅰ-Ⅱ度不良反应；乏力较为普遍,发生率为88.9%,Ⅲ-Ⅳ度发生率为3.7%；周围神经感觉异常达到51.9%,但均为Ⅰ-Ⅱ度不良反应；没有1例发生过敏反应。 结论：初步研究结果提示,白蛋白结合型紫杉醇联合奈达铂治疗晚期、复发转移性宫颈癌的近期疗效较好,毒副反应可以耐受,远期疗效还需进一步随访。 目的探讨Ⅰb和Ⅱa期宫颈癌根治性放射治疗的疗效以及影响预后的因素。 方法回顾分析1999年1月至2012年1月在中国医学科学院肿瘤医院行根治性放射治疗的108例Ⅰb和Ⅱa期宫颈癌患者,Ⅰbl期18例(16.7%),Ⅰb2期38例(35.2%),Ⅱal期33例(30.6%),Ⅱa2期19例(17.6%)。 结果全组患者5年总生存率76.2%,5年无瘤生存率为75.6%。其中25例(23.1%)复发,23例复发后死亡,2例带瘤存活。复发者中16例(64.0%)局部复发,6例(24.0%)远处转移,3例(12.0%)局部复发+远处转移。全组患者24例死亡,23例因肿瘤复发死亡,另1例非肿瘤原因死亡。单因素分析显示,淋巴结转移、疗前SCC值、疗后1月SCC值与Ⅰb和Ⅱa期宫颈癌的总生存时间相关。多因素分析显示,在宫颈鳞癌中,淋巴结转移、疗后1月SCC值是影响总生存时间的主要因素。 结论Ⅰb和Ⅱa期宫颈癌根治性放疗的患者中,影像学提示淋巴结转移、疗后1月SCC值末下降至1.5ng/ml的预后较差。新辅助化疗后再行同步放化疗对Ⅰb和Ⅱa期宫颈癌的预后可能没有影响,根治性放疗同步化疗的5年总生存率有高于根治性放疗的趋势。
[Abstract]:Background: at present, paclitaxel combined with cisplatin as the first-line chemotherapy of advanced, recurrence and metastasis of cervical cancer, the clinical response rate was 29.1%, but most of the schemes were still used for disease progression, so the clinical urgently needed new chemotherapy. The clinical commonly used paclitaxel as solvent based paclitaxel and albumin bound paclitaxel. Alcohol is a kind of Human Albumin as the carrier of the new taxane chemotherapy drug, single drug used in recurrent or metastatic cervical carcinoma of the partial remission rate was nedaplatin 28.6%. reported in cervical cancer rate for the clinical research of 46.3%. and albumin bound paclitaxel combined with nedaplatin in cervical cancer in has not been reported, so we conducted a single center, prospective, open clinical study, the type of paclitaxel combined with Nedaplatin Combined with the evaluation of albumin in the late recurrence and transfer Recent efficacy and safety of cervical cancer.
Objective: To evaluate the short-term efficacy and safety of albumin binding paclitaxel combined with nedaplatin in the late stage of recurrent metastatic cervical cancer.
Methods: from August 2010 to February 2014 in the Cancer Hospital of Chinese Academy of medical treatment of 27 cases of B stage IV recurrence or metastasis of cervical cancer patients, diagnosed as cervical cancer patients and their families signed the informed consent given albumin bound paclitaxel 175mg - m-2d1 80mg - m-2d1 combined with nedaplatin intravenous injection, 21 days a course of treatment, until disease progression or adverse reactions can not be tolerated. The primary end point was the objective response rate (objective response, rate, ORR) and the safety of the secondary end point was progression free survival time (Progress free, survival, PFS) and overall survival (overall, survival, OS).
Results: a total of 27 cases of late stage group, cervical cancer patients with metastasis and recurrence (5 cases, 22 cases of late recurrence and metastasis), of which 26 evaluable cases, 27 cases to evaluate the safety of the patients. The median age was 46 years; 25 cases of squamous cell carcinoma (92.6%), 2 cases of adenocarcinoma (7.4%:IVB) period 5 cases of newly diagnosed patients (18.5%), recurrence and metastasis in 22 patients (81.5%). Before entering the group of 21 cases (77.8%) patients received radiotherapy, 10 cases (37%) underwent surgery, 18 cases (66.7%) patients received chemotherapy and chemotherapy for platinum based regimens, past the average duration of chemotherapy 3 (1 ~ 9 Cheng Cheng).
