Pharmacogenetic Profiling and Clinical Outcome of Patients With Advanced Gastric Cancer Treated With Palliative Chemotherapy

• DOI: 10.1200/jco.2005.04.8322
• Publication Date: 2006-04-18T22:54:49Z
• Authors: Annamaria Ruzzo; Francesco Graziano; Kazuyuki Kawakami; Go Watanabe; Daniele Santini; Vincenzo Catalano; Renato Bisonni; Emanuele Canestrari; Rita Ficarelli; Ettore Tito Menic...; Davide Mari; Enrica Testa; Rosarita Silva; Bruno Vincenzi; Paolo Giordani; Stefano Cascinu; Lucio Giustini; Giuseppe Tonini; Mauro Magnani
• Keywords: Palliative chemotherapy

To investigate whether polymorphisms with putative influence on fluorouracil/cisplatin activity are associated clinical outcomes of patients advanced gastric cancer (AGC).Peripheral blood samples from 175 prospectively enrolled AGC treated palliative chemotherapy were used for genotyping 13 in nine genes (TS, MTHFR, XPD, ERCC1, XRCC1, XRCC3, GSTPI, GSTTI, GSTMI). Genotypes correlated to response and survival.The overall rate was 41%, the median progression-free survival (PFS) 24 weeks (range, 4 50 weeks), (OS) 39 8 72+ weeks). Chemoresistance poor significantly TS 5'-UTR 3G-genotype (2R/3G, 3C/3G, 3G/3G) GSTP1 105 A/A homozygous genotype. Sixty-one (35%) did not show any these risk genotypes (group 0), 57 (32.5%) showed one two 1), both 2). Median PFS OS group 0 32 weeks) 49 18 respectively. Group 1 2 worse (median, 26 [range, 6 44 weeks] 14 38 weeks], respectively) 10 58 28 56 weeks]), respectively, than patients. This adverse effect retained multivariate analysis.Specific may Selecting basis pretreatment represent an innovative strategy that warrants prospective studies.