Skubitz Keith M, Blaes Anne H, Konety Suma H, Francis Gary S
Department of Medicine, The University of Minnesota Medical School, Box 286, University Hospital, Minneapolis, MN, 55455, USA.
Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN, USA.
Cancer Chemother Pharmacol. 2017 Oct;80(4):787-798. doi: 10.1007/s00280-017-3420-8. Epub 2017 Aug 30.
One of the great conundrums for both oncologists and cardiologists is how to best monitor the potential and actual cardiotoxicity of doxorubicin. Pegylated-liposomal doxorubicin (PLD) has a safer cardiotoxicity profile than bolus administration of doxorubicin. Although ejection fraction (EF) is commonly performed to monitor doxorubicin-induced cardiotoxicity, evidence for its predictive utility is limited. We examined the incidence of doxorubicin-induced heart failure (HF) in patients who received a large cumulative dose of doxorubicin as PLD and its relation to EF and HF.
A retrospective chart review of patients who received a large cumulative dose of PLD, sometimes after previous free doxorubicin treatment, was performed to examine the incidence of doxorubicin-induced heart failure (HF) and its relation to EF and development of HF.
No definite doxorubicin-induced clinical HF was observed among 56 patients (median age 54; 15-93) who received a cumulative doxorubicin dose (free + PLD) of >450 mg/m. Of these, 49 received >500 mg/m, 28 > 700 mg/m, 19 > 800 mg/m, 14 > 1000 mg/m, and 5 > 1400 mg/m. The EF varied greatly over time in some patients treated with PLD in the absence of symptoms or signs of heart failure, and was not particularly useful in making decisions regarding further dosing.
Pegylated-liposomal doxorubicin was associated with a low risk of doxorubicin-induced HF in a retrospective cohort of patients receiving large cumulative doses of doxorubicin and long-term follow-up. EF did not predict doxorubicin-induced cardiotoxicity in our cohort of adult patients receiving PLD. Given the lack of prognostic clarity regarding modest EF changes, regular EF monitoring may not be warranted, at least when PLD is used in adults. Modest changes in EF should probably not be used to limit a patient's access to PLD, but may warrant cardiology consultation for long-term follow-up after completion of therapy.
肿瘤学家和心脏病学家面临的一大难题是如何最好地监测多柔比星的潜在和实际心脏毒性。聚乙二醇化脂质体多柔比星（PLD）的心脏毒性比静脉推注多柔比星更安全。虽然射血分数（EF）通常用于监测多柔比星诱导的心脏毒性，但其预测效用的证据有限。我们研究了接受大累积剂量PLD多柔比星治疗的患者中多柔比星诱导的心力衰竭（HF）的发生率及其与EF和HF的关系。
对接受大累积剂量PLD（有时在先前接受游离多柔比星治疗后）的患者进行回顾性病历审查，以研究多柔比星诱导的心力衰竭（HF）的发生率及其与EF和HF发生的关系。
在56例（中位年龄54岁；15 - 93岁）接受多柔比星累积剂量（游离+PLD）>450mg/m²的患者中，未观察到明确的多柔比星诱导的临床HF。其中，49例接受剂量>500mg/m²，28例>700mg/m²，19例>800mg/m²，14例>1000mg/m²，5例>1400mg/m²。在一些接受PLD治疗且无心力衰竭症状或体征的患者中，EF随时间变化很大，在决定进一步给药方面并非特别有用。
在接受大累积剂量多柔比星并进行长期随访的回顾性队列患者中，聚乙二醇化脂质体多柔比星与多柔比星诱导的HF风险较低相关。在我们接受PLD治疗的成年患者队列中，EF不能预测多柔比星诱导的心脏毒性。鉴于EF适度变化的预后不明确，至少在成人使用PLD时，可能无需定期进行EF监测。EF的适度变化可能不应被用于限制患者使用PLD，但可能需要在治疗完成后进行长期随访时咨询心脏病专家。
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