26 evaluable patients completed a total of 92 courses of treatment, the average number of 3.4. The complete remission (complete response, CR) in 2 cases (7.7%), partial remission (partial, response, PR) in 11 cases (42.3%), stable (stable disease, SD) in 6 cases (23.1%), progress (progression disease PD), 7 cases (26.9%), the objective response rate (ORR) was 50%, 15 cases died. The median PFS was 9.1 months, median OS was 16.6 months. The effective rate of objective prognostic factors were statistically analyzed, results showed: advanced or recurrent, into the group before radiotherapy, into the group before chemotherapy, there was no significant difference in effective rate of recurrent lesions is objective in the field of radiotherapy (P 0.05), the objective response rate from the last chemotherapy treatment for more than 12 months is higher than that of less than or equal to 12 months (71.4%vs25.0%, P=0.034).
The adverse reaction of chemotherapy was mainly bone marrow suppression, gastrointestinal reactions, fatigue and peripheral nerve paresthesia. Myelosuppression is common, grade III neutropenia incidence was 33.3%, 1 cases (3.7%) occurred in patients with grade III neutropenia and fever, thrombocytopenia and lower hemoglobin of incidence was 7.4% 18.5% and 1 cases, but no degree of myelosuppression. Nausea, vomiting, the incidence rate was 81.5%, the incidence of diarrhea was 22.2%, the incidence of constipation was 18.5%, but was I-II degree of adverse reactions; fatigue is more common, the incidence rate was 88.9%, III - IV degree of incidence was 3.7%; peripheral nerve the abnormal reached 51.9%, but for the I-II degree of adverse reactions occurred in 1 cases; no allergic reaction.
Conclusion: the preliminary results suggest that albumin bound paclitaxel combined with nedaplatin is effective in the treatment of advanced cervical cancer.
Objective to investigate the effect of radical radiation therapy on cervical cancer in stage I B and II A and the factors that affect the prognosis.
Methods from January 1999 to January 2012, 108 patients with stage I B and II a cervical cancer who received radical radiotherapy at the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. There were 18 cases (16.7%) in stage BL, 16.7% cases in stage BL, 38 cases (35.2%) in stage I, 33 cases (30.6%) in stage II Al, 19 cases (17.6%) in stage II A2.
Results all patients 5 year survival rate was 76.2%, 5 years survival rate was 25 (23.1%) 75.6%. cases including 23 cases of recurrence and death after recurrence, 2 cases with tumor recurrence survival. In 16 cases (64%) of local recurrence, distant metastasis in 6 cases (24%), 3 cases (12%) local recurrence and distant metastasis. All patients 24 cases died, 23 cases died of tumor recurrence, another 1 cases of non tumor death. Univariate analysis showed that lymph node metastasis, before treatment after treatment SCC value, SCC value and B January I and II stage a cervical cancer survival. Multivariate analysis show that in cervical squamous cell carcinoma, lymph node metastasis, January after treatment SCC value is the main factor affecting overall survival.
Conclusion radical radiotherapy of B and cervical carcinoma in stage a patients, radiographic evidence of lymph node metastasis, the prognosis is poor at the end of January SCC value dropped to 1.5ng/ml after the treatment. After neoadjuvant chemotherapy and radiotherapy and chemotherapy on the prognosis of B and cervical carcinoma in stage a may have no effect, radical radiotherapy with the 5 year overall survival rate is higher than the radical radiotherapy trend.

【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.33

【参考文献】

中国期刊全文数据库 前3条

1 江泽飞,宋三泰,冯奉仪,黄惠芳,邓小虹,鲍云华,张湘茹,刘丽影,沈铿,黄荣丽,朗景和,段微;国产紫杉醇注射液治疗100例恶性肿瘤[J];中国肿瘤临床与康复;2000年02期

2 程玺,蔡树模,李子庭,薛木泉,吴小华,臧荣余;淋巴结转移的Ⅰb1~Ⅱb期子宫颈癌患者手术后的综合治疗及预后分析[J];中华妇产科杂志;2005年08期

3 应倩;夏庆民;郑荣寿;张思维;陈万青;;中国2009年宫颈癌发病与死亡分析[J];中国肿瘤;2013年08期

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