PURPOSE: To investigate whether polymorphisms with putative influence on fluorouracil/cisplatin activity are associated with clinical outcomes of patients with advanced gastric cancer (AGC). PATIENTS AND METHODS: Peripheral blood samples from 175 prospectively enrolled AGC patients treated with fluorouracil/cisplatin palliative chemotherapy were used for genotyping 13 polymorphisms in nine genes (TS, MTHFR, XPD, ERCC1, XRCC1, XRCC3, GSTPI, GSTTI, GSTMI). Genotypes were correlated to response and survival. RESULTS: The overall response rate was 41%, the median progression-free survival (PFS) was 24 weeks (range, 4 to 50 weeks), and the median overall survival (OS) was 39 weeks (range, 8 to 72+ weeks). Chemoresistance and poor survival were significantly associated with TS 5'-UTR 3G-genotype (2R/3G, 3C/3G, 3G/3G) and GSTP1 105 A/A homozygous genotype. Sixty-one patients (35%) did not show any of these risk genotypes (group 0), 57 patients (32.5%) showed one of the two risk genotypes (group 1), and 57 patients (32.5%) showed both risk genotypes (group 2). Median PFS and OS in group 0 patients were 32 weeks (range, 8 to 50 weeks) and 49 weeks (range, 18 to 72+ weeks), respectively. Group 1 and group 2 patients showed significantly worse PFS (median, 26 weeks [range, 6 to 44 weeks] and 14 weeks [range, 4 to 38 weeks], respectively) and worse OS (median, 39 weeks [range, 10 to 58 weeks] and 28 weeks [range, 8 to 56 weeks]), respectively, than group 0 patients. This adverse effect was retained in multivariate analysis. CONCLUSION: Specific polymorphisms may influence clinical outcomes of AGC patients. Selecting palliative chemotherapy on the basis of pretreatment genotyping may represent an innovative strategy that warrants prospective studies.
PURPOSE: To investigate whether polymorphisms with putative influence on fluorouracil/cisplatin activity are associated with clinical outcomes of patients with advanced gastric cancer (AGC). PATIENTS AND METHODS: Peripheral blood samples from 175 prospectively enrolled AGC patients treated with fluorouracil/cisplatin palliative chemotherapy were used for genotyping 13 polymorphisms in nine genes (TS, MTHFR, XPD, ERCC1, XRCC1, XRCC3, GSTPI, GSTTI, GSTMI). Genotypes were correlated to response and survival. RESULTS: The overall response rate was 41%, the median progression-free survival (PFS) was 24 weeks (range, 4 to 50 weeks), and the median overall survival (OS) was 39 weeks (range, 8 to 72+ weeks). Chemoresistance and poor survival were significantly associated with TS 5'-UTR 3G-genotype (2R/3G, 3C/3G, 3G/3G) and GSTP1 105 A/A homozygous genotype. Sixty-one patients (35%) did not show any of these risk genotypes (group 0), 57 patients (32.5%) showed one of the two risk genotypes (group 1), and 57 patients (32.5%) showed both risk genotypes (group 2). Median PFS and OS in group 0 patients were 32 weeks (range, 8 to 50 weeks) and 49 weeks (range, 18 to 72+ weeks), respectively. Group 1 and group 2 patients showed significantly worse PFS (median, 26 weeks [range, 6 to 44 weeks] and 14 weeks [range, 4 to 38 weeks], respectively) and worse OS (median, 39 weeks [range, 10 to 58 weeks] and 28 weeks [range, 8 to 56 weeks]), respectively, than group 0 patients. This adverse effect was retained in multivariate analysis. CONCLUSION: Specific polymorphisms may influence clinical outcomes of AGC patients. Selecting palliative chemotherapy on the basis of pretreatment genotyping may represent an innovative strategy that warrants prospective studies.
Authors: Jung Mook Kang; Nayoung Kim; Sung-Il Cho; Dong Ho Lee; Young Soo Park; Yu Rim Kim; Ji Hyun Park; Mi Kyoung Lee; Joo Sung Kim; Hyun Chae Jung; In Sung Song Journal: Gut Liver Date: 2008-06-30 Impact factor: 4.519
Authors: G Visani; F Loscocco; A Ruzzo; S Galimberti; F Graziano; M T Voso; E Giacomini; C Finelli; E Ciabatti; E Fabiani; S Barulli; A Volpe; D Magro; P Piccaluga; F Fuligni; M Vignetti; P Fazi; A Piciocchi; E Gabucci; M Rocchi; M Magnani; A Isidori Journal: Pharmacogenomics J Date: 2017-12-05 Impact factor: 3.550