Ruzzo Annamaria, Graziano Francesco, Kawakami Kazuyuki, Watanabe Go, Santini Daniele, Catalano Vincenzo, Bisonni Renato, Canestrari Emanuele, Ficarelli Rita, Menichetti Ettore Tito, Mari Davide, Testa Enrica, Silva Rosarita, Vincenzi Bruno, Giordani Paolo, Cascinu Stefano, Giustini Lucio, Tonini Giuseppe, Magnani Mauro
Medical Oncology Unit, Hospital of Urbino, Urbino, Italy.
J Clin Oncol. 2006 Apr 20;24(12):1883-91. doi: 10.1200/JCO.2005.04.8322.
To investigate whether polymorphisms with putative influence on fluorouracil/cisplatin activity are associated with clinical outcomes of patients with advanced gastric cancer (AGC).
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.
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.
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.
研究对氟尿嘧啶/顺铂活性可能有影响的基因多态性是否与晚期胃癌（AGC）患者的临床结局相关。
对175例接受氟尿嘧啶/顺铂姑息化疗的前瞻性入组AGC患者的外周血样本进行9个基因（TS、MTHFR、XPD、ERCC1、XRCC1、XRCC3、GSTP1、GSTT1、GSTM1）中13种多态性的基因分型。将基因型与反应和生存情况相关联。
总缓解率为41%，中位无进展生存期（PFS）为24周（范围4至50周），中位总生存期（OS）为39周（范围8至72 +周）。化疗耐药和较差的生存情况与TS 5'-UTR 3G基因型（2R/3G、3C/3G、3G/3G）和GSTP1 105 A/A纯合基因型显著相关。61例患者（35%）未表现出任何这些风险基因型（0组），57例患者（32.5%）表现出两种风险基因型中的一种（1组），57例患者（32.5%）表现出两种风险基因型（2组）。0组患者的中位PFS和OS分别为32周（范围8至50周）和49周（范围18至72 +周）。1组和2组患者的PFS（中位分别为26周[范围6至44周]和14周[范围4至38周]）和OS（中位分别为39周[范围10至58周]和28周[范围8至56周]）均显著差于0组患者。这种不良影响在多变量分析中仍然存在。
特定的基因多态性可能影响AGC患者的临床结局。基于治疗前基因分型选择姑息化疗可能是一种值得前瞻性研究的创新策略。
