The Relationship Of Polymorphisms Of Angiogenesis Associated Genes With Efifcacy For Advanced Gastric Cancer Patients With First-line Chemotherapy

【Objective】 The aim of the study was to evaluate the clinical efficacy andtoxicity of docetaxel based or oxaliplatin based regimens as first linechemotherapy in patients with advanced gastric carcinoma and to explore thepotential predictors of therapeutic effect and prognosis through detecting thesingle nucleotide polymorphisms of angiogenesis associated genes. MethodPatients in Chinese PLA general hospital from January2008to June2011withunresectable gastric carcinoma who underwent docetaxel based(DCF/DF/DX) oroxaliplatin based(FOLFOX/SOX/XELOX) regimen as first line chemotherapywere retrospectively reviewed. Clinical efficacy and toxicity between twochemotherapy groups were compared. Fiveteen gene polymorphisms weredetermined by real time PCR using genomic DNA extracted from blood samplesof128patients among above193patients. To evaluate the correlation between15single nucleotide polymorphism (SNPs) of angiogenesis associated genes,clinicopathological characteristics and survival. Result Of one hundred andninety-three assessable patients, the median follow-up was28months. UntillMarch30th2012, there were174(92.7%) cases dead.1. The RR of TXT basedregimen and OXA based regimen was28.8%and27.9%respectively (P>0.05),DCR was78%and73.8%respectively (P>0.05). Neither mPFS(4.75VS3.89months) nor mOS(10.24VS8.86) showed significant difference(P>0.05).Theincidence rate of3-4grade leukocytopenia and alopecia of the TXT group washigher than the OXA group, the incidence rate of gastrointestinal side effects ofthe former was lower than the latter’s (P＜0.05).2. Kaplan-Meier analysis ofthe association between one hundred and twenty-eight patient’s15SNPs andtheir PFS and OS, Endostatin+4349GA genotype, eNOS-786CC genotype and VEGFR21416TT genotype showed a significantly shorter PFS and OS(P＜0.05), the VEGF-2578CA and VEGF-1498CT genotype only associated withpoorer OS.3. Multivariate survival analysis demonstrated Endostatin+4349G>A genotype was a significant independent prognostic factor for PFS in128AGC patients. Endostatin+4349G>A genotype and eNOS-786T>C genotypewere significant independent prognostic factors for OS (P＜0.05).Conclusions:1. Docetaxel based and oxaliplatin based regimens both are effective first-linechemotherapy treatments with tolerable toxicity, there was no significantefficacy difference between them.2. Number of organs involved was asignificant independent prognostic factor for PFS while number of organsinvolved, histological grade and KPS score were significant independentprognostic factors for OS.3. Endostatin+4349GA genotype, eNOS-786CCgenotype and VEGFR21416TT genotype showed a significantly shorter PFSand OS simultaneously, multivariate survival analysis revealed that Endostatin+4349G>A variants was a significant independent prognostic factor for bothPFS and OS, tend to become potential predictive biomarkers for advancedgastric carcinoma patients who received the first line chemotherapy. Thesefindings are looking for large-scale clinical trial to further confirm.