Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), ERCC1, & thymidine phosphorylase gene expression in primary & metastatic (met) colorectal cancer (CRC) tissue in patients (pts) treated on a phase I trial of oxaliplatin (OX) & capecitabine (Xel).

3549 Background: Overexpression of TS/DPD & ERCC1 in tumor tissue have been associated with insensitivity to 5-FU and OX therapy, respectively, while high TP levels predict for increased sensitivity to Xel.,When feasible, biopsies of met tumor were taken in pts before OX (130 mg/m d1)/Xel (1200-3000 mg/m d1-5,8-12) q 3wk. Microdissected met & archival primary tumors were analyzed for gene expression (vs b-actin) of these 4 targets by real-time QRT-PCR. Survival (Surv) & time to treatment failure (TTF) were analyzed by log-rank. Gene expression v outcome was assessed using median (med), 25 & 75 percentiles for each target.,90 pts participated. The med # prior chemotherapies was 2; 96% had prior 5-FU; 78% had prior irinotecan. Med mRNA levels were higher in met v primary tumor (table); rank sum analysis of paired samples showed (med): TS, 4.2 vs 2.2, p<0.001; DPD, 1.7 vs 0.4, p=0.005; ERCC1, 2.3 vs 1.1, p=0.002; TP, 6.3 vs 3.9 p=0.018. Pts whose tumor had ERCC1 >75 % had shorter TTF (med 162 d vs 85 d, p=0.026); pts with TP >75 % tended to have longer TTF (med 194 d vs 146 d, p=0.072). Individual mRNA levels in met tumor did not correlate with Surv, but pts whose tumors had both TS & ERCC1 < med had longer Surv (med 502 vs 296 days, p=0.038).,In this study, target gene expression in primary tumor did not reflect levels in met tissue. In pre-treated CRC pts, mRNA levels of TP & ERCC1 in met tumor had some predictive value for TTF with OX/Xel therapy. Low levels of TS & ERCC1 predicted for improved Surv. [Figure: see text] [Table: see text].