Division of Hematology/Oncology, Department of Medicine, University of Florida, 1600 SW Archer Rd., PO Box 100277, Gainesville, FL, 32610, USA.
Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Cardiovasc Toxicol. 2018 Apr;18(2):184-191. doi: 10.1007/s12012-017-9429-8.
Our aim is to study unanticipated cardiotoxicity associated with the use of anticancer targeted agents, a problem that remains poorly understood. Using diagnosis codes, we retrospectively identified patients with both hematologic malignancies (HM) and cardiovascular diseases (n = 820 patients). Cardiotoxicity was defined per published criteria. The targeted agents of interest included tyrosine kinase inhibitors, proteasome inhibitors, monoclonal antibodies, and immunomodulatory agents. Patients found with cardiotoxicity (n = 29) were compared with 70 case-matched reference subjects. Median time from targeted therapy exposure to cardiotoxicity was 132 days. A higher percentage of patients had prior exposure to anthracyclines in study versus reference group (65.5 vs. 42.8%, P = 0.04), however, did not stay significant in multivariate analysis. Two variables were significant predictors, prior of DVT/PE and Karnofsky score of ≥ 80% (P ≤ 0.011). Only 2 study group patients died of cardiac causes. Most cardiotoxicity patients (23/29) had remained stable or improved, while 21 patients received further chemotherapy. OS was lower in the study group (P = 0.018) versus the reference group. In conclusion, a small number patients with HM experience unanticipated cardiotoxicity with low related mortality. Risk of cardiotoxicity was significantly associated with history of DVT/PE. Most patients do well, but despite that, their OS is significantly poorer.
我们的目的是研究与使用抗癌靶向药物相关的意外心脏毒性，这一问题仍未得到充分理解。我们使用诊断代码回顾性地确定了同时患有血液系统恶性肿瘤（HM）和心血管疾病（n=820 例患者）的患者。按照已发表的标准定义心脏毒性。感兴趣的靶向药物包括酪氨酸激酶抑制剂、蛋白酶体抑制剂、单克隆抗体和免疫调节剂。患有心脏毒性的患者（n=29）与 70 名匹配的参考患者进行比较。从靶向治疗暴露到心脏毒性的中位时间为 132 天。与对照组相比，研究组中有更高比例的患者先前接受过蒽环类药物治疗（65.5%比 42.8%，P=0.04），但在多变量分析中无统计学意义。两个变量是显著的预测因素，先前的 DVT/PE 和 Karnofsky 评分≥80%（P≤0.011）。只有 2 名研究组患者死于心脏原因。大多数心脏毒性患者（23/29）病情稳定或改善，而 21 名患者接受了进一步的化疗。研究组的 OS 明显低于对照组（P=0.018）。总之，少数 HM 患者会发生意外的心脏毒性，但相关死亡率较低。心脏毒性的风险与 DVT/PE 病史显著相关。大多数患者情况良好，但尽管如此，他们的 OS 仍明显较差。
