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Clin Genitourin Cancer. 2013 Sep;11(3):229-37. doi: 10.1016/j.clgc.2013.04.007. Epub 2013 May 17.

Phase II study of satraplatin and prednisone in patients with metastatic castration-resistant prostate cancer: a pharmacogenetic assessment of outcome and toxicity.

Author information

1
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. figgw@helix.nih.gov.

Abstract

BACKGROUND:

We assessed the effect of excision repair cross-complementing group 1 (ERCC1) and x-ray cross-complementing group 1 (XRCC1) gene polymorphisms on treatment outcomes with satraplatin and prednisone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel-based therapy.

PATIENTS AND METHODS:

Twenty-four patients were enrolled in this single arm study. The primary objective was to determine if the presence of ERCC1 Asn118Asn (N118N, 500C>T, rs11615) and XRCC1 Arg399Gln (R399Q, 1301G>A, rs25487) genetic variants might be associated with an impact on progression-free survival (PFS); secondary objectives included overall response, survival, and toxicity.

RESULTS:

After population stratification by race, white patients carrying heterozygous or variant genotypes at the ERCC1 C>T locus had a >3-fold longer median PFS (5.8 vs. 1.8 months; 2P = .18, adjusted) and 5-fold longer median overall survival (OS) (15.7 vs. 3.2 months; 2P = .010, adjusted) than did patients carrying only wild-type alleles. For the XRCC1 G>A variant, without regard to race, patients carrying the wild-type GG alleles had a longer PFS (9.3 months) than those carrying GA or AA alleles (2.7 months; 2P = .02). Similarly, those carrying GG alleles did not reach median OS, whereas those carrying GA or AA alleles had a median OS of 9.6 months (2P = .12, adjusted). Multivariable analysis by using Cox proportional hazards modeling demonstrated that only XRCC1 was associated with PFS.

CONCLUSIONS:

To our knowledge, this is the first prospective study to date in patients with metastatic castration-resistant prostate cancer that describes predictive germline polymorphisms of ERCC1 and XRCC1 for assessing the clinical activity of satraplatin.

KEYWORDS:

ERCC1; Genotyping; Prostate cancer; Satraplatin; XRCC1

PMID:
23684781
PMCID:
PMC3758779
DOI:
10.1016/j.clgc.2013.04.007
[Indexed for MEDLINE]
Free PMC Article
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