Statin Use and Survival in Patients with Metastatic Castration-resistant Prostate Cancer Treated with Abiraterone Acetate

Giuseppe Di Lorenzo, Guru Sonpavde, Gregory Pond, Giuseppe Lucarelli, Sabrina Rossetti, Gaetano Facchini, Sarah Scagliarini, Giacomo Cartenì, Piera Federico, Bruno Daniele, Franco Morelli, Teresa Bellelli, Matteo Ferro, Sabino De Placido, Carlo Buonerba

Research output: Contribution to journalArticle

Abstract

Background: Although statin use has been associated with favorable effects in various solid malignancies, no conclusive evidence is available at present. Statins are safe and inexpensive, and may synergize with novel antiandrogen agents abiraterone via pharmacokinetic interactions and decrease substrate availability for de novo androgen biosynthesis. Objective: To determine whether statin use affects survival in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. Design, setting, and participants: Medical records of patients with documented mCRPC between September 2011 and August 2016 were reviewed at multiple participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. A total of 187 patients receiving abiraterone for mCRPC between September 2011 and August 2016 were eligible for inclusion in this retrospective study. Outcome measurements and statistical analysis: Patients were assessed for overall survival (OS), statin use at the time of treatment initiation, prostate-specific antigen (PSA) variations, and other variables of interest. Univariable and multivariable analysis was used to explore the association of variables of interest with OS and PSA declines. Results and limitations: Statin use was a significant prognostic factor for longer OS in univariable (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.37-0.72; p <. 0.001) and multivariable analysis (HR 0.40, 95% CI 0.27-0.59; p <. 0.001) and was significantly associated with PSA declines (>50% decline at 12 wk: 72.1% in statin users vs 38.5% in non-users; p <. 0.001). Conclusions: Our study suggests a prognostic impact of statin use in patients receiving abiraterone for mCRPC. The mechanism of this interaction warrants elucidation, but may include enhancement of the antitumor activity of abiraterone as well as cardioprotective effects. Patient summary: We assessed the effects of statin use in patients with advanced prostate cancer receiving abiraterone. Patients treated with a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further studies assessing the use of abiraterone plus statins are warranted. Patients with advanced prostate cancer receiving a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further prospective studies are warranted.

Original languageEnglish
JournalEuropean Urology Focus
DOIs
Publication statusAccepted/In press - Jan 1 2017

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Castration
Prostatic Neoplasms
Survival
Prostate-Specific Antigen
Drug Interactions
Abiraterone Acetate
abiraterone
Antigenic Variation
Androgen Antagonists
Pharmaceutical Preparations
Androgens
Medical Records

Keywords

  • Abiraterone
  • Prostate cancer
  • Statins

ASJC Scopus subject areas

  • Urology

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Statin Use and Survival in Patients with Metastatic Castration-resistant Prostate Cancer Treated with Abiraterone Acetate. / Di Lorenzo, Giuseppe; Sonpavde, Guru; Pond, Gregory; Lucarelli, Giuseppe; Rossetti, Sabrina; Facchini, Gaetano; Scagliarini, Sarah; Cartenì, Giacomo; Federico, Piera; Daniele, Bruno; Morelli, Franco; Bellelli, Teresa; Ferro, Matteo; De Placido, Sabino; Buonerba, Carlo.

In: European Urology Focus, 01.01.2017.

Research output: Contribution to journalArticle

Di Lorenzo, Giuseppe ; Sonpavde, Guru ; Pond, Gregory ; Lucarelli, Giuseppe ; Rossetti, Sabrina ; Facchini, Gaetano ; Scagliarini, Sarah ; Cartenì, Giacomo ; Federico, Piera ; Daniele, Bruno ; Morelli, Franco ; Bellelli, Teresa ; Ferro, Matteo ; De Placido, Sabino ; Buonerba, Carlo. / Statin Use and Survival in Patients with Metastatic Castration-resistant Prostate Cancer Treated with Abiraterone Acetate. In: European Urology Focus. 2017.
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title = "Statin Use and Survival in Patients with Metastatic Castration-resistant Prostate Cancer Treated with Abiraterone Acetate",
abstract = "Background: Although statin use has been associated with favorable effects in various solid malignancies, no conclusive evidence is available at present. Statins are safe and inexpensive, and may synergize with novel antiandrogen agents abiraterone via pharmacokinetic interactions and decrease substrate availability for de novo androgen biosynthesis. Objective: To determine whether statin use affects survival in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. Design, setting, and participants: Medical records of patients with documented mCRPC between September 2011 and August 2016 were reviewed at multiple participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. A total of 187 patients receiving abiraterone for mCRPC between September 2011 and August 2016 were eligible for inclusion in this retrospective study. Outcome measurements and statistical analysis: Patients were assessed for overall survival (OS), statin use at the time of treatment initiation, prostate-specific antigen (PSA) variations, and other variables of interest. Univariable and multivariable analysis was used to explore the association of variables of interest with OS and PSA declines. Results and limitations: Statin use was a significant prognostic factor for longer OS in univariable (hazard ratio [HR] 0.51, 95{\%} confidence interval [CI] 0.37-0.72; p <. 0.001) and multivariable analysis (HR 0.40, 95{\%} CI 0.27-0.59; p <. 0.001) and was significantly associated with PSA declines (>50{\%} decline at 12 wk: 72.1{\%} in statin users vs 38.5{\%} in non-users; p <. 0.001). Conclusions: Our study suggests a prognostic impact of statin use in patients receiving abiraterone for mCRPC. The mechanism of this interaction warrants elucidation, but may include enhancement of the antitumor activity of abiraterone as well as cardioprotective effects. Patient summary: We assessed the effects of statin use in patients with advanced prostate cancer receiving abiraterone. Patients treated with a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further studies assessing the use of abiraterone plus statins are warranted. Patients with advanced prostate cancer receiving a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further prospective studies are warranted.",
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T1 - Statin Use and Survival in Patients with Metastatic Castration-resistant Prostate Cancer Treated with Abiraterone Acetate

