本文關(guān)鍵詞： 白蛋白結(jié)合型紫杉醇 奈達(dá)鉑 宮頸癌 晚期 復(fù)發(fā) Ⅱ期臨床研究 Ⅰb和Ⅱa期宮頸癌 根治性放射治療 預(yù)后因素　出處：《北京協(xié)和醫(yī)學(xué)院》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：背景：目前,紫杉醇聯(lián)合順鉑方案為晚期、復(fù)發(fā)轉(zhuǎn)移宮頸癌化療的一線方案,臨床客觀有效率為29.1%,但應(yīng)用該方案的大部分患者仍為疾病進(jìn)展,因此臨床亟需新的有效化療方案。臨床常用紫杉醇為溶劑型紫杉醇,而白蛋白結(jié)合型紫杉醇是一種以人血白蛋白為載體的新型紫杉類化療藥,單藥應(yīng)用于復(fù)發(fā)或轉(zhuǎn)移性中晚期宮頸癌的部分緩解率為28.6%。文獻(xiàn)報(bào)道的奈達(dá)鉑在宮頸癌中的單藥有效率為46.3%。而白蛋白結(jié)合型紫杉醇聯(lián)合奈達(dá)鉑方案在宮頸癌中的臨床研究尚未見報(bào)道,因此我們進(jìn)行了這項(xiàng)單中心、前瞻性、開放性臨床研究,以評價(jià)白蛋白結(jié)合型紫杉醇聯(lián)合奈達(dá)鉑在晚期、復(fù)發(fā)轉(zhuǎn)移性宮頸癌的近期療效和安全性。 目的：評價(jià)白蛋白結(jié)合型紫杉醇聯(lián)合奈達(dá)鉑方案在晚期、復(fù)發(fā)轉(zhuǎn)移性宮頸癌的近期療效和安全性。 方法：2010年8月至2014年2月于中國醫(yī)學(xué)科學(xué)院腫瘤醫(yī)院治療的27例ⅣB期或復(fù)發(fā)轉(zhuǎn)移的宮頸癌患者,病理確診為宮頸癌,患者及家屬簽署知情同意書后給予白蛋白結(jié)合型紫衫醇175mg·m-2d1聯(lián)合奈達(dá)鉑80mg·m-2d1靜脈滴注,21天一療程,直至疾病進(jìn)展或出現(xiàn)不可耐受的不良反應(yīng)。主要研究終點(diǎn)為客觀有效率(objective response rate, ORR)及安全性,次要研究終點(diǎn)為無進(jìn)展生存時(shí)間(progress free survival, PFS)和總體生存時(shí)間(overall survival,OS)。 結(jié)果：共入組晚期、復(fù)發(fā)轉(zhuǎn)移性宮頸癌患者27例(晚期者5例,復(fù)發(fā)轉(zhuǎn)移者22例),其中26例可評價(jià)療效,27例可進(jìn)行安全性評價(jià)�；颊叩闹形荒挲g46歲；鱗癌25例(92.6%),腺癌2例(7.4%)：IVB期初治患者5例(18.5%),復(fù)發(fā)轉(zhuǎn)移患者22例(81.5%)。入組前21例(77.8%)患者接受過放療,10例(37.0%)患者接受過手術(shù),18例(66.7%)患者接受過化療,且化療方案均為含鉑方案,既往接受化療平均療程為3程(1程～9程)。 26例可評價(jià)療效患者共完成療程數(shù)92個(gè),平均療程數(shù)3.4個(gè)。完全緩解(complete response, CR)2例(7.7%),部分緩解(partial response, PR)11例(42.3%),穩(wěn)定(stable disease, SD)6例(23.1%),進(jìn)展(progression disease,PD)7例(26.9%),客觀有效率(ORR)為50.0%,死亡15例。中位PFS為9.1個(gè)月,中位OS為16.6個(gè)月。