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Cancer Chemotherapy and Pharmacology

, Volume 80, Issue 4, pp 787–798 | Cite as

Cardiac safety profile of patients receiving high cumulative doses of pegylated-liposomal doxorubicin: use of left ventricular ejection fraction is of unproven value

  • Keith M. SkubitzEmail author
  • Anne H. Blaes
  • Suma H. Konety
  • Gary S. Francis
Original Article

Abstract

Purpose

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.

Methods

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.

Results

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/m2. Of these, 49 received >500 mg/m2, 28 > 700 mg/m2, 19 > 800 mg/m2, 14 > 1000 mg/m2, and 5 > 1400 mg/m2. 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.

Conclusions

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.

Keywords

Anthracycline Cardiotoxicity Cardio-oncology Ejection fraction Heart failure Pegylated-liposomal doxorubicin 

Notes

Compliance and ethical standards

Funding

This study received no funding.

Conflict of interest

Dr. Skubitz has received research funding from Johnson & Johnson or its subsidiaries and has owned publicly traded stock in JNJ in the past. The other authors have no potential conflict.

Ethical standards

This study was approved by the University of Minnesota IRB and was performed in accordance with the ethical standards of the institutional IRB and the 1964 Helsinki declaration and its later amendments.

Human and animal rights

This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was not obtained, per the approval of the University of Minnesota IRB, as it was a retrospective study, no identifying information is presented, and many of the patients are no longer living.

Supplementary material

280_2017_3420_MOESM1_ESM.docx (43 kb)
Supplementary material 1 (DOCX 43 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of MedicineThe University of Minnesota Medical SchoolMinneapolisUSA
  2. 2.Masonic Cancer Center, University of Minnesota Medical SchoolMinneapolisUSA

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