ERCC1 polymorphisms in patients with advanced bladder cancer treated with platinum-based chemotherapy.

e15066 Background: Platinum-based combination chemotherapy represents the standard treatment for advanced urothelial cancer. Determination of prognosis is based on clinical characteristics: ECOG PS and sites of metastases. ERCC1 is involved in the repair of DNA adducts formed by platinum analogues. Recent data suggest that tissue expression of ERCC1 may have prognostic significance. We studied the prognostic relevance of ERCC1 polymorphisms in the blood from patients with advanced bladder cancer treated with platinum-based chemotherapy. Methods: Patients with inoperable (cT4b, N2, N3) or metastatic bladder cancer were included. Treatment consisted of cisplatin-based chemotherapy (n=65) in the context of a randomized trial of HECOG (HD MVAC vs. HD Cem/Cis) or carboplatin/gemcitabine (n=12) for unfit-for-cisplatin patients. DNA was extracted from blood and was amplified using nested PCR and SNPs C19007T and C8092A were studied. The findings were expressed as C/C (normal), C/T and C/A (heterozygous SNP) and T/T and A/A (homozygous SNP). Results: Seventy patients have been included in this analysis. Median PFS was 11 months (95% CI: 8-14) and median OS 15 months (95% CI: 7-22). SNP C17009T: C/C 18 (26%), C/T 34 (48%), T/T 18 (26%); SNP C8092A: C/C 20 (28%), C/A 44 (63%), A/A 6 (9%). Female patients had higher C19007T T/T and lower C/C expression (60% vs. 20% and 10% vs. 28%, p=0.026). Heterozygous C8092A polymorphism was associated with higher frequency of locoregional relapse (95% vs. 77%, p=0.048) and higher frequency of Hb > 10mg/dL (98% vs. 81%, p=0.046). There was no association of SNPs with objective responses. The presence of distant metastases was associated with significantly lower PFS and OS (13 vs. 8 months, p=0.047 and 20 vs. 12 months, p=0.043). Neither SNP17009 nor SNP8092A was associated with a significant difference in PFS or OS. Conclusions: ERCC1 SNPs are present in the majority of patients with advanced baldder cancer. C8092A SNP is associated with prognostically important clinical characteristics but in this cohort of patients treated with platinum-based chemotherapy did not show any predictive or prognostic significance. No significant financial relationships to disclose.