Safety of Abiraterone Acetate in Castration-resistant Prostate Cancer Patients With Concomitant Cardiovascular Risk Factors

Procopio, Giuseppe; Grassi, Paolo; Testa, Isabella; Verzoni, Elena; Torri, Valter; Salvioni, Roberto; Valdagni, Riccardo; Braud, Filippo de

doi:10.1097/coc.0b013e3182a790ce

Cited by 25 publications

(21 citation statements)

References 21 publications

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“…A recent observational study conducted in Italy showed the cardiac safety of abiraterone acetate [22]. Our different findings may be explained by subtle differences in the patient population in terms of higher cardiovascular risk and prior use of ketoconazole, which was used in two out of five patients who had a cardiac SAE.…”

Section: Discussionmentioning

confidence: 57%

Association of Biomarkers with Serious Cardiac Adverse Events during Abiraterone Acetate Treatment in Castration Resistant Prostate Cancer

Campora

Campazzi

Zanardi

et al. 2016

Translational Oncology

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BACKGROUND: Abiraterone acetate is an effective drug for castration-resistant prostate cancer, but cardiac serious adverse events (SAEs) may occur. We studied their association with N-terminal pro–brain natriuretic peptide (NT-proBNP) and troponin T (TnT) during abiraterone therapy. PATIENTS AND METHODS: In a single institution, 17 patients were treated with abiraterone acetate 1 g daily with concomitant prednisone and then switched to dexametasone plus canrenone. Blood samples for PSA, NT-proBNP, and TnT were obtained at baseline and after 1, 3, and 6 months. RESULTS: Five patients (29.4%) experienced G3 to 4 cardiac SAEs after a median of 13 weeks (range, 9-32), including pulmonary edema, heart failure, acute coronary syndrome, sinus bradycardia with syncope, and pulmonary edema. At baseline, 4 weeks, and 3 months, median NT-proBNP and TnT levels were higher in patients with subsequent cardiac SAEs (P= .03 and P= .04 for NT-proBNP and TnT at 3 months, respectively). After switching to dexametasone and introducing canrenone, no additional cardiac SAEs were noted. Overall response rate was 67%. CONCLUSIONS: Our study suggests a higher than expected risk of cardiac SAEs during abiraterone treatment which may well be due to the small sample size and the unrestricted entry criteria. However, baseline and frequent NT-proBNP and TnT monitoring predicted a higher risk for cardiac SAE. Larger studies should confirm our findings.

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Section: Discussionmentioning

confidence: 57%

Association of Biomarkers with Serious Cardiac Adverse Events during Abiraterone Acetate Treatment in Castration Resistant Prostate Cancer

Campora

Campazzi

Zanardi

et al. 2016

Translational Oncology

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“…For patients with CRPC and concurrent cardiovascular comorbidities, these side-effects can pose added risks. The cardiovascular outcomes of abiraterone treatment in 51 patients with mCRPC with cardiovascular comorbidities treated with standard doses of abiraterone and prednisone were assessed 58. Comorbidities included controlled hypertension (41%), cardiac ischemia (14%), stroke (9%), dyslipidemia (18%) and hyperglycemia (30%).…”

Section: Effects Of Abiraterone On Quality Of Life and Specific Patiementioning

confidence: 99%

Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer

et al. 2014

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Suppression of gonadal testosterone synthesis represents the standard first line therapy for treatment of metastatic prostate cancer. However, in the majority of patients who develop castration-resistant prostate cancer (CRPC), it is possible to detect persistent activation of the androgen receptor (AR) through androgens produced in the adrenal gland or within the tumor itself. Abiraterone acetate was developed as an irreversible inhibitor of the dual functional cytochrome P450 enzyme CYP17 with activity as a 17α-hydroxylase and 17,20-lyase. CYP17 is necessary for production of nongonadal androgens from cholesterol. Regulatory approval of abiraterone in 2011, based on a phase III trial showing a significant improvement in overall survival (OS) with abiraterone and prednisone versus prednisone, represented proof of principle that targeting AR is essential for improving outcomes in men with CRPC. Inhibition of 17α-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone (ACTH), providing a rationale for development of CYP17 inhibitors with increased specificity for 17,20-lyase (orteronel, galeterone and VT-464) that can potentially be administered without exogenous corticosteroids. In this article, we review the development of abiraterone and other CYP17 inhibitors; recent studies with abiraterone that inform our understanding of clinical parameters such as drug effects on quality-of-life, potential early predictors of response, and optimal sequencing of abiraterone with respect to other agents; and results of translational studies providing insights into resistance mechanisms to CYP17 inhibitors leading to clinical trials with drug combinations designed to prolong abiraterone benefit or restore abiraterone activity.

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“…Full details of the study methods have been published previously [Procopio et al 2015]. Briefly, patients were ⩾18 years old, had received ⩾1 docetaxel-based regimen, their Eastern Cooperative Oncology group (ECOG) performance status (PS) was ⩽2 and their life expectancy was ⩾3 months.…”

Section: Methodsmentioning

confidence: 99%

Safety of long-term exposure to abiraterone acetate in patients with castration-resistant prostate cancer and concomitant cardiovascular risk factors

et al. 2016

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Background: We aimed to evaluate the long-term safety profile of abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) with controlled cardiovascular comorbidities or risk factors. Methods: We retrospectively analysed the clinical charts of consecutive mCRPC patients with cardiac disorders/risk factors who had been treated with abiraterone 1000 mg once daily plus prednisone 5 mg twice daily for a median duration of 16 months at an oncology referral centre between April 2011 and July 2015. Patients underwent an electrocardiogram (ECG) and echocardiographic assessments, including measurement of left ventricular ejection fraction (LVEF) at baseline and at the end of treatment. Blood pressure (BP) was measured daily at home. During follow up (median 24 months), all adverse events were recorded. Cardiac events (CEs) were defined, according to Common Terminology Criteria for Adverse Events version 4.0, as the appearance of a symptomatic CE that required medical intervention. Results: A total of 51 patients (median age 71 years) were evaluated. Pre-existing cardiovascular conditions included hypertension (41%), cardiac ischaemia (12%), stroke (9%), dyslipidaemia (18%) and type 2 diabetes mellitus (12%). No CEs were recorded and no changes in LVEF were observed. The most frequently reported adverse events were Grade 1-2 fluid retention (18%), hypertension (16%) and asthenia (16%). No patients permanently discontinued abiraterone due to cardiac events. Conclusions: Long-term abiraterone treatment was well tolerated in mCRPC patients with controlled cardiovascular comorbidities/risk factors, with no apparent worsening of cardiovascular conditions from baseline over an extended observation period.

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Safety of Abiraterone Acetate in Castration-resistant Prostate Cancer Patients With Concomitant Cardiovascular Risk Factors

Abstract: AA appears to be safe and well tolerated even in patients with cardiovascular comorbidities or with increased risk factors for cardiovascular diseases.

Cited by 25 publications

References 21 publications

Association of Biomarkers with Serious Cardiac Adverse Events during Abiraterone Acetate Treatment in Castration Resistant Prostate Cancer

Association of Biomarkers with Serious Cardiac Adverse Events during Abiraterone Acetate Treatment in Castration Resistant Prostate Cancer

Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer

Safety of long-term exposure to abiraterone acetate in patients with castration-resistant prostate cancer and concomitant cardiovascular risk factors

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