AU - Di Lorenzo, Giuseppe

AU - Sonpavde, Guru

AU - Pond, Gregory

AU - Lucarelli, Giuseppe

AU - Rossetti, Sabrina

AU - Facchini, Gaetano

AU - Scagliarini, Sarah

AU - Cartenì, Giacomo

AU - Federico, Piera

AU - Daniele, Bruno

AU - Morelli, Franco

AU - Bellelli, Teresa

AU - Ferro, Matteo

AU - De Placido, Sabino

AU - Buonerba, Carlo

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: Although statin use has been associated with favorable effects in various solid malignancies, no conclusive evidence is available at present. Statins are safe and inexpensive, and may synergize with novel antiandrogen agents abiraterone via pharmacokinetic interactions and decrease substrate availability for de novo androgen biosynthesis. Objective: To determine whether statin use affects survival in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. Design, setting, and participants: Medical records of patients with documented mCRPC between September 2011 and August 2016 were reviewed at multiple participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. A total of 187 patients receiving abiraterone for mCRPC between September 2011 and August 2016 were eligible for inclusion in this retrospective study. Outcome measurements and statistical analysis: Patients were assessed for overall survival (OS), statin use at the time of treatment initiation, prostate-specific antigen (PSA) variations, and other variables of interest. Univariable and multivariable analysis was used to explore the association of variables of interest with OS and PSA declines. Results and limitations: Statin use was a significant prognostic factor for longer OS in univariable (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.37-0.72; p <. 0.001) and multivariable analysis (HR 0.40, 95% CI 0.27-0.59; p <. 0.001) and was significantly associated with PSA declines (>50% decline at 12 wk: 72.1% in statin users vs 38.5% in non-users; p <. 0.001). Conclusions: Our study suggests a prognostic impact of statin use in patients receiving abiraterone for mCRPC. The mechanism of this interaction warrants elucidation, but may include enhancement of the antitumor activity of abiraterone as well as cardioprotective effects. Patient summary: We assessed the effects of statin use in patients with advanced prostate cancer receiving abiraterone. Patients treated with a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further studies assessing the use of abiraterone plus statins are warranted. Patients with advanced prostate cancer receiving a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further prospective studies are warranted.

AB - Background: Although statin use has been associated with favorable effects in various solid malignancies, no conclusive evidence is available at present. Statins are safe and inexpensive, and may synergize with novel antiandrogen agents abiraterone via pharmacokinetic interactions and decrease substrate availability for de novo androgen biosynthesis. Objective: To determine whether statin use affects survival in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. Design, setting, and participants: Medical records of patients with documented mCRPC between September 2011 and August 2016 were reviewed at multiple participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. A total of 187 patients receiving abiraterone for mCRPC between September 2011 and August 2016 were eligible for inclusion in this retrospective study. Outcome measurements and statistical analysis: Patients were assessed for overall survival (OS), statin use at the time of treatment initiation, prostate-specific antigen (PSA) variations, and other variables of interest. Univariable and multivariable analysis was used to explore the association of variables of interest with OS and PSA declines. Results and limitations: Statin use was a significant prognostic factor for longer OS in univariable (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.37-0.72; p <. 0.001) and multivariable analysis (HR 0.40, 95% CI 0.27-0.59; p <. 0.001) and was significantly associated with PSA declines (>50% decline at 12 wk: 72.1% in statin users vs 38.5% in non-users; p <. 0.001). Conclusions: Our study suggests a prognostic impact of statin use in patients receiving abiraterone for mCRPC. The mechanism of this interaction warrants elucidation, but may include enhancement of the antitumor activity of abiraterone as well as cardioprotective effects. Patient summary: We assessed the effects of statin use in patients with advanced prostate cancer receiving abiraterone. Patients treated with a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further studies assessing the use of abiraterone plus statins are warranted. Patients with advanced prostate cancer receiving a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further prospective studies are warranted.

KW - Abiraterone

KW - Prostate cancer

KW - Statins

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