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Pharmacogenomics. 2016 Apr;17(5):463-71. doi: 10.2217/pgs.15.186. Epub 2016 Mar 29.

SNPs associated with activity and toxicity of cabazitaxel in patients with advanced urothelial cell carcinoma.

Author information

1
Hospital Universitario Virgen del Rocio, Seville, Spain.
2
Spanish Oncology Genitourinary Group, Madrid, Spain.
3
Hospital Universitario Gregorio Marañon. Madrid, Spain.
4
Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
5
Instituto Catalan de Oncologia Josep Trueta, Girona, Spain.
6
Complejo Hospitalario de Navarra, Pamplona, Spain.
7
Instituto Catalan de Oncologia, L'Hospitalet, Spain.
8
Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
9
Instituto Valenciano de Oncologia, Valencia, Spain.
10
Hospital de la Santa Creu y Sant Pau, Barcelona, Spain.
11
Instituto Catala de Oncologia, Hospital Universitario Germans Trias y Pujol, Badalona, Spain.
12
Centro Integral Oncologico Clara Campal, Madrid, Spain.
13
Corporacio Sanitaria Parc Tauli, Sabadell, Spain.
14
MD Anderson Madrid, Madrid, Spain.
15
Hospital Universitario Son Espases, Palma de Mallorca, Spain.
16
Hospital Universitario Virgen de la Victoria, Malaga, Spain.
17
Hospital Lucus Augusti, Lugo, Spain.
18
Hospital Universitario Virgen de las Nieves, Granada, Spain.
19
ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.

Abstract

AIM:

We aimed to identify SNPs associated with cabazitaxel toxicity and response within a Phase II clinical trial using this compound in advanced transitional cell carcinoma after progression to a platinum-based regimen.

PATIENTS & METHODS:

Eleven SNPs in CYP3A4, CYP3A5, CYP2C8, ABCB1 and TUBB1 were genotyped in 45 patients.

RESULTS:

CYP3A5 rs776746 A allele was associated with protection against gastrointestinal toxicity (odds ratio: 0.06, 95% CI: 0.007-0.63, p = 0.018) and with reduced progression-free survival (hazard ratio: 5.1, 95% CI: 1.7-15.1, p = 0.0038, multivariable analysis). ABCB1 SNPs were associated with total number of grade 3-4 toxicity events (p-values of 0.009, 0.041 and 0.043, respectively).

CONCLUSION:

Polymorphisms in CYP3A5 and ABCB1 may define a subset of patients with different cabazitaxel toxicity and efficacy and therefore could be used as markers for treatment optimization.

KEYWORDS:

SNPs; biomarkers; cabazitaxel; genitourinary transitional cell carcinoma; pharmacogenetics

PMID:
27020167
DOI:
10.2217/pgs.15.186
[Indexed for MEDLINE]

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