RESUMO
Taxanes are used in the treatment of several solid tumours. Adverse events (AEs) might be influenced by single nucleotide polymorphisms (SNPs) in genes encoding proteins responsible for pharmacokinetic and pharmacodynamic. In this prospective, monocentric, observational study we explored the effect of SNPs in the main genes involved in taxanes metabolism and transport, on toxicity and efficacy in 125 patients (pts) treated with paclitaxel, nab-paclitaxel, or docetaxel for neoplasms. There was no statistically significant association between the investigated SNPs and AEs. The heterozygous genotype of CYP3A4*22 showed a trend of association with skin reactions in pts treated with paclitaxel and nab-paclitaxel (RR = 6.92; 95% CI 0.47, 99.8; p = 0.0766). CYP2C8*3/*4 variant carriers showed a trend of association with overall AEs in pts treated with paclitaxel and nab-paclitaxel (RR = 1.28; 95% CI 0.96, 1.67; p = 0.0898). No statistically significant relationship with treatment efficacy was found. ABCB1 3435TT showed a trend of association with a higher treatment response (RR = 0.22; 95% CI 0.03, 1.51; p = 0.0876). Despite the population was heterogeneous, CYP3A4*22 and CYP2C8 SNPs may influence paclitaxel and nab-paclitaxel toxicity and ABCB1 c.3435 may affect taxanes effectiveness, even if any statistically significant was found.
Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/uso terapêutico , Citocromo P-450 CYP3A/genética , Docetaxel/uso terapêutico , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Farmacogenética/métodos , Estudos ProspectivosRESUMO
Clear cell renal carcinoma (ccRCC) can occur in young people and could be associated with an aggressive behavior. While for the first-line treatment in metastatic disease, there is an agreement to rely on an immunotherapy (IO)-based combination regimen, no standard second-line regimens exist. Generally, tyrosine kinase inhibitors (TKIs) are employed, even in sequence, although no trials have demonstrated yet the best succession. Herein, we present the case of a 39-year-old male, with a very aggressive ccRCC with somatic VHL mutation and distant metastases at diagnosis. He was treated with four different lines of therapies, including TKIs, with progressive multiple tumor deposits. Lenvatinib alone as the fifth line was able to induce a remarkable and prolonged tumor shrinkage with manageable toxicities.