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舒尼替尼治疗转移性肾细胞癌后的心血管毒性:一项多中心分析。

Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis.

作者信息

Di Lorenzo G, Autorino R, Bruni G, Cartenì G, Ricevuto E, Tudini M, Ficorella C, Romano C, Aieta M, Giordano A, Giuliano M, Gonnella A, De Nunzio C, Rizzo M, Montesarchio V, Ewer M, De Placido S

机构信息

Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli.

Clinica Urologica, Seconda Università degli Studi, Napoli.

出版信息

Ann Oncol. 2009 Sep;20(9):1535-1542. doi: 10.1093/annonc/mdp025. Epub 2009 May 27.

Abstract

BACKGROUND

Recent data have shown that cardiotoxicity represents a potentially important side-effect in patients treated with sunitinib. We reviewed cardiac adverse events in patients with metastatic renal cell carcinoma (RCC) who underwent treatment with this agent.

PATIENTS AND METHODS

The medical records of 175 patients with metastatic RCC treated with sunitinib at eight Italian institutions were retrospectively reviewed. Alterations in left ventricular ejection fraction (LVEF) and blood pressure were evaluated. Patients with preexisting cardiac risk factors were specifically scrutinized for increased expression of cardiac changes.

RESULTS

Grade 3 hypertension was seen in 17 patients (9.7%); in 12 of these 17, hypertension developed after receiving the third sunitinib cycle. Among these 17 patients, 12 (70.6%) also experienced left ventricular systolic (LVEF) dysfunction; in all, 33 of the 175 patients (18.9%) developed some degree of cardiac abnormality, of which 12 were classified as grade 3 LVEF dysfunction and/or congestive heart failure (CHF) (6.9%). Significant univariate associations for predictors of CHF were history of hypertension (P = 0.008), history of coronary heart disease (P = 0.0005) and prior treatment with an angiotensin-converting enzyme inhibitor (P = 0.04). Multivariate analysis suggested that a history of coronary artery disease [odds ratio (OR) 18, 95% confidence interval (CI) 4-160, P = 0.005] and hypertension (OR 3, 95% CI 1.5-80, P = 0.04) was the only significant independent predictors of CHF.

CONCLUSIONS

Patients undergoing sunitinib, especially those with a previous history of hypertension and coronary heart disease, are at increased risk for cardiovascular events and should be monitored for exacerbations of their hypertension and for evidence of LVEF dysfunction during treatment.

摘要

背景

近期数据显示,心脏毒性是接受舒尼替尼治疗患者中一种潜在的重要副作用。我们回顾了接受该药物治疗的转移性肾细胞癌(RCC)患者的心脏不良事件。

患者与方法

回顾性分析了意大利8家机构中175例接受舒尼替尼治疗的转移性RCC患者的病历。评估左心室射血分数(LVEF)和血压的变化。对存在心脏危险因素的患者进行了特别检查,以观察心脏变化的增加情况。

结果

17例患者(9.7%)出现3级高血压;在这17例患者中,12例在接受第三个舒尼替尼周期后出现高血压。在这17例患者中,12例(70.6%)还出现左心室收缩功能障碍(LVEF);总共175例患者中有33例(18.9%)出现了某种程度的心脏异常,其中12例被归类为3级LVEF功能障碍和/或充血性心力衰竭(CHF)(6.9%)。CHF预测因素的显著单因素关联包括高血压病史(P = 0.008)、冠心病病史(P = 0.0005)和既往使用血管紧张素转换酶抑制剂治疗(P = 0.04)。多因素分析表明,冠心病病史[比值比(OR)18,95%置信区间(CI)4 - 160,P = 0.005]和高血压(OR 3,95% CI 1.5 - 80,P = 0.04)是CHF仅有的显著独立预测因素。

结论

接受舒尼替尼治疗的患者,尤其是有高血压和冠心病病史的患者,发生心血管事件的风险增加,在治疗期间应监测其高血压的加重情况以及LVEF功能障碍的证据。

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