Favorable genetic polymorphisms predictive of clinical outcome of chemoradiotherapy for stage II/III esophageal squamous cell carcinoma in Japanese
Favorable genetic polymorphisms predictive of clinical outcome of chemoradiotherapy for stage II/III esophageal squamous cell carcinoma in Japanese
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DOI：
10.1097/01.coc.0000256059.88247.25
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发表时间：
2007-06-01
影响因子：
2.6
通讯作者：
Sakaeda, Toshiyuki
中科院分区：
文献类型：
--
作者：
Okuno, Tatsuya;Tamura, Takao;Sakaeda, Toshiyuki
目的：探讨以5-氟尿嘧啶(5-Fu)/顺铂(CDDP)为基础的放化疗(CRT)对日本局部晚期食管鳞癌(ESCC)患者临床疗效的影响。材料与方法：选择I/II/III/IVA期食管鳞癌患者31例(I/II/III/IVA=7/7/14/3)。1个疗程包括5-FU(400 mg/m(2)/24 h，第1~5天、8~12天)、顺铂(40 mg/m(2)/3h，第1、8天)和放疗(2Gyd，第1~5天、8~12天、15~19天)，第2个疗程间隔2周后连续重复。用高效液相色谱法测定了8次5-FU血药浓度。结果：CR率与临床分期有关(P=0.001)，但对2年生存率影响不大(P=0.061)。对于II/III期患者，5‘-TSER的3R/3R、3’-TSUTR6个碱基和GSTPI-Ile105Val有2或3个或3个基因多态性可显著延长患者的生存期(P=0.020)，尽管两组患者的5-FU血药浓度和临床病理特征无明显差异。结论：该预后指标可用于预测以5-FU/CDDP为基础的化疗方案对II/III期食管癌患者的临床疗效。
Objectives: This study was performed to find the genetic factors predictive of clinical outcome to a 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT) in Japanese patients with locally advanced esophageal squamous cell carcinoma (ESCC).Materials and Methods: Thirty-one patients with stage I-IVa ESCC (I/II/III/IVa = 7/7/14/3) were enrolled in this study. One course of treatment consisted of protracted venous infusions (PVIs) of 5-FU (400 mg/m(2)/24 hours for days 1-5 and 8-12), CDDP (40 mg/m(2) /3 hours on days 1 and 8) and radiation (2 Gy/d on days 1-5, 8-12, and 15-19), and a 2nd course was successively repeated after a 2-week interval. A total of 8 measurements of the plasma concentration of 5-FU were made using high performance liquid chromatography. Genetic polymorphisms examined herein included those in the genes coding thymidylate synthase (TS), glutathione S-transferase PI (GSTPI), multidrug resistant transporter MDR1/P-glycoprotein, and intercellular adhesion molecule-1, and in a circadian rhythm-relating gene, CLOCK.Results: The CR rate depended on stage (P = 0.001), but the analysis was not sufficiently powered to reach a level of statistical significance for the 2-year survival rate (P = 0.061). For stage II/III patients, to have 2 or 3 polymorphisms of 3R/3R of 5'-TSER, a 6 bp of 3'-TSUTR, and GSTPI-Ile105Val resulted in an extensively longer survival (P = 0.020), although no difference was found between 2 groups, with respect to the plasma concentrations of 5-FU and clinicopathologic characteristics.Conclusions: The prognostic index may allow predictions of the clinical outcome of a 5-FU/CDDP-based CRT in stage II/III ESCC patients.