Department of Cardiology, Saint-Antoine University and Medical School, Paris, France.
Invest New Drugs. 2012 Apr;30(2):611-5. doi: 10.1007/s10637-010-9546-8. Epub 2010 Oct 6.
Cardiotoxicity of molecular targeted therapies (MTT) is poorly understood and is being investigated among patients with metastatic solid tumours. The frequency of cardiac events among patients receiving MTT has been evaluated in various ways, particularly troponin elevations.
We prospectively evaluated cardiotoxicity among patients included in Phase 1 trials receiving molecular targeted therapies (MTT) for a metastatic solid tumour. At baseline, all patients were examined before the first cycle and monitored including a clinical examination, ECG and troponin I measurement. A trans-thoracic echocardiography was performed at baseline and before each cycle. Patients were enrolled in different trials investigating : an anti-VEGF monoclonal antibody, anti-VEGFR tyrosine kinase inhibitors, and a kinesin inhibitor.
Among the 90 patients evaluated, 10 (11%) experienced chest pain and troponin I elevation (n = 2,20%) or asymptomatic troponin I elevation (n = 8, 80%) during follow-up. All patients were re-evaluated at the time of symptoms or troponin I elevation with trans-thoracic echocardiography, cardiac magnetic resonance and coronary angiography. All except one patient, had a normal LVEF during their re-evaluation. One patient exhibited ECG changes (T wave inversion). No QTc interval prolongation was found. On cardiac magnetic resonance, no late gadolinium myocardial enhancement was observed. All coronary angiographies were normal (no occlusion, or coronary stenosis >50%). All patients received beta blockers and aspirin. All Patients were re-challenged with the study drug and no cardiotoxicity was observed during follow up.
Troponin elevations are frequent among patients receiving molecular targeted therapies. Re-challenging these patients after a careful evaluation and under medical treatment seems to be possible. The mechanism underlying troponin elevations does not seem to be associated with coronary occlusion nor with toxic myocarditis.
分子靶向治疗（MTT）的心脏毒性尚未被充分了解，目前正在转移性实体瘤患者中进行研究。通过各种方法评估了接受 MTT 的患者中心脏事件的发生率，尤其是肌钙蛋白升高。
我们前瞻性评估了接受转移性实体瘤 MTT 的 1 期临床试验患者的心脏毒性。在基线时，所有患者在第一周期前接受检查，并进行监测，包括临床检查、心电图和肌钙蛋白 I 测量。在基线和每个周期前进行经胸超声心动图检查。患者入组不同的试验，研究对象包括抗 VEGF 单克隆抗体、抗 VEGFR 酪氨酸激酶抑制剂和驱动蛋白抑制剂。
在 90 例接受评估的患者中，10 例（11%）在随访期间出现胸痛和肌钙蛋白 I 升高（n=2，20%）或无症状肌钙蛋白 I 升高（n=8，80%）。所有患者在出现症状或肌钙蛋白 I 升高时均接受经胸超声心动图、心脏磁共振和冠状动脉造影检查。除 1 例患者外，所有患者在重新评估时 LVEF 均正常。1 例患者出现心电图改变（T 波倒置）。未发现 QTc 间期延长。心脏磁共振未观察到晚期钆增强心肌强化。所有冠状动脉造影均正常（无闭塞或冠状动脉狭窄>50%）。所有患者接受β受体阻滞剂和阿司匹林治疗。所有患者重新接受研究药物治疗，在随访期间未观察到心脏毒性。
接受分子靶向治疗的患者肌钙蛋白升高较为常见。在仔细评估和药物治疗后重新对这些患者进行治疗似乎是可行的。肌钙蛋白升高的机制似乎与冠状动脉闭塞或中毒性心肌炎无关。
