Association of thymidylate synthase (TS) expression with response to S-1 plus carboplatin (CBDCA) in non-small cell lung cancer (NSCLC) patients (pts)., w( Q4 A: z" T% z
Background: S-1, a novel oral fluoropyrimidine derivative, is active against NSCLC. Phase II studies of S-1 plus platinum compounds have shown activity for first-line treatment of advanced NSCLC. It is important to design an optimal therapeutic strategy according to tumor biology to improve the treatment of NSCLC. In the present study, we evaluated the correlations between immunohistochemical expression of TS, orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine dehydrogenase (DPD), and response to S-1 plus CBDCA in advanced NSCLC pts. Methods: Chemotherapy-naïve pts with advanced stage (IIIB/ IV) NSCLC, ECOG PS of 0-1, adequate organ functions and archival tumor tissue were assigned to receive either CBDCA AUC 5 mg/mL/min on day 1 plus oral S-1 80 mg/m2/day (40 mg/m2 b.i.d.) on days 1 to 14 (22 pts) or CBDCA AUC 6 mg/mL/min plus paclitaxel (PTX) (200 mg/m2) on day 1 every 21 days (26 pts). Association between TS, OPRT and DPD protein expression levels in tumors and response to chemotherapy was evaluated. Results: There was no statistical difference in TS, OPRT and DPD expression level between S-1 plus CBDCA and PTX plus CBDCA. In the S-1 plus CBDCA groups, TS expression of responding tumors was significantly lower than that of nonresponding ones (p = 0.006), whereas no significant difference was observed in the PTX plus CBDCA groups. Furthermore, patients with low TS expression survived longer than those with high TS expression in patients receiving combination therapy with S-1 and CBDCA, but not in those treated with PTX plus CBDCA. Conclusions: Our results suggest that tumor TS expression levels is predictive markers for response to S-1 plus CBDCA chemotherapy in advanced NSCLC pts. ( g, V$ p/ X/ {) s
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