VEGF-A polymorphisms predict progression-free survival among advanced castration-resistant prostate cancer patients treated with metronomic cyclophosphamide.
Br J Cancer
; 109(4): 957-64, 2013 Aug 20.
Article
en En
| MEDLINE
| ID: mdl-23860526
ABSTRACT
BACKGROUND:
No data are available on the pharmacogenetics of metronomic chemotherapy in prostate cancer. The aim of this study was to evaluate the association between VEGF-A sequence variants and prostate-specific antigen (PSA) progression, progression-free survival (PFS) and overall survival (OS), in advanced castration-resistant prostate cancer patients treated with metronomic cyclophosphamide (CTX), celecoxib and dexamethasone.METHODS:
Forty-three patients were enrolled, and genomic DNA was extracted. VEGF-A gene SNPs (-2578A/C, -634C/G, +936C/T) were analysed using TaqMan PCR assays. Hardy-Weinberg equilibrium was tested for each SNP, and genetic effects were evaluated by Fisher's exact test. PFS and OS were analysed with GraphPad Prism software, using the product limit method of Kaplan and Meier, and comparing survival curves using both the log-rank test and the Gehan-Wilcoxon test. We used Bonferroni correction to account for multiple testing, and a two-tailed P-value of <0.017 was considered statistically significant.RESULTS:
Overall, 20 patients (46%) experienced a reduction in PSA levels from baseline and, among them, 14 (32%) showed a confirmed PSA ≥50% decrease. In non-responders, the -2578CC genotype was more frequent (18.60% vs 2.33% in responders; P=0.0212) whereas the -634CC genotype frequency was 22.73% vs 0% in responders (P=0.0485). With regard to PFS, patients harbouring the -634CC genotype had a median PFS of 2.2 months whereas patients with the genotype -634CG/GG had a median PFS of 6.25 months (P=0.0042).CONCLUSION:
The -634CC genotype is significantly associated with a shorter PFS in patients treated with a metronomic CTX schedule.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Adenocarcinoma
/
Antineoplásicos Alquilantes
/
Inhibidores de la Angiogénesis
/
Ciclofosfamida
/
Factor A de Crecimiento Endotelial Vascular
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Aged
/
Aged80
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Br J Cancer
Año:
2013
Tipo del documento:
Article
País de afiliación:
Italia