畢金玲 劉海源 黃勇
阿帕替尼單藥治療進(jìn)展期非小細(xì)胞肺癌療效觀察
畢金玲 劉海源 黃勇
目的 探索阿帕替尼單藥治療進(jìn)展期非小細(xì)胞肺癌(NSCLC)的療效和安全性。方法 選取進(jìn)展期NSCLC患者共65例。隨機(jī)分為對(duì)照組(n=30),行多西他賽化療;治療組(n=35),行阿帕替尼治療。對(duì)兩組患者進(jìn)行療效和毒副反應(yīng)評(píng)價(jià)。結(jié)果 對(duì)照組完全緩解0例,部分緩解3例,穩(wěn)定11例,進(jìn)展16例,治療組完全緩解0例,部分緩解6例,穩(wěn)定17例,進(jìn)展12例,P<0.05。阿帕替尼毒副反應(yīng)可控,較對(duì)照組毒副反應(yīng)發(fā)生率顯著降低。結(jié)論 阿帕替尼對(duì)進(jìn)展期NSCLC具有一定療效和可耐受的毒性。
阿帕替尼;非小細(xì)胞肺癌;多西他賽;進(jìn)展期
肺癌為常見(jiàn)惡性腫瘤,據(jù)統(tǒng)計(jì),2015年美國(guó)新增肺癌病例221200例,死亡158040例,占腫瘤死亡病例27%[1]。肺癌可分為非小細(xì)胞肺癌(NSCLC)和小細(xì)胞肺癌(SCLC)兩大類(lèi),其中非小細(xì)胞肺癌又分為腺癌和鱗癌兩種亞型。臨床實(shí)踐中,非小細(xì)胞肺癌的標(biāo)準(zhǔn)一線治療方案為鉑類(lèi)藥物聯(lián)用方案[2]。美國(guó)批準(zhǔn)用于治療進(jìn)展期NSCLC二線治療的靶向藥物主要為雷莫蘆單抗和厄洛替尼[3-6]。靶向治療藥物的出現(xiàn),如單克隆抗體,小分子激酶抑制劑等使得抗腫瘤治療方式更加個(gè)體化、特異化[7]。新近開(kāi)放的治療藥物定位于腫瘤的免疫學(xué)機(jī)制[8]。阿帕替尼作為分子靶向藥物目前已經(jīng)廣泛應(yīng)用于消化道惡性腫瘤,尤其在胃癌和肝癌的多線治療中。但是,阿帕替尼對(duì)于其它惡性腫瘤的治療療效和安全性觀察尚不完全明確。本研究通過(guò)對(duì)非小細(xì)胞肺癌患者中應(yīng)用阿帕替尼單藥治療的療效評(píng)估,初步了解其對(duì)于其它腫瘤的作用效應(yīng)。
一、研究對(duì)象
選取2014年1月-2016年3月間,我院收治的65例診斷為復(fù)發(fā)性非小細(xì)胞肺癌患者作為研究對(duì)象?;颊呷脒x標(biāo)準(zhǔn)為:① 年齡18歲-70歲之間,男女不限;② 經(jīng)病理組織學(xué)和/或細(xì)胞學(xué)明確診斷為NSCLC;③ EGFR野生型的非小細(xì)胞肺癌患者;④ 具有可測(cè)量病灶(螺旋CT掃描大于10mm,滿(mǎn)足RECIST1.1標(biāo)準(zhǔn));⑤ 二線治療失敗的晚期非小細(xì)胞肺癌患者(注:a.治療失敗的定義:治療過(guò)程中疾病進(jìn)展或治療結(jié)束后腫瘤復(fù)發(fā)轉(zhuǎn)移,或出現(xiàn)不可耐受的毒性;b.進(jìn)展期疾病每一線的治療包括用藥時(shí)間≥1個(gè)周期或者更長(zhǎng)時(shí)間的一種或者多種化療藥物);⑥ 患者經(jīng)評(píng)估KPS評(píng)分70分以上;⑦ 預(yù)計(jì)生存期≥3個(gè)月。排除標(biāo)準(zhǔn):① 終末期患者無(wú)法耐受治療;② 既往合并慢性基礎(chǔ)性疾病經(jīng)評(píng)估可能對(duì)于治療產(chǎn)生干擾;③ 合并嚴(yán)重肝腎功能損害。評(píng)估標(biāo)準(zhǔn):根據(jù)1.1版RECST標(biāo)準(zhǔn),完全緩解(CR),部分緩解(PR),穩(wěn)定(SD)和進(jìn)展(PD),PR+CR為客觀緩解效率(0RR),PR+CR+SD為疾病控制率(DCR)。
二、研究方法
65例患者隨機(jī)分為對(duì)照組和治療組,對(duì)照組30例患者接受多西他賽75mg/m2d1化療,21天為一周期。兩個(gè)用藥周期為一個(gè)觀察周期,兩個(gè)觀察周期為一個(gè)療效評(píng)價(jià)周期。治療組35例患者接受阿帕替尼治療,劑量500mg/d,連用28天為一個(gè)給藥和觀察周期,兩個(gè)觀察周期為一個(gè)療效評(píng)價(jià)周期。患者每周行血常規(guī)及生化指標(biāo)的全面檢測(cè),評(píng)估藥物不良反應(yīng)(AE)。當(dāng)出現(xiàn)病情進(jìn)展,嚴(yán)重毒性反應(yīng)影響遠(yuǎn)期治療以及患者主動(dòng)退出研究時(shí),治療予以終止。
三、統(tǒng)計(jì)學(xué)方法
應(yīng)用SPSS 19.0軟件進(jìn)行數(shù)據(jù)分析,兩組間比較采用χ2檢驗(yàn),P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
一、患者療效評(píng)估結(jié)果
治療組中,客觀緩解率ORR(17.14%)和疾病控制率DCR(65.71%)均顯著高于對(duì)照組,P<0.05,(見(jiàn)表1)。
表1 患者療效評(píng)估結(jié)果
二、毒性反應(yīng)評(píng)估結(jié)果
