Relationship between cytochrome 3A activity, inflammatory status and the risk of docetaxel-induced febrile neutropenia: a prospective study
Relationship between cytochrome 3A activity, inflammatory status and the risk of docetaxel-induced febrile neutropenia: a prospective study
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DOI：
10.1093/annonc/mdl321
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发表时间：
2007-01-01
影响因子：
50.5
通讯作者：
Goldwasser, F.
中科院分区：
文献类型：
--
作者：
Alexandre, J.;