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

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.

Keywords: Cardiotoxicity; Echocardiography; Gynecologic cancers; Pegylated liposomal doxorubicin.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / adverse effects
  • Cardiotoxicity / epidemiology*
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives*
  • Echocardiography / methods
  • Female
  • Genital Neoplasms, Female / drug therapy*
  • Genital Neoplasms, Female / pathology
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Pilot Projects
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects
  • Retrospective Studies
  • Time Factors
  • Ventricular Function, Left / drug effects

Substances

  • Antibiotics, Antineoplastic
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin