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目的:观察分析新型癌细胞诱导分化剂二乙酰己二胺(CAHB)对骨髓增生异常综合征(MDS)患者心电图的影响。方法:MDS患者48例序贯进入I期临床耐受性试验、单次给药药动学研究、多剂量给药的耐受性和药动学研究;MDS患者10例,进入ⅡA期临床试验。用药前、中、后进行十二导联心电图监测。结果:I期临床试验的48例患者完成全部试验,用药后出现心电图异常改变的有9例,包括偶发室性心律失常1例、T波改变3例、ST-T改变3例和左心室高电压2例,但均无不适主诉,也未予治疗,在停药后观察期内恢复正常。未观察到QT间期或QTc的延长。ⅡA期临床试验的10例患者共完成18个疗程治疗,有2例观察到心电图心室除极和复极的相关性变化,包括出现U波(使QT时间延长)、ST段压低、T波低平、钝挫等,第二疗程时又重现上述改变。但不伴有胸闷、气急等不适症状,也无相应的心肌损伤标志物的异常升高、电解质异常、超声心动图和动态心电图的特异性改变,心电图的异常在停药后6 d内消失。结论:心电图的异常改变与本试验药物相关,但停药后可恢复,且不伴有其他心脏安全性指标的相应变化。
OBJECTIVE: To observe the effect of a new type of cancer-inducing differentiation agent, diacetylhexamethylenediamine (CAHB), on electrocardiogram in patients with myelodysplastic syndrome (MDS). Methods: Forty-eight patients with MDS were included in phase I clinical trials, single-dose pharmacokinetic study, multi-dose tolerability and pharmacokinetics study. Ten patients with MDS were enrolled in Phase IIA clinical trial . Before, during and after the twelve lead ECG. RESULTS: All 48 patients in phase I trial completed all of the trials. Nine patients had abnormal electrocardiogram (ECG) after treatment, including 1 incidental ventricular arrhythmia, 3 cases of T wave change, 3 cases of ST-T changes and left ventricular hypertrophy Voltage in 2 cases, but no discomfort complaint, nor treatment, after stopping the observation period returned to normal. No QT interval or QTc extension was observed. A total of 18 courses of treatment were performed in 10 patients in stage IIA clinical trials, and 2 cases of ECG-related changes in ventricular depolarization and repolarization were observed including U wave (prolonging QT time), ST depression, low T wave Flat, blunt, etc., the second course of treatment to reproduce the above changes. But not accompanied by chest tightness, shortness of breath and other symptoms, there is no corresponding abnormalities of myocardial injury markers, electrolyte abnormalities, echocardiography and Holter ECG changes, ECG abnormalities disappear within 6 d after stopping. Conclusion: The abnormal changes of electrocardiogram are related to the test drug, but can be recovered after stopping the drug without the corresponding changes of other cardiac safety indexes.