Giuseppe Di Lorenzo1, Guru Sonpavde2, Gregory Pond3, Giuseppe Lucarelli4, Sabrina Rossetti5, Gaetano Facchini5, Sarah Scagliarini6, Giacomo Cartenì6, Piera Federico7, Bruno Daniele8, Franco Morelli9, Teresa Bellelli10, Matteo Ferro11, Sabino De Placido11, Carlo Buonerba12. 1. Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy. Electronic address: dilorengiuseppe@gmail.com. 2. Department of Medicine, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL, USA. 3. McMaster University, Hamilton, Ontario, Canada. 4. Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy. 5. Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy. 6. Unità Operativa Sperimentazioni Cliniche Oncologia, Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli", Naples, Italy. 7. Medical Oncology Department, G. Rummo Hospital, Benevento, Italy. 8. Department of Medical Oncology, Casa Sollievo della Sofferenza Hospital, Medical Oncology, San Giovanni Rotondo, Italy. 9. Medical Oncology, Hospital San Luca, Vallo della Lucania, Salerno, Italy. 10. Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Italy. 11. Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy. 12. Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Italy.
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.
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.
Authors: Jacob A Gordon; Jake W Noble; Ankur Midha; Fatemeh Derakhshan; Gang Wang; Hans H Adomat; Emma S Tomlinson Guns; Yen-Yi Lin; Shancheng Ren; Collin C Collins; Peter S Nelson; Colm Morrissey; Kishor M Wasan; Michael E Cox Journal: Cancer Res Date: 2019-05-07 Impact factor: 12.701
Authors: Joseph Longo; Stephen J Freedland; Linda Z Penn; Robert J Hamilton Journal: Prostate Cancer Prostatic Dis Date: 2022-06-29 Impact factor: 5.554
Authors: Jacob A Gordon; Carlo Buonerba; Gregory Pond; Daniel Crona; Silke Gillessen; Giuseppe Lucarelli; Sabrina Rossetti; Tanya Dorff; Salvatore Artale; Jennifer A Locke; Davide Bosso; Matthew Ivan Milowsky; Mira Sofie Witek; Michele Battaglia; Sandro Pignata; Cyrus Cherhroudi; Michael E Cox; Pietro De Placido; Dario Ribera; Aurelius Omlin; Gaetano Buonocore; Kim Chi; Christian Kollmannsberger; Daniel Khalaf; Gaetano Facchini; Guru Sonpavde; Sabino De Placido; Bernhard J Eigl; Giuseppe Di Lorenzo Journal: Oncotarget Date: 2018-04-13