title: SNPs associated with activity and toxicity of cabazitaxel in patients with advanced urothelial cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hospital Universitario Virgen del Rocio, Seville, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Duran
authors.affiliation: Spanish Oncology Genitourinary Group, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Hagen
authors.affiliation: Hospital Universitario Gregorio Marañon. Madrid, Spain.
authors.forename: José Ángel
authors.initials: JÁ
authors.lastname: Arranz
authors.affiliation: Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Apellaniz-Ruiz
authors.affiliation: Hospital Universitario Virgen del Rocio, Seville, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Pérez-Valderrama
authors.affiliation: Instituto Catalan de Oncologia Josep Trueta, Girona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Sala
authors.affiliation: Complejo Hospitalario de Navarra, Pamplona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Lainez
authors.affiliation: Instituto Catalan de Oncologia, L'Hospitalet, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: García-Del Muro
authors.affiliation: Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Noguerón
authors.affiliation: Instituto Valenciano de Oncologia, Valencia, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Climent
authors.affiliation: Hospital de la Santa Creu y Sant Pau, Barcelona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Maroto
authors.affiliation: Instituto Catala de Oncologia, Hospital Universitario Germans Trias y Pujol, Badalona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Font
authors.affiliation: Centro Integral Oncologico Clara Campal, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Donas
authors.affiliation: Corporacio Sanitaria Parc Tauli, Sabadell, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Gallardo
authors.affiliation: MD Anderson Madrid, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: López-Criado
authors.affiliation: Hospital Universitario Son Espases, Palma de Mallorca, Spain.
authors.forename: Aránzazu
authors.initials: A
authors.lastname: González Del Alba
authors.affiliation: Hospital Universitario Virgen de la Victoria, Malaga, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Sáez
authors.affiliation: Hospital Lucus Augusti, Lugo, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Vázquez
authors.affiliation: Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Luque
authors.affiliation: Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.|ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez-Antona
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D065727:Cytochrome P-450 CYP2C8 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D014404:Tubulin / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019459:Urothelium / Q000473:pathology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; C578986:TUBB1 protein, human; D043823:Taxoids; D014404:Tubulin; C552428:cabazitaxel; D065727:Cytochrome P-450 CYP2C8; D051544:Cytochrome P-450 CYP3A
keywords: SNPs; biomarkers; cabazitaxel; genitourinary transitional cell carcinoma; pharmacogenetics