Evolution of Electrocardiographic Repolarization Parameters During Antiandrogen Therapy in Patients with Prostate Cancer and Hypogonadism

Cardiovasc Toxicol. 2020 Aug;20(4):390-400. doi: 10.1007/s12012-020-09566-6.

Abstract

We assessed the effects of antiandrogen therapy on ECG parameters of ventricular repolarization related to arrhythmic risk in 35 patients aged 70.3 ± 7 years with advanced prostate cancer treated with degarelix associated with enzalutamide (group A, 26 patients) or degarelix monotherapy (group B, 9 patients). We analyzed Fridericia corrected Q-T interval (QTc), Q-T dispersion (QTd), J-Tpeak interval (JTp), mean and maximum Tpeak-Tend interval (Tpe) and Tpe/QT ratio, Tpeak-Tend dispersion (Tped), index of cardio-electrophysiological balance (iCEB) from ECG tracings, and occurrence of ventricular premature beats (VPB) recorded by Holter ECG, before initiation of medication (M0) and after 6 months of treatment (M1). The groups had similar demographics except for a higher prevalence of prior myocardial infarction in group B (p = 0.01). All patients had low serum testosterone at M1. Baseline QTc, QTd, maxTpe/QT, meanTpe, maxTpe, Tped values were higher in B compared to A. They had a significant prolongation at M1 only in A. 20 patients in A and 6 in B had a 10% prolongation or decrease of iCEB (p = 0.66). In 5 patients, VPB severity increased from non-complex to complex: 3 in A and 2 in B (p = 0.31), but no sustained ventricular arrhythmia was registered. In conclusion, after 6 months of treatment, patients with hypogonadism on degarelix associated with enzalutamide had significant prolongation of QTc, QTd, maxTpe, meanTpe/QT, maxTpe/QT, Tped compared to patients on degarelix alone. The proportion of patients with 10% iCEB variation was similar between groups. There was no record of severe arrhythmias during the first 6 months of treatment.

Keywords: Degarelix; Enzalutamide; Hypogonadism; QT interval; Tpeak-tend wave interval.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Aged
  • Androgen Antagonists / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Arrhythmias, Cardiac / chemically induced*
  • Arrhythmias, Cardiac / diagnosis
  • Arrhythmias, Cardiac / physiopathology
  • Benzamides
  • Electrocardiography
  • Heart Conduction System / drug effects*
  • Heart Conduction System / physiopathology
  • Heart Rate / drug effects
  • Humans
  • Hypogonadism / chemically induced*
  • Hypogonadism / diagnosis
  • Hypogonadism / physiopathology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Nitriles
  • Oligopeptides / adverse effects*
  • Phenylthiohydantoin / adverse effects
  • Phenylthiohydantoin / analogs & derivatives*
  • Prospective Studies
  • Prostatic Neoplasms / drug therapy*
  • Risk Assessment
  • Risk Factors
  • Time Factors

Substances

  • Androgen Antagonists
  • Benzamides
  • Nitriles
  • Oligopeptides
  • acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide
  • Phenylthiohydantoin
  • enzalutamide