POPULATION STUDY OF DIHYDROPYRIMIDINE DEHYDROGENASE IN CANCER-PATIENTS
POPULATION STUDY OF DIHYDROPYRIMIDINE DEHYDROGENASE IN CANCER-PATIENTS
复制标题
DOI：
10.1200/jco.1994.12.11.2248
复制
发表时间：
1994-11-01
影响因子：
45.3
通讯作者：
MILANO, G
中科院分区：
文献类型：
--
作者：
ETIENNE, MC;LAGRANGE, JL;MILANO, G
目的：我们进行了一项前瞻性研究，在一个大的癌症患者，试图评估的发病率完全或部分二氢嘧啶脱氢酶（DPD）缺乏发现在外周血单核细胞（PMNC）hepatocyte and Methods：一百八十五个连续的癌症患者。人群包括152名男性（平均年龄62.1岁;范围35 - 90岁）和33名女性（平均年龄59.2岁;范围36 - 77岁）。68名头颈部患者接受氟尿嘧啶连续输注5天（FU;起始剂量为1 g/m2/d，根据药代动力学调整剂量），在FU给药前2 - 3天测量DPD活性（分析了194个周期）。结果：整个人群的DPD活性呈单峰分布，总体上符合高斯分布。DPD活性的平均值和中位值分别为0.222和0.211 nmol/min/mg蛋白（范围：0.065 - 0.559）。多因素方差分析显示，肝功能（生物学评价）和年龄并不影响DPD活性，但女性的DPD活性（0.194 nmol/min/mg蛋白质）比男性（0.228 nmol/min/mg蛋白质）平均低15%（P = 0.03）。绝经前和绝经后妇女之间无差异。在接受FU治疗的患者中，发生副作用的风险与治疗前的DPD活性无关。FU相关毒性与FU全身暴露相关。治疗前DPD活性与FU全身清除率（Cl）之间的相关性较弱（n = 90，线性回归r = .31，P = .002）。治疗前DPD活动的患者谁需要减少剂量是没有显着不同的DPD活动的患者谁不需要剂量modification.Conclusion：从目前的研究中，它出现总DPD缺乏症是一种罕见的事件。尽管治疗前DPD活性不能作为改善FU剂量适应策略的有用指标，但严重DPD缺乏（< 0.100 nmol/min/mg蛋白质）的鉴定可能导致以显著降低的FU剂量开始治疗，甚至使用替代化疗方案。(C)1994年，美国临床肿瘤学会。
Purpose: We conducted a prospective study on a large set of cancer patients in an attempt to evaluate the incidence of complete or partial dihydropyrimidine dehydrogenase (DPD) deficiency as found in peripheral mononuclear cells (PMNC).Patients and Methods: One hundred eighty-five unselected consecutive cancer patients were included. The population consisted of 152 men (mean age, 62.1 years; range, 35 to 90) and 33 women (mean age, 59.2 years; range, 36 to 77). Sixty-eight were head and neck patients treated by a 5-day continuous infusion of fluorouracil (FU; starting dose, 1 g/m(2)/d, with dose adaptation based on pharmacokinetics) for which DPD activity was measured 2 to 3 days before FU administration 194 cycles analyzed). PMNC-DPD activity was measured by a radio-enzymatic assay using carbon-14-FU.Results: DPD activity in the entire population showed a unimodal distribution, which globally fits a gaussian distribution. Mean and median DPD activity values were 0.222 and 0.211 nmol/min/mg protein, respectively (range, 0.065 to 0.559). No total DPD deficiency was found. Multifactor analysis of variance showed that liver function (biologic evaluation) and age did not influence DPD activity, but that DPD activity was, on average, 15% lower in women (0.194 nmol/min/mg protein) then in men (0.228 nmol/min/mg protein) (P =.03). No difference was demonstrated between premenopausal and postmenopausal women. In patients treated with FU, the risk of developing side effects was not linked to pretreatment DPD activity. FU-related toxicity was linked to FU systemic exposure. The correlation between pretreatment DPD activity and FU systemic clearance (Cl) wets weak (n = 90, linear regression r = .31, P = .002). Pretreatment DPD activity in patients who required a dose reduction was not significantly different from DPD activity in patients who did not require dose modification.Conclusion: From the present study, it appears that total DPD deficiency is a rare event. Although pretreatment DPD activity cannot be a useful indicator for improving FU dose adaptation strategy, the identification of severe DPD deficiency (< 0.100 nmol/min/mg protein) could lead to starting the treatment with a markedly reduced FU dose or even to using an alternative chemotherapy regimen. (C) 1994 by American Society of Clinical Oncology.