title: Incidence and relative risk of adverse events of special interest in patients with castration resistant prostate cancer treated with CYP-17 inhibitors: A meta-analysis of published trials.
abstract: Abiraterone acetate and orteronel are two CYP-17 inhibitors that have been studied in prostate cancer. They have shown relevant toxicities, including fluid retention/oedema, hypokalaemia, hypertension, liver function test abnormalities and cardiac events. The goal of this study was to determine the risk of special adverse events related to CYP- 17 inhibitor in patients with metastatic castration-resistant prostate cancer (CRCP). Summary data from four randomized phase III trials comparing CYP-17 inhibitors and prednisone versus placebo and prednisone in metastatic CRCP patients were meta-analysed. Pooled risk ratios (RRs) for the risk of all-grade and grade 3-4 adverse events of special interest were calculated. Data from 4916 patients (2849 in the AA experimental arm; 2067 in the control arm) were analysed. The incidence of grade 3-4 adverse events was never more than 10% of the patients. However, compared with placebo, the CYP-17 inhibitor significantly increased the all-grade events of hypertension (RR=1.53; 95% CI=1.3-1.8; p<0.00001), hypokalaemia (RR=1.56; 95% CI=1.29-1.89; p<0.00001), cardiac disorders (RR=1.47; 95% CI=1.27-1.7; p<0.00001) liver function test abnormalities (RR=1.93; 95% CI=1.15-3.24; p=0.01) grade≥3 adverse events, hypokalaemia (RR=4.23; 95% CI=1.28-13.99; p=0.02) and cardiac disorders (RR=1.55; 95% CI=1.18-2.05; p=0.002). A lot of adverse events such as hypertension, hypokalaemia, cardiac disorders and liver function test abnormalities are increased during CYP-17 inhibitor based therapy. Strict monitoring of these side effects should be considered during CYP- 17 inhibitor therapy in prostate cancer patients.
authors.affiliation: Section of pharmacology and University Center DIFF-Drug Innovation Forward Future, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25124 Brescia, Italy; Unit of molecular therapy and pharmacogenomic, AO Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy. Electronic address: giandomenicoroviello@gmail.com.
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Roviello
authors.affiliation: Section of pharmacology and University Center DIFF-Drug Innovation Forward Future, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25124 Brescia, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sigala
authors.affiliation: Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University Hospital, Via Roma 55, 56126 Pisa, Italy.
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.affiliation: Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University Hospital, Via Roma 55, 56126 Pisa, Italy.
authors.forename: Marzia Del
authors.initials: MD
authors.lastname: Re
authors.affiliation: Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129 Trieste, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bonetta
authors.affiliation: Unit of molecular therapy and pharmacogenomic, AO Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Cappelletti
authors.affiliation: Unit of molecular therapy and pharmacogenomic, AO Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zanotti
authors.affiliation: Unit of molecular therapy and pharmacogenomic, AO Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bottini
authors.affiliation: Unit of molecular therapy and pharmacogenomic, AO Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100 Cremona, Italy; Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129 Trieste, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Generali
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D013254:Steroid 17-alpha-Hydroxylase
keywords: Abiraterone acetate; Mineralcorticoid events; Orteronel; Prostate cancer; Safety