將預(yù)后相關(guān)因素的客觀有效率進(jìn)行統(tǒng)計(jì)學(xué)分析,結(jié)果顯示：晚期或復(fù)發(fā)、入組前是否放療、入組前是否化療、復(fù)發(fā)病灶是否位于放療野內(nèi)的客觀有效率差異無統(tǒng)計(jì)學(xué)意義(P均0.05),末次化療距本次治療時(shí)間大于12個(gè)月者的客觀有效率高于小于等于12個(gè)月者(71.4%vs25.0%,P=0.034)。 化療不良反應(yīng)主要是骨髓抑制、胃腸道反應(yīng)、乏力及周圍神經(jīng)感覺異常。骨髓抑制較常見,Ⅲ度中性粒細(xì)胞降低發(fā)生率為33.3%,有1例(3.7%)患者發(fā)生Ⅲ度中性粒細(xì)胞減少性發(fā)熱,Ⅲ度血小板降低和血紅蛋白降低發(fā)生率分別為7.4%和18.5%,但無1例發(fā)生Ⅳ度骨髓抑制。惡心、嘔吐發(fā)生率為81.5%,腹瀉發(fā)生率為22.2%,便秘發(fā)生率為18.5%,但均為Ⅰ-Ⅱ度不良反應(yīng)；乏力較為普遍,發(fā)生率為88.9%,Ⅲ-Ⅳ度發(fā)生率為3.7%；周圍神經(jīng)感覺異常達(dá)到51.9%,但均為Ⅰ-Ⅱ度不良反應(yīng)；沒有1例發(fā)生過敏反應(yīng)。 結(jié)論：初步研究結(jié)果提示,白蛋白結(jié)合型紫杉醇聯(lián)合奈達(dá)鉑治療晚期、復(fù)發(fā)轉(zhuǎn)移性宮頸癌的近期療效較好,毒副反應(yīng)可以耐受,遠(yuǎn)期療效還需進(jìn)一步隨訪。 目的探討Ⅰb和Ⅱa期宮頸癌根治性放射治療的療效以及影響預(yù)后的因素。 方法回顧分析1999年1月至2012年1月在中國醫(yī)學(xué)科學(xué)院腫瘤醫(yī)院行根治性放射治療的108例Ⅰb和Ⅱa期宮頸癌患者,Ⅰbl期18例(16.7%),Ⅰb2期38例(35.2%),Ⅱal期33例(30.6%),Ⅱa2期19例(17.6%)。 結(jié)果全組患者5年總生存率76.2%,5年無瘤生存率為75.6%。其中25例(23.1%)復(fù)發(fā),23例復(fù)發(fā)后死亡,2例帶瘤存活。復(fù)發(fā)者中16例(64.0%)局部復(fù)發(fā),6例(24.0%)遠(yuǎn)處轉(zhuǎn)移,3例(12.0%)局部復(fù)發(fā)+遠(yuǎn)處轉(zhuǎn)移。全組患者24例死亡,23例因腫瘤復(fù)發(fā)死亡,另1例非腫瘤原因死亡。單因素分析顯示,淋巴結(jié)轉(zhuǎn)移、療前SCC值、療后1月SCC值與Ⅰb和Ⅱa期宮頸癌的總生存時(shí)間相關(guān)。多因素分析顯示,在宮頸鱗癌中,淋巴結(jié)轉(zhuǎn)移、療后1月SCC值是影響總生存時(shí)間的主要因素。 結(jié)論Ⅰb和Ⅱa期宮頸癌根治性放療的患者中,影像學(xué)提示淋巴結(jié)轉(zhuǎn)移、療后1月SCC值末下降至1.5ng/ml的預(yù)后較差。新輔助化療后再行同步放化療對Ⅰb和Ⅱa期宮頸癌的預(yù)后可能沒有影響,根治性放療同步化療的5年總生存率有高于根治性放療的趨勢。
[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.

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.33

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本文編號：1526681