Single-nucleotide polymorphism associations with efficacy and toxicity in metastatic castration-resistant prostate cancer treated with cabazitaxel

被引：1

作者：

Herrero Rivera, Daniel ^{[1
,2
]}

Garrigos Vacas, Carmen ^{[3
]}

Marcos Kovandzic, Laura ^{[3
]}

Puente Vazquez, Javier ^{[4
]}

Alonso, Lucia A. ^{[5
]}

Mellado Gonzalez, Begona ^{[6
]}

Calderero Aragon, Veronica ^{[7
]}

Grande, Enrique ^{[8
]}

Luque Caro, Raquel ^{[9
]}

Virizuela Echaburu, Juan A. ^{[10
]}

Rodriguez Moreno, Juan F. ^{[11
]}

Etxebarria, Ainara A. ^{[12
]}

Rodriguez-Antona, Cristina ^{[13
,14
]}

Duran, Ignacio ^{[3
,5
]}

机构：

[1] Hosp Univ Virgen del Rocio, Dept Med Oncol, Seville 41013, Spain

[2] European Univ Madrid, Madrid 28670, Spain

[3] Univ Seville, Invest Mol & Traslac Oncol, Biomed Inst Sevilla, IBiS,Univ Hosp Virgen del Rocio,CSIC, Seville 41013, Spain

[4] Hosp Clin San Carlos, Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Dept Med Oncol, CIBERONC, Madrid 28040, Spain

[5] Hosp Univ Marques de Valdecilla Santander, Dept Med Oncol, Santander 39008, Spain

[6] Hosp Clin Barcelona, Dept Med Oncol, Barcelona 08036, Spain

[7] Hosp Barbastro, Dept Med Oncol, Huesca 22300, Spain

[8] MD Anderson Canc Ctr Espana, Dept Med Oncol, Madrid 28033, Spain

[9] Hosp Univ Virgen de las Nieves, Inst Invest Biosanitaria Ibs, Dept Med Oncol, Granada 18014, Spain

[10] Hosp Univ Virgen Macarena, Dept Med Oncol, Seville 41009, Spain

[11] HM Sanchinarro Clara Campal Comprehens Canc Ctr, Oncol Unit, Madrid 28050, Spain

[12] Hosp Univ Marques de Valdecilla Santander, Dept Pathol, Santander 39008, Spain

[13] Spanish Natl Canc Reaserch Ctr CNIO, Hereditary Endocrine Canc Grp, Madrid 28029, Spain

[14] ISCIII Ctr Biomed Reaserch Rare Dis CIBERER, Madrid 28029, Spain

来源：

PHARMACOGENOMICS | 2022年 / 23卷 / 11期

关键词：

cabazitaxel; metastatic castration-resistant prostate cancer; pharmacodynamics; pharmacokinetics; single nucleotide polymorphism; taxanes; OPEN-LABEL; DOCETAXEL; MITOXANTRONE; PREDNISONE; THERAPY;

D O I：

10.2217/pgs-2022-0023

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background: The aim of this study was to evaluate the impact of certain single-nucleotide polymorphisms (SNPs) in cabazitaxel activity and toxicity in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: 56 SNPs in five genes (CYP3A4, CYP3A5, ABCB1, TUBB1 and CYP2C8) were genotyped in 67 mCRPC patients and their correlation with outcomes analyzed. Results: TUBB1-rs151352 (hazard ratio: 0.52) and CYP2C8-rs1341164 (hazard ratio: 0.53) were associated with better overall survival, and CYP2C8-rs1058932 with biochemical progression (odds ratio: 6.60) in multivariate analysis. ABCB1-rs17327624 correlated with severe toxicity >= grade 3 (odds ratio: 8.56) and CYP2C8-rs11572093 with asthenia (odds ratio: 8.12). Conclusion: Genetic variants in mCRPC patients could explain different outcomes with cabazitaxel. Nonetheless, the small sample size and the high number of SNPs analyzed mean that the results are only hypothesis-generating and require further validation.

引用

页码：627 / 638

页数：12

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