65例患者均未出現(xiàn)治療相關(guān)性死亡。對(duì)照組中血液系毒性、乏力、食欲下降及高膽紅素血癥反應(yīng)均顯著升高。治療組毒副反應(yīng)發(fā)生率均較低,且未發(fā)生Ⅳ度嚴(yán)重不良反應(yīng),所有不良事件都是可耐受和可控制的,P<0.05。(見(jiàn)表2)。
近年來(lái),對(duì)于腫瘤控制的研究方向主要集中在內(nèi)皮生長(zhǎng)因子(VEGF)通路的阻斷。靶向治療機(jī)制在于降低激活的和游離狀態(tài)的VEGF濃度并切斷VEGF與其受體(VEGFR)信號(hào)的傳導(dǎo)通路。進(jìn)展期NSCLC的標(biāo)準(zhǔn)化療方案為以鉑類(lèi)藥物為基礎(chǔ)的二聯(lián)療法。多項(xiàng)研究指出,在既定的鉑類(lèi)方案中增加化療藥物對(duì)于NSCLC患者的預(yù)后并無(wú)顯著改善,且可能導(dǎo)致藥物毒性增加[9]??寡苌傻陌邢蛩幬飳?duì)于進(jìn)展期NSCLC的治療發(fā)揮至關(guān)重要的作用,重組人單克隆抗體貝伐單抗與VEGF競(jìng)爭(zhēng)性結(jié)合進(jìn)而抑制腫瘤血管生成,是目前唯一批準(zhǔn)用于NSCLC治療的抗血管生成藥物[10]。
阿帕替尼是中國(guó)自主研發(fā)的第一代口服靶向藥,其主要靶位點(diǎn)為VEGFR-2和酪氨酸激酶受體(RTK)[11]。在多項(xiàng)腫瘤藥物的研究中,阿帕替尼通過(guò)阻斷VEGFR-2從而抑制內(nèi)皮增殖并最終抑制血管生成[12]。從本研究療效評(píng)估中可見(jiàn),相比較于傳統(tǒng)三線化療方案,阿帕替尼療效更為確定。在毒副反應(yīng)的對(duì)比中發(fā)現(xiàn),對(duì)照組血液毒性反應(yīng)顯著高于治療組,這也提示阿帕替尼在用藥的安全性方面值得肯定。我們的研究結(jié)果與Hu[13]和Qin[14]的報(bào)告相一致。阿帕替尼常見(jiàn)毒副反應(yīng)為高血壓和手足綜合征。在本研究中,阿帕替尼設(shè)定劑量為500g/天,毒性反應(yīng)呈現(xiàn)出可控性和耐受性。有研究指出,阿帕替尼劑量水平為750mg/天時(shí)安全性和耐受性仍然可以保障[15]。
表2 藥物毒性反應(yīng)評(píng)估結(jié)果
綜上所述,本研究通過(guò)對(duì)NSCLC患者中應(yīng)用阿帕替尼單藥治療的療效進(jìn)行評(píng)估,初步明確了阿帕替尼在NSCLC三線治療中的療效及其毒副作用。分子靶向藥物阿帕替尼能夠有效抑制腫瘤血管生成,在NSCLC的治療中具有一定療效和可耐受的毒性。
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Effect of apatinib as single agent on advanced non-small cell lung cancer
BI Jin-ling, LIU Hai-yuan, HUANG Yong
Oncology Department, the 2nd People’s Hospital of Hefei, Hefei, Anhui 230000, China
Objective To evaluate the efficacy and safety of apatinib as single-agent in treatment of advanced non-small cell lung cancer (NSCLC). Methods A total of 65 patients with relapse NSCLC were enrolled and divided into two groups. The control group (n=30) was given docetaxel and the treatment group (n=30) was given apatinib. All patients were evaluated for efficacy and safety. Results There was no case of complete response, 3 cases of partial response, 11 stable cases and 16 advanced case in the control group, and no case of complete response, 6 cases of partial response, 17 stable cases and 12 advanced cases in the treatment group (P<0.05). Compared with the control group, the toxicity of single agent was controllable with significant lower incidence of Ⅲ-VI adverse reaction. Conclusion Apatinib has certain curative efficacy and tolerable toxicity in treatment of advanced NSCLC.
apatinib; non-small cell lung cancer; docetaxel; advanced
10.3969/j.issn.1009-6663.2017.08.034
230000 安徽 合肥,合肥市第二人民醫(yī)院腫瘤科
黃勇,E-mail:hy670716@163.com
2016-12-16]