Single nucleotide polymorphisms and clinical outcome in biliary tract carcinoma treated with epirubicin, cisplatin and capecitabine.

14558 Background: Biliary tract carcinoma is an uncommon malignancy. The activity of systemic chemotherapy is very low and there is no current therapy considered a gold standard. The poor prognosis of cholangiocarcinoma is a result of its biological aggressiveness and therapy resistant nature. Individual variation in DNA repair conferred by single nucleotide polymorphisms (SNPs) affects the clinical response to therapy and overall survival in several neoplasms. In this investigational pharmacogenetic study we retrospectively evaluated the correlations between the following polymorphisms (XPD Asp312Asn and Lys751Gln, ERCC1 C118T, XRCC1 Arg399Gln, and ABCB1 C3435T) and: drug response, progression free and overall survival.,Between June 2006 and August 2007 33 patients (pts) entered this study: seven pts received epirubicin and cisplatin intravenous and 26 pts received epirubicin and cisplatin intra-arterially; all pts received orally capecitabine. Genomic DNA was extracted from blood samples (5 ml) before drug administration. The ERCC1 C118T, XPD Asp312Asn, XPD Lys751Gln, XRCC1 Arg399Gln, and ABCB1 C3435T polymorphisms were studied with Taqman® probes-based assays.,PR was observed in 6 out of the 33 evaluable pts (18.2%). SD was observed in 17 pts (51.5%) and PD occurred in 10 pts. (30.3%). After a median follow-up of 7.1 months (range 1-44.7), the median PFS was 4.8 months (range 0.7-21.7) and the median OS was 18.9 months. No significant correlations were observed between response, PFS and OS in patients grouped according to all the studied polymorphisms. However, the Log-rank test suggested an association of the XRCC1Arg/Arg variant with reduced OS which did not reach statistical significance. Furthermore, the analysis of survival starting from the date of diagnosis resulted in a significant association of the homozygous variant XRCC1 Arg/Arg with a shorter survival (11.0 vs 45.6 months, p=0.01).,To our knowledge this study is the first pharmacogenetic one in patients affected by biliary tract carcinomas. The results observed in this homogeneous population suggested that the XRCC1 genotype would be useful as prognostic marker in these pts. No significant financial relationships to disclose.