Milano G, Etienne M C
Laboratoire d' Oncopharmacologie, Centre Antoine Lacassagne, Nice, France.
Anticancer Res. 1994 Nov-Dec;14(6A):2295-7.
Fluorouracil (FU) is essentially eliminated in the liver through the rate limiting enzyme dihydropyrimidine dehydrogenase (DPD). DPD is also expressed in various other normal as well as in tumor tissues. DPD activity measured in peripheral blood mononuclear cells (PBMC) is correlated to FU systemic clearance, but this correlation is weak, precluding PBMC-DPD to be considered as a reliable predictor of FU clearance. Nevertheless, patients with suspected or proven PBMC-DPD deficiency exhibit severe FU-related toxicities. Population studies performed so far were unable to detect complete DPD deficient patients, suggesting that complete DPD deficiency is a very rare event; however 3% of patients exhibit a partial DPD deficiency indicative of increased risk for developing FU-related toxicity. Although FU resistance is multifactorial, DPD activity in tumor cells (in vitro and clinical studies) is significantly related to FU sensitivity: the lower the DPD activity, the greater the FU efficacy. Further prospective clinical studies will be required in order to confirm the present observations.
氟尿嘧啶（FU）主要通过限速酶二氢嘧啶脱氢酶（DPD）在肝脏中被清除。DPD也在各种其他正常组织以及肿瘤组织中表达。在外周血单核细胞（PBMC）中测得的DPD活性与FU的全身清除率相关，但这种相关性较弱，这使得PBMC-DPD不能被视为FU清除率的可靠预测指标。然而，疑似或已证实存在PBMC-DPD缺乏的患者会出现严重的FU相关毒性。迄今为止进行的人群研究未能检测到完全DPD缺乏的患者，这表明完全DPD缺乏是一种非常罕见的情况；然而，3%的患者表现出部分DPD缺乏，这表明发生FU相关毒性的风险增加。尽管FU耐药是多因素的，但肿瘤细胞中的DPD活性（体外和临床研究）与FU敏感性显著相关：DPD活性越低，FU疗效越好。需要进一步的前瞻性临床研究来证实目前的观察结果。
