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

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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.

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Acknowledgements

This work was made possible in part by Grants from the Montreal-Israel Cancer Research Foundation, the Gloria Shapiro fund, the Hospital Foundation, and the Levy Family Fund.

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Author notes

  1. N. Blank and I. Laskov: equal contributors.

Authors and Affiliations

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

    N. Blank, I. A. Sebag & L. Rudski

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

    I. Laskov, R. Kessous, L. Kogan, S. Lau & Walter H. Gotlieb

  3. Department of Obstetrics and Gynecology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    I. Laskov

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  1. N. Blank
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Correspondence to Walter H. Gotlieb.

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The authors declare that they have no conflict of interest.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

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Informed consent was obtained from all individual participants included in the study.

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Blank, N., Laskov, I., Kessous, R. et al. Absence of cardiotoxicity with prolonged treatment and large accumulating doses of pegylated liposomal doxorubicin. Cancer Chemother Pharmacol 80, 737–743 (2017). https://doi.org/10.1007/s00280-017-3412-8

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  • DOI: https://doi.org/10.1007/s00280-017-3412-8

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