KDR genetic predictor of toxicities induced by sorafenib and regorafenib.
Pharmacogenomics J
; 22(5-6): 251-257, 2022 12.
Article
en En
| MEDLINE
| ID: mdl-35484400
ABSTRACT
No biomarkers are available to predict toxicities induced by VEGFR TKIs. This study aimed to identify markers of toxicities induced by these drugs using a discovery-validation approach. The discovery set included 140 sorafenib-treated cancer patients (TARGET study) genotyped for SNPs in 56 genes. The most significant SNPs associated with grade ≥2 hypertension, diarrhea, dermatologic toxicities, and composite toxicity (any one of the toxicities) were tested for association with grade ≥2 toxicity in a validation set of 201 sorafenib-treated patients (Alliance/CALGB 80802). The validated SNP was tested for association with grade ≥2 toxicity in 107 (LCCC 1029) and 82 (Italian cohort) regorafenib-treated patients. SNP-toxicity associations were evaluated using logistic regression, and a meta-analysis between the studies was performed by inverse variance. Variant rs4864950 in KDR increased the risk of grade ≥2 composite toxicity in TARGET, Alliance/CALGB 80802, and the Italian cohort (meta-analysis p = 6.79 × 10-4, OR = 2.01, 95% CI 1.34-3.01). We identified a predictor of toxicities induced by VEGFR TKIs. CLINICALTRIALS.GOV IDENTIFIER NCT00073307 (TARGET), NCT01015833 (Alliance/CALGB 80802), and NCT01298570 (LCCC 1029).
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Compuestos de Fenilurea
/
Neoplasias
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
/
Systematic_reviews
Límite:
Humans
Idioma:
En
Revista:
Pharmacogenomics J
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos