Gemcitabine pathway genotype analysis to predict toxicity in phase II gemcitabine monotherapy in heavily pre-treated metastatic breast cancer

Abstract

2066 Background: We evaluated the efficacy and tolerability of gemcitabine monotherapy in heavily pretreated breast cancer patients, and the polymorphism of gemcitabine-related genes to elucidate the association with toxicity. We detected the polymorphism of deoxycytidine kinase (dCK), deoxycytidine deaminase (dCDA), and ribonucleotide reductase (RNR). Methods: A weekly infusion of gemcitabine at 850mg/m2 for 3 of every 4 weeks was introduced in patients who had failed previous doxorubicin and taxane. Treatment was delayed until leukopenia was recovered with G-CSF support without dose modification. The known polymorphism site of 3 genes were evaluated by CEQ™ 8000 Genetic Analysis System (Beckman): dCK(GG->GT), dCDA(AA->AG), RNR(CC-> CT, TT->TC) with genomic DNA of peripheral lymphocytes. Results: Of 51 enrolled patients, 47 were evaluable. Total 208 cycles were administered and the relative dose intensity was 89%. The response rate was 20%. Median response duration and overall survival were 8 and 12 mont...