卡铂、紫杉醇新辅助化疗对食管癌患者心脏功能的影响

王庭丰，吕进 ，周国志

(1滁州市第一人民医院，安徽滁州244000; 2南京医科大学附属南京医院；3南京医科大学附属明德医院)



卡铂、紫杉醇新辅助化疗对食管癌患者心脏功能的影响

王庭丰1，吕进2，周国志3

(1滁州市第一人民医院，安徽滁州244000; 2南京医科大学附属南京医院；3南京医科大学附属明德医院)

摘要：目的观察卡铂、紫杉醇联合新辅助化疗对食管癌患者心脏功能的影响。方法 46例食管癌患者术前行卡铂联合紫杉醇新辅助化疗5周。 每例患者化疗前后计数心率，测量收缩压及舒张压，检测血清肌酸激酶、肌酸激酶同工酶、脑钠肽和肌钙蛋白，心脏彩超检查测左心室收缩末容积、左心室舒张末容积、左心室射血分数、左心室容量、下腔静脉血流速度。对化疗后各指标变化行单因素Logistic回归分析，并计算变化值和95%可信区间(95%CI)。结果46例食管癌患者接受卡铂联合紫杉醇联合新辅助化疗5周后收缩压平均下降18 mmHg，95%CI为(-25,-10),P<0.05；舒张压平均下降6 mmHg，95%CI为(-14，-2),P<0.05；心率平均增加5次/min，95%CI为(1，11) ,P<0.05；肌钙蛋白平均升高0.008 mmol/L,95%CI为(-0.002，-0.012),P<0.05；肌酸激酶平均升高42 IU/L，95%CI为(18，71),P<0.05；左心室容量平均下降54 mL，95%CI为(-72，-39),P<0.05。结论 接受卡铂、紫杉醇联合新辅助化疗的食管癌患者，血清心肌肌酸激酶上升，收缩压及舒张压降低，心室容量变小。

关键词：食管癌；卡铂；紫杉醇；新辅助化疗；心脏功能

食管癌发病率位居恶性肿瘤的第8位[1]。其发现时多为中晚期，只有50%左右有机会接受手术治疗[2]。新辅助化疗能有效减小肿瘤体积，降低肿瘤分期，给不能手术的食管癌患者带来了手术机会，但也可能对患者的脏器功能产生负面影响[3，4]。2013年1月1日～2015年6月31日，我们对46例食管癌患者术前采用卡铂、紫杉醇联合化疗方案行新辅助化疗5周，观察治疗前后患者心脏功能的变化。现报告如下。

1资料与方法

1.1临床资料本组患者男38例，女8例；年龄45～72岁、平均63.7岁；体质量50～112 kg、平均70 kg；身高153～178 cm、平均165 cm；吸烟13例，合并高血压12例。肿瘤直径3.4～15 cm、平均7.6 cm；腺癌37例，鳞癌9例；临床分期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。排除标准：①接受其他药物化疗者；②化疗期间或者以前接受过放疗者；③化疗前已有心脏系统疾病者；④伴有其他系统疾病者。

1.2新辅助化疗方法卡铂、紫杉醇各50 mg/m2静滴，每周1次，治疗5周。

1.3心脏功能观察方法每例患者化疗前后计数心率，用校准后的台式血压计测量收缩压及舒张压，抽取空腹静脉测血清肌酸激酶、肌酸激酶同工酶、脑钠肽和肌钙蛋白，行心脏彩超检查测左心室收缩末容积、左心室舒张末容积、左心室射血分数、左心室容量、下腔静脉血流速度。

1.4统计学方法采用STATA11.0统计软件。对化疗后各指标变化行单因素Logistic回归分析，并计算变化值和95%可信区间(95%CI)。P<0.05为差异有统计学意义。

2结果

46例食管癌患者接受卡铂联合紫杉醇新辅助化疗5周后收缩压平均下降18 mmHg，95%CI为(-25,-10),P<0.05；舒张压平均下降6 mmHg，95%CI为(-14，-2),P<0.05；心率平均增加5次/min，95%CI为(1，11) ,P<0.05；血清肌钙蛋白平均升高0.008 mmol/L,95%CI为(-0.002，-0.012),P<0.05；血清肌酸激酶平均升高42 IU/L，95%CI为(18，71),P<0.05；左心室容量平均下降54 mL，95%CI为(-72，-39)，P<0.05。血清肌酸激酶同工酶平均升高0.2 mmol/L, 95%CI为(0.1，0.7)，P=0.16；血清脑钠肽平均升高4 mmol/L,95%CI为(-15,22)，P=0.07；左心室收缩末容积平均下降3 mL,95%CI为(-8,5),P=0.613；左心室舒张末容积平均下降8 mL,95%CI为(-16,4)，P=0.172；下腔静脉血流速度平均增加6 m/s,95%CI为(2,-12),P=0.072。

3讨论

食管癌手术较大，术前需要综合评估患者的耐受程度。本研究结果显示，接受卡铂联合紫杉醇新辅助化疗的患者，收缩压及舒张压降低，心率升高，说明新辅助化疗患者血容量有所降低，并出现心率加快以代偿心室容量降低。如果血压持续降低,必将影响冠状动脉的血流，从而影响心肌舒张期的供血，短期可引起心肌损害并出现心肌酶谱的改变，长时间心肌损害则可以引起心脏的代偿性改变，导致心衰甚至心源性猝死[6]。

本研究结果显示，5周新辅助化疗后患者收缩压降低的95%CI为10～25 mmHg。有报道称，新辅助化疗药物对服用高血压药物的患者收缩压影响更大，特别是使用α受体阻断剂的患者，其收缩压下降更显著[7]。5-FU联合顺铂治疗食管癌有可能会导致心律失常、心绞痛、心肌梗死、心衰，甚至猝死[8]。此方案的心脏毒性最大可能是来自铂类药物，一项铂类联合其他药物治疗睾丸癌转移的研究中也发现其存在心肌损害[9，10]。紫杉醇的心肌损害主要为心动过缓，其导致心衰的风险也不容忽视[11,12]。本研究结果显示，患者化疗5周后血清肌钙蛋白平均升高0.008 mmol/L,肌酸激酶升高42 U/L，说明接受新辅助化疗的患者血清心肌酶谱明显发生了改变，心脏受损。左心室负责为全身器官供血，左心室射血分数如果低于50%表示左心室功能明显受到了损害。患者虽不出现临床症状，但其储备功能已经不足，不能耐受手术治疗[13~15]。本组患者接受卡铂、紫杉醇联合新辅助化疗5周后,心脏射血分数有所降低，虽然没有统计学意义，不过我们化疗的疗程短，随访时间也短，尚不能说明新辅助化疗对食管癌患者的心室功能没有影响。

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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)

中图分类号：R735.1

文献标志码：A

文章编号：1002-266X(2016)06-0007-03

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

作者简介：第一王庭丰(1985-),男,本科,医师,主要研究方向为肿瘤化疗基础与临床。E-mail: wantingfeng1233@qq.com

基金项目：国家自然科学基金青年基金资助项目(81201881)。