王庭豐，呂進(jìn) ，周國志

(1滁州市第一人民醫(yī)院，安徽滁州244000; 2南京醫(yī)科大學(xué)附屬南京醫(yī)院；3南京醫(yī)科大學(xué)附屬明德醫(yī)院)

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卡鉑、紫杉醇新輔助化療對食管癌患者心臟功能的影響

王庭豐1，呂進(jìn)2，周國志3

(1滁州市第一人民醫(yī)院，安徽滁州244000; 2南京醫(yī)科大學(xué)附屬南京醫(yī)院；3南京醫(yī)科大學(xué)附屬明德醫(yī)院)

摘要：目的觀察卡鉑、紫杉醇聯(lián)合新輔助化療對食管癌患者心臟功能的影響。方法 46例食管癌患者術(shù)前行卡鉑聯(lián)合紫杉醇新輔助化療5周。 每例患者化療前后計數(shù)心率，測量收縮壓及舒張壓，檢測血清肌酸激酶、肌酸激酶同工酶、腦鈉肽和肌鈣蛋白，心臟彩超檢查測左心室收縮末容積、左心室舒張末容積、左心室射血分?jǐn)?shù)、左心室容量、下腔靜脈血流速度。對化療后各指標(biāo)變化行單因素Logistic回歸分析，并計算變化值和95%可信區(qū)間(95%CI)。結(jié)果46例食管癌患者接受卡鉑聯(lián)合紫杉醇聯(lián)合新輔助化療5周后收縮壓平均下降18 mmHg，95%CI為(-25,-10),P<0.05；舒張壓平均下降6 mmHg，95%CI為(-14，-2),P<0.05；心率平均增加5次/min，95%CI為(1，11) ,P<0.05；肌鈣蛋白平均升高0.008 mmol/L,95%CI為(-0.002，-0.012),P<0.05；肌酸激酶平均升高42 IU/L，95%CI為(18，71),P<0.05；左心室容量平均下降54 mL，95%CI為(-72，-39),P<0.05。結(jié)論 接受卡鉑、紫杉醇聯(lián)合新輔助化療的食管癌患者，血清心肌肌酸激酶上升，收縮壓及舒張壓降低，心室容量變小。

關(guān)鍵詞：食管癌；卡鉑；紫杉醇；新輔助化療；心臟功能

食管癌發(fā)病率位居惡性腫瘤的第8位[1]。其發(fā)現(xiàn)時多為中晚期，只有50%左右有機(jī)會接受手術(shù)治療[2]。新輔助化療能有效減小腫瘤體積，降低腫瘤分期，給不能手術(shù)的食管癌患者帶來了手術(shù)機(jī)會，但也可能對患者的臟器功能產(chǎn)生負(fù)面影響[3，4]。2013年1月1日～2015年6月31日，我們對46例食管癌患者術(shù)前采用卡鉑、紫杉醇聯(lián)合化療方案行新輔助化療5周，觀察治療前后患者心臟功能的變化?，F(xiàn)報告如下。

1資料與方法

1.1臨床資料本組患者男38例，女8例；年齡45～72歲、平均63.7歲；體質(zhì)量50～112 kg、平均70 kg；身高153～178 cm、平均165 cm；吸煙13例，合并高血壓12例。腫瘤直徑3.4～15 cm、平均7.6 cm；腺癌37例，鱗癌9例；臨床分期ⅠB期6例，ⅡA期 6例，ⅡB期2例，ⅢA期10例，ⅢB期10例，未分期12例。排除標(biāo)準(zhǔn)：①接受其他藥物化療者；②化療期間或者以前接受過放療者；③化療前已有心臟系統(tǒng)疾病者；④伴有其他系統(tǒng)疾病者。

1.2新輔助化療方法卡鉑、紫杉醇各50 mg/m2靜滴，每周1次，治療5周。

1.3心臟功能觀察方法每例患者化療前后計數(shù)心率，用校準(zhǔn)后的臺式血壓計測量收縮壓及舒張壓，抽取空腹靜脈測血清肌酸激酶、肌酸激酶同工酶、腦鈉肽和肌鈣蛋白，行心臟彩超檢查測左心室收縮末容積、左心室舒張末容積、左心室射血分?jǐn)?shù)、左心室容量、下腔靜脈血流速度。

1.4統(tǒng)計學(xué)方法采用STATA11.0統(tǒng)計軟件。對化療后各指標(biāo)變化行單因素Logistic回歸分析，并計算變化值和95%可信區(qū)間(95%CI)。P<0.05為差異有統(tǒng)計學(xué)意義。

2結(jié)果

46例食管癌患者接受卡鉑聯(lián)合紫杉醇新輔助化療5周后收縮壓平均下降18 mmHg，95%CI為(-25,-10),P<0.05；舒張壓平均下降6 mmHg，95%CI為(-14，-2),P<0.05；心率平均增加5次/min，95%CI為(1，11) ,P<0.05；血清肌鈣蛋白平均升高0.008 mmol/L,95%CI為(-0.002，-0.012),P<0.05；血清肌酸激酶平均升高42 IU/L，95%CI為(18，71),P<0.05；左心室容量平均下降54 mL，95%CI為(-72，-39)，P<0.05。血清肌酸激酶同工酶平均升高0.2 mmol/L, 95%CI為(0.1，0.7)，P=0.16；血清腦鈉肽平均升高4 mmol/L,95%CI為(-15,22)，P=0.07；左心室收縮末容積平均下降3 mL,95%CI為(-8,5),P=0.613；左心室舒張末容積平均下降8 mL,95%CI為(-16,4)，P=0.172；下腔靜脈血流速度平均增加6 m/s,95%CI為(2,-12),P=0.072。

3討論

食管癌手術(shù)較大，術(shù)前需要綜合評估患者的耐受程度。本研究結(jié)果顯示，接受卡鉑聯(lián)合紫杉醇新輔助化療的患者，收縮壓及舒張壓降低，心率升高，說明新輔助化療患者血容量有所降低，并出現(xiàn)心率加快以代償心室容量降低。如果血壓持續(xù)降低,必將影響冠狀動脈的血流，從而影響心肌舒張期的供血，短期可引起心肌損害并出現(xiàn)心肌酶譜的改變，長時間心肌損害則可以引起心臟的代償性改變，導(dǎo)致心衰甚至心源性猝死[6]。

本研究結(jié)果顯示，5周新輔助化療后患者收縮壓降低的95%CI為10～25 mmHg。有報道稱，新輔助化療藥物對服用高血壓藥物的患者收縮壓影響更大，特別是使用α受體阻斷劑的患者，其收縮壓下降更顯著[7]。5-FU聯(lián)合順鉑治療食管癌有可能會導(dǎo)致心律失常、心絞痛、心肌梗死、心衰，甚至猝死[8]。此方案的心臟毒性最大可能是來自鉑類藥物，一項鉑類聯(lián)合其他藥物治療睪丸癌轉(zhuǎn)移的研究中也發(fā)現(xiàn)其存在心肌損害[9，10]。紫杉醇的心肌損害主要為心動過緩，其導(dǎo)致心衰的風(fēng)險也不容忽視[11,12]。本研究結(jié)果顯示，患者化療5周后血清肌鈣蛋白平均升高0.008 mmol/L,肌酸激酶升高42 U/L，說明接受新輔助化療的患者血清心肌酶譜明顯發(fā)生了改變，心臟受損。左心室負(fù)責(zé)為全身器官供血，左心室射血分?jǐn)?shù)如果低于50%表示左心室功能明顯受到了損害?；颊唠m不出現(xiàn)臨床癥狀，但其儲備功能已經(jīng)不足，不能耐受手術(shù)治療[13~15]。本組患者接受卡鉑、紫杉醇聯(lián)合新輔助化療5周后,心臟射血分?jǐn)?shù)有所降低，雖然沒有統(tǒng)計學(xué)意義，不過我們化療的療程短，隨訪時間也短，尚不能說明新輔助化療對食管癌患者的心室功能沒有影響。

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Effects of carboplatin combined with paclitaxel in neoadjuvant chemotherapy on cardiac function of patients with esophageal cancer

WANGTingfeng1,LYUJin,ZHOUGuozhi

(1TheFirstPeople'sHospitalofChuzhou,Chuzhou244000,China)

Abstract:ObjectiveTo evaluate the effects of carboplatin combined with paclitaxel during neoadjuvant chemotherapy on cardiac function of patients with esophageal cancer.MethodsTotally 46 patients with esophageal cancer received the neoadjuvant chemotherapy with carboplatin and paclitaxel for 5 weeks before the operation. We recorded the heart rate, measured the systolic blood pressure and diastolic blood pressure, detected the blood creatine kinase, creatine kinase isoenzyme, brain natriuretic peptide and troponin, and examined the left ventricular end-systolic volume, left ventricular end-diastolic volume, left ventricular ejection fraction, ventricular volume and blood flow velocity of inferior vena cava before and after chemotherapy. Univariate Logistic regression analysis was conducted on the index changes after chemotherapy, and the change value and 95% confidence interval (95%CI) were calculated.ResultsAfter 46 patients with esophageal cancer received the neoadjuvant chemotherapy with carboplatin and paclitaxel for 5 weeks, the systolic blood pressure dropped an average of 18 mmHg, 95%CI (25, -10), P<0.05; diastolic blood pressure dropped an average of 6 mmHg, 95%CI (-14, -2), P<0.05; the heart rate increased an average of 5/min, 95%CI(1, 11), P<0.05; troponin increased an average of 0.008 mmol/L, 95%CI(-0.002, -0.012), P<0.05; creatine kinase increased an average of 42 IU/L, 95%CI(18, 71), P<0.05; and ventricular volume dropped an average of 54 mL, 95%CI(-72, -39), P<0.05. No significant differences were found in the rest of indexes before and after surgery.ConclusionThe myocardial creatine kinase increased, systolic blood pressure and diastolic blood pressure decreased and the ventricular size became smaller in patients with esophageal cancer receiving neoadjuvant chemotherapy of carboplatin and paclitaxel.

Key words:esophageal carcinoma; carboplatin; paclitaxel; neoadjuvant chemotherapy; heart function

(收稿日期：2015-10-22)

中圖分類號：R735.1

文獻(xiàn)標(biāo)志碼：A

文章編號：1002-266X(2016)06-0007-03

doi：10.3969/j.issn.1002-266X.2016.06.002

作者簡介：第一王庭豐(1985-),男,本科,醫(yī)師,主要研究方向為腫瘤化療基礎(chǔ)與臨床。E-mail: wantingfeng1233@qq.com

基金項目：國家自然科學(xué)基金青年基金資助項目(81201881)。