Prediction of response in patients (pts) with advanced gastric cancer (AGC) who received paclitaxel-based chemotherapy: Expression of class III beta tubulin (bTubIII) and ABCB1 gene polymorphisms.

Abstract

e14528 Background: Several studies looked for predictive biomarkers for treatment outcome of paclitaxel, but still now no reliable biomarkers are available. To predict clinical outcome in pts with AGC received paclitaxel-based chemotherapy, we evaluated expression of bTulIII and ABCB1 (multidrug resistance) gene polymorphisms. Methods: Sixty Pts with AGC were treated with paclitaxel combined with an infusional 5-fluorouracil and low-dose leucovorin. Expression of bTubIII was evaluated by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tumors from the primary gastric cancer. Tumors were classified as bTulIII “low (< 100)” and “high (≥ 100)” according to IHC score (intensity [0-3]*portion [0-100]). gDNA from peripheral blood mononuclear cells were used to genotype ABCB1 2677G>T/A and 3435C>T polymorphisms. The expression of bTubIII and gene polymorphisms were investigated for their association with tumor response and progression free survival (PFS). Results: The 11 of 60 Pts (18.3%) with high expression of bTubIII showed higher disease control rate (DCR) than those with low expression (90.9 % vs. 51 %, p = 0.019). High bTubIII expression was associated with longer PFS, however there was not statistically significant (5.0 vs. 2.7 months, p = 0.456). The frequencies of ABCB1 2677 genotypes were GG 19.1%, GT + GA 60%, others 20.9% and that of 3435 genotypes were CC 40%, CT 45%, and TT 15%, respectively. ABCB1 2677 GG showed a significantly higher DCR than others (100% vs. 47.4%, p = 0.004). However, ABCB1 2677 genotypes were not associated with PFS and ABCB1 3455 genotypes were not predictive of both DCR and PFS. Conclusions: These results suggested expression of bTubIII and ABCB1 2677 genotypes were predictive markers in pts with AGC received paclitaxel-based chemotherapy. No significant financial relationships to disclose.