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长期使用大剂量累积的聚乙二醇化脂质体阿霉素未出现心脏毒性。

Absence of cardiotoxicity with prolonged treatment and large accumulating doses of pegylated liposomal doxorubicin.

作者信息

Blank N, Laskov I, Kessous R, Kogan L, Lau S, Sebag I A, Gotlieb Walter H, Rudski L

机构信息

Division of Cardiology, Jewish General Hospital, McGill University, Montreal, QC, Canada.

Division of Gynecologic Oncology, McGill University SMBD Jewish General Hospital, 3755 Chemin de la Cote-Ste-Catherine, Montreal, QC, H3T 1E2, Canada.

出版信息

Cancer Chemother Pharmacol. 2017 Oct;80(4):737-743. doi: 10.1007/s00280-017-3412-8. Epub 2017 Aug 11.

Abstract

BACKGROUND

Pegylated liposomal doxorubicin (PLD) is used as a second-line therapy for gynecologic cancers, with a better short-term toxicity profile compared to doxorubicin or other anthracyclines.

METHODS

We screened 14 patients with recurrent gynecologic cancers, who underwent prolonged treatment with large cumulative doses of PLD for overt or subtle signs of cardiotoxicity (CTX) using standard and advanced echocardiography techniques [3D volumetric method for left ventricular ejection fraction (LVEF) and left ventricular/right ventricular global longitudinal strain]. Half the patients had previous echocardiographic studies available for comparison.

RESULTS

The average PLD treatment duration was 23.6 ± 10.8 months (range 13-57), accumulating dose of 1387 ± 483 mg (range 780-2538 mg). The study group had a normal LVEF both by 2D-echo (60 ± 5%, range 50-67) and 3D echo (58 ± 5%, range 46-63). Two patients (14%) were found to have minimally reduced ejection fraction by 2D and 3D echo (50%/46% and 51%/49%, respectively) that did not meet the current definition of CTX. For the seven patients who had consecutive echocardiography studies, the average LVEF remained stable between studies (59 ± 7, 60 ± 9 and 58 ± 10.5% for the latest study, previous, p < 0.79, and most remote study p < 0.9); No change was found in average left ventricular/right ventricular global longitudinal strain as well: -20.8 ± 4.6% at the latest study and -19.3 ± 2.6% for the previous (p < 0.51).

CONCLUSION

No prevalent or incident cases of cardiotoxicity were found despite prolonged treatment with large cumulative doses of PLD, adding to previous reports on shorter treatment duration.

摘要

背景

聚乙二醇化脂质体阿霉素(PLD)用作妇科癌症的二线治疗药物,与阿霉素或其他蒽环类药物相比,其短期毒性反应较小。

方法

我们筛选了14例复发性妇科癌症患者,这些患者接受了大累积剂量PLD的长期治疗,使用标准和先进的超声心动图技术[左心室射血分数(LVEF)和左心室/右心室整体纵向应变的三维容积法]检测明显或细微的心脏毒性(CTX)迹象。一半患者有先前的超声心动图研究结果可供比较。

结果

PLD的平均治疗持续时间为23.6±10.8个月(范围13 - 57个月),累积剂量为1387±483毫克(范围780 - 2538毫克)。研究组通过二维超声心动图测得的LVEF正常(60±5%,范围50 - 67%),三维超声心动图测得的LVEF也正常(58±5%,范围46 - 63%)。两名患者(14%)通过二维和三维超声心动图测得射血分数略有降低(分别为50%/46%和51%/49%),但不符合当前CTX的定义。对于7例进行了连续超声心动图检查的患者,各次检查之间的平均LVEF保持稳定(最新检查为59±7%,上次检查为60±9%,最早检查为58±10.5%,p < 0.79);左心室/右心室整体纵向应变的平均值也未发现变化:最新检查时为 - 20.8±4.6%,上次检查时为 - 19.3±2.6%(p < 0.51)。

结论

尽管接受了大累积剂量PLD的长期治疗,但未发现普遍或新发的心脏毒性病例,这与之前关于较短治疗持续时间的报道一致。

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