Asunto(s)
Quinasa de Linfoma Anaplásico/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Tromboembolia/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Reordenamiento Génico , Humanos , Incidencia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Portugal/epidemiología , Pronóstico , Proteínas Tirosina Quinasas Receptoras/genética , Estudios Retrospectivos , España/epidemiología , Análisis de Supervivencia , Tromboembolia/genética , Adulto JovenRESUMEN
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.