Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer
Abiraterone acetate (AA) is the first-in-class of drugs belonging to the second-generation of agents inhibiting androgen neosynthesis in advanced prostate cancer. A cumulative experience attests that germinal gene polymorphisms may play a role in the prediction of anticancer agent pharmacodynamics v...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/2/651 |
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| author | Jean-Marc Ferrero Hakim Mahammedi Gwenaelle Gravis Guilhem Roubaud Philippe Beuzeboc Remi Largillier Delphine Borchiellini Claude Linassier Nathalie Ebran Tanguy Pace-Loscos Marie-Christine Etienne-Grimaldi Renaud Schiappa Jocelyn Gal Gérard Milano |
| author_facet | Jean-Marc Ferrero Hakim Mahammedi Gwenaelle Gravis Guilhem Roubaud Philippe Beuzeboc Remi Largillier Delphine Borchiellini Claude Linassier Nathalie Ebran Tanguy Pace-Loscos Marie-Christine Etienne-Grimaldi Renaud Schiappa Jocelyn Gal Gérard Milano |
| author_sort | Jean-Marc Ferrero |
| collection | DOAJ |
| description | Abiraterone acetate (AA) is the first-in-class of drugs belonging to the second-generation of agents inhibiting androgen neosynthesis in advanced prostate cancer. A cumulative experience attests that germinal gene polymorphisms may play a role in the prediction of anticancer agent pharmacodynamics variability. In the present prospective, multicentric study, gene polymorphisms of CYP17A1 (AA direct target) and the androgen transporter genes SLCO2B1 and SLCO1B3 (potential modulators of AA activity) were confronted with AA pharmacodynamics (treatment response and toxicity) in a group of 137 advanced prostate cancer patients treated in the first line by AA. The median follow-up was 56.3 months (95% CI [52.5–61]). From multivariate analysis, rs2486758 C/C (<i>CYP17A1</i>) and PSA (≥10 ng/mL) were associated with a shorter 3-year biological PFS (HR = 4.05, IC95% [1.46–11.22]; <i>p</i> = 0.007 and HR = 2.08, IC95% [1.31–3.30]; <i>p</i> = 0.002, respectively). From a multivariate analysis, the rs743572 (<i>CYP17A1</i>) and performance status were independently associated with significant toxicity (OR = 3.78 (IC95% [1.42–9.75]; <i>p</i> = 0.006 and OR = 4.54; IC95% [1.46–13.61]; <i>p</i> = 0.007, respectively). Host genome characteristics may help to predict AA treatment efficacy and identify patients at risk for toxicity. |
| first_indexed | 2024-03-11T08:17:16Z |
| format | Article |
| id | doaj.art-c04920b18f914032b1945806680881d4 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:17:16Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c04920b18f914032b1945806680881d42023-11-16T22:42:48ZengMDPI AGPharmaceutics1999-49232023-02-0115265110.3390/pharmaceutics15020651Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate CancerJean-Marc Ferrero0Hakim Mahammedi1Gwenaelle Gravis2Guilhem Roubaud3Philippe Beuzeboc4Remi Largillier5Delphine Borchiellini6Claude Linassier7Nathalie Ebran8Tanguy Pace-Loscos9Marie-Christine Etienne-Grimaldi10Renaud Schiappa11Jocelyn Gal12Gérard Milano13Medical Oncology Department, Centre Antoine Lacassagne, University Côte d’Azur, 06189 Nice, FranceMedical Oncology Department, Centre Jean Perrin, 63011 Clermond Ferrand, FranceMedical Oncology Department, Institut Paoli Calmette, 13009 Marseille, FranceDepartment of Medical Oncology, Institut Bergonié, 33076 Bordeaux, FranceMedical Oncology Department, Institut Curie, 75005 Paris, FranceMedical Oncology Department, Centre Azuréen de Cancérologie, 06250 Mougins, FranceMedical Oncology Department, Centre Antoine Lacassagne, University Côte d’Azur, 06189 Nice, FranceMedical Oncology Department, Centre Hospitalier Régional Universitaire, 37044 Tours, FranceOncopharmacology Unit, Centre Antoine Lacassagne, University Côte d’Azur, 06189 Nice, FranceEpidemiology and Biostatistics Department, Centre Antoine Lacassagne, University Côte d’Azur, 06189 Nice, FranceOncopharmacology Unit, Centre Antoine Lacassagne, University Côte d’Azur, 06189 Nice, FranceEpidemiology and Biostatistics Department, Centre Antoine Lacassagne, University Côte d’Azur, 06189 Nice, FranceEpidemiology and Biostatistics Department, Centre Antoine Lacassagne, University Côte d’Azur, 06189 Nice, FranceOncopharmacology Unit, Centre Antoine Lacassagne, University Côte d’Azur, 06189 Nice, FranceAbiraterone acetate (AA) is the first-in-class of drugs belonging to the second-generation of agents inhibiting androgen neosynthesis in advanced prostate cancer. A cumulative experience attests that germinal gene polymorphisms may play a role in the prediction of anticancer agent pharmacodynamics variability. In the present prospective, multicentric study, gene polymorphisms of CYP17A1 (AA direct target) and the androgen transporter genes SLCO2B1 and SLCO1B3 (potential modulators of AA activity) were confronted with AA pharmacodynamics (treatment response and toxicity) in a group of 137 advanced prostate cancer patients treated in the first line by AA. The median follow-up was 56.3 months (95% CI [52.5–61]). From multivariate analysis, rs2486758 C/C (<i>CYP17A1</i>) and PSA (≥10 ng/mL) were associated with a shorter 3-year biological PFS (HR = 4.05, IC95% [1.46–11.22]; <i>p</i> = 0.007 and HR = 2.08, IC95% [1.31–3.30]; <i>p</i> = 0.002, respectively). From a multivariate analysis, the rs743572 (<i>CYP17A1</i>) and performance status were independently associated with significant toxicity (OR = 3.78 (IC95% [1.42–9.75]; <i>p</i> = 0.006 and OR = 4.54; IC95% [1.46–13.61]; <i>p</i> = 0.007, respectively). Host genome characteristics may help to predict AA treatment efficacy and identify patients at risk for toxicity.https://www.mdpi.com/1999-4923/15/2/651prostate cancerabiraterone acetatepharmacodynamicspharmacogenetics |
| spellingShingle | Jean-Marc Ferrero Hakim Mahammedi Gwenaelle Gravis Guilhem Roubaud Philippe Beuzeboc Remi Largillier Delphine Borchiellini Claude Linassier Nathalie Ebran Tanguy Pace-Loscos Marie-Christine Etienne-Grimaldi Renaud Schiappa Jocelyn Gal Gérard Milano Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer Pharmaceutics prostate cancer abiraterone acetate pharmacodynamics pharmacogenetics |
| title | Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer |
| title_full | Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer |
| title_fullStr | Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer |
| title_full_unstemmed | Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer |
| title_short | Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer |
| title_sort | abigene a prospective multicentric study of abiraterone acetate pharmacogenetics in metastatic castration resistant prostate cancer |
| topic | prostate cancer abiraterone acetate pharmacodynamics pharmacogenetics |
| url | https://www.mdpi.com/1999-4923/15/2/651 |
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