Abstract
e15037 Background: Pre-clinical data has shown synergism between P and platinums. We evaluated combination P plus O in aEGC and correlated the treatment outcomes to single nucleotide polymorphisms (SNP) in genes involved in the metabolism of P. These genes include dihydrofolate reductase (DHFR), folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), phosphoribosylaminoimidazolecarboxamide formyltransferase (ATIC), phosphoribosylglycinamide formyltransferase (GART), reduced folate carrier (SLC19A1), proton-coupled folate transporter (SLC46A1) and thymidylate synthase (TYMS) which activate, inactivate, transport and are targets for P. Methods: Objective Response (OR) following P+O was assessed in a 2-stage trial. Patients (pts) with metastatic/unresectable, therapy-naive EGC were eligible and received biweekly O (85mg/m2) + P (Dose level [D] 1, 120mg/m2; dose level -1 [D-1] 100 mg/m2). SNPs in above genes were evaluated in germline DNA and correlated with outcomes. Results: 35 pts, median age 6...
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