原发性肿瘤中胸苷酸合成酶低表达预示着接受替加氟辅助治疗的胃癌切除患者临床预后良好。
Low thymidylate synthase expression in the primary tumor predicts favorable clinical outcome in resected gastric cancer patients treated with adjuvant tegafur.
作者信息
Grau Juan J, Domingo-Domenech Josep, Morente Vanesa, Pera Manuel, Garcia-Valdecasas Juan C, Fuster Josep, Bombí Antoni, Mellado Begoña, Albanell Joan, Gascón Pere
机构信息
Oncology Department, Hospital Clinic, Institute of Hemato-Oncology, University of Barcelona, Barcelona, Spain.
出版信息
Oncology. 2004;66(3):226-33. doi: 10.1159/000077999.
OBJECTIVE
To assess the thymidylate synthase protein (TS) in tumor cells of resected gastric cancer patients treated with adjuvant tegafur (TG), we reviewed the outcome of 94 randomized patients treated either with adjuvant TG plus mitomycin C (MMC) or MMC alone.
METHODS
TS was determined in 76 out of 94 patients, previously randomized to receive adjuvant TG, 500 mg/m(2)/day p.o. for 6 months plus four courses of MMC, 10- 20 mg/m(2) i.v. every 6 weeks or MMC alone. An immunohistochemical assessment with the monoclonal antibody TS-106 was performed.
RESULTS
Low TS was observed in 38 patients (20 treated with TG-MMC and 18 with MMC) and high TS in the other 38 patients (21 treated with TG-MMC and 17 with MMC). After 10 years' median follow-up time, 61% of adjuvant TG-MMC patients and 43% of MMC patients were alive and disease-free. Disease-free survival and overall survival were significantly better for patients treated with TG-MMC compared to MMC adjuvant (p = 0.0277 and p = 0.05), and low-TS compared to high-TS patients (p = 0.0184 and p = 0.0198). In 38 low-TS patients we observed an 83% chance to be disease-free in TG-MMC-treated patients and 55% in MMC-treated patients (p = 0.04).
CONCLUSIONS
A low TS level determines a subset of patients that may benefit from adjuvant oral TG when added to MMC showing a 5-year cure rate of more than 80%.
目的
为评估接受替加氟（TG）辅助治疗的胃癌切除患者肿瘤细胞中的胸苷酸合成酶蛋白（TS），我们回顾了94例随机分组患者的治疗结果，这些患者分别接受了TG联合丝裂霉素C（MMC）辅助治疗或单纯MMC辅助治疗。
方法
94例患者中76例接受了TS检测，这些患者先前被随机分组，接受TG辅助治疗，口服剂量为500 mg/m²/天，持续6个月，加用四个疗程的MMC，静脉注射剂量为10 - 20 mg/m²，每6周一次，或单纯接受MMC治疗。采用单克隆抗体TS - 106进行免疫组化评估。
结果
38例患者TS水平较低（20例接受TG - MMC治疗，18例接受MMC治疗），另外38例患者TS水平较高（21例接受TG - MMC治疗，17例接受MMC治疗）。经过10年的中位随访时间，接受TG - MMC辅助治疗的患者中有61%存活且无疾病复发，接受MMC辅助治疗的患者中有43%存活且无疾病复发。与接受MMC辅助治疗的患者相比，接受TG - MMC治疗的患者无病生存期和总生存期显著更好（p = 0.0277和p = 0.05），与TS水平较高的患者相比，TS水平较低的患者无病生存期和总生存期显著更好（p = 0.0184和p = 0.0198）。在38例TS水平较低的患者中，我们观察到接受TG - MMC治疗的患者无病生存率为83%，接受MMC治疗的患者无病生存率为55%（p = 0.04）。
结论
低TS水平决定了一部分患者，当在MMC基础上加用口服TG辅助治疗时，这些患者可能受益，5年治愈率超过80%。
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