The effect of medical and urologic disorders on the survival of patients with metastatic castration resistant prostate cancer treated with abiraterone or enzalutamide

Abstract

Introduction: Androgenic deprivation therapies have been linked to the development of metabolic syndrome (MS) and cardiovascular diseases, which may lead to a poorer survival in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC). We aimed to analyze whether some cardiovascular or neurological disorders, together with other medical and urological complications, may have an effect on survival outcomes, at baseline and during treatment from patients treated with androgen pathway inhibitors (API). Material and Methods: A retrospective study of a consecutive series of patients diagnosed with mCRPC between 2010 and 2018 treated with API in the first line setting in a single center. Results: Seventy-three patients met the inclusion criteria. Baseline prognostic factors associated with worse survival were diabetes mellitus (DM) with insulin needs compared to patients without DM [hazard ratio (HR) = 0.19, p = 0.025], hypertension (HTN) (HR = 0.46, p = 0.035), and a history of stroke (HR = 0.16, p < 0.001). However, previous history of hypercholesterolemia, arrythmias, and cognitive disorders did not result in a significant worsening on survival. During treatment, patients who developed de novo HTN had the best progression free survival (PFS) (HR = 0.38, p = 0.048) and overall survival (OS) (HR 0.08, p = 0.012) compared with patients with previous HTN. Other factors related to worse outcomes included the presence of heart failure (HR = 0.31, p = 0.001), the requirement for major opioids for pain relief (HR = 0.33, p = 0.023), and the presence of bilateral ureterohydronephrosis (HR = 0.12, p = 0.008). Conclusions: Some comorbidities may be strongly involved in patient outcomes when receiving API for mCRPC. In this sense, collaborative networking between specialists and caregivers treating prostate cancer (PC) patients should be recommended, focusing on MS features, cardiovascular and neurological disorders in order to anticipate medical and surgical complications.

A new method to quantify the effect of co-medication on the efficacy of abiraterone in metastatic castration-resistant prostate cancer patients

“…One study ( Benoist et al, 2018 ) strongly recommended to replace carbamazepine (DS = −5) during AA treatment. In addition, among the other drugs with negative DS, insulin (−3) and spironolactone (−1) have also been shown to impair the efficacy of AA treatment ( Serrano Domingo et al, 2021 ; Vicente-Valor et al, 2021 ). The positive effect present in our study of frequently used drugs with positive DS, like vitamin D (5) and pantoprazole (5), which is a proton pump inhibitor (PPI), should be emphasized.…”

Cardiovascular events among patients with prostate cancer treated with abiraterone and enzalutamide

“…Androgen deprivation therapy (ADT) is central to treating locally advanced and metastatic disease [7] by blocking the production of testosterone or curtailing its function to stop prostate cancer growth. Abiraterone acetate (AA), an androgen biosynthesis inhibitor, and enzalutamide (ENZ), an androgen receptor signalling inhibitor, are standard hormonal therapies that are mainstay additions to ADT.…”

“…Real-world studies showing the association between cardiovascular events related to hormonal treatments and preexisting metabolic, cardiovascular, or neurological conditions are limited [7,10,[15][16][17]. Furthermore, because differential adverse effects of AA and ENZ and their interactions with patient comorbidities have not been fully elucidated, there is little guidance on how to choose these drugs based on pre-existing conditions [10].…”

Outcomes Following Abiraterone versus Enzalutamide for Prostate Cancer: A Scoping Review

“…Importantly, adverse drug effects (ADEs) are common with NHTs and may vary with patient and drug characteristics [ 8 ]. Limited real-world studies have shown associations between NHT toxicities and pre-existing metabolic, cardiovascular, or neurological conditions [ 12 , 13 ]. For instance, AA has been shown to significantly increase cardiomyopathy while ENZ increases hypertension [ 11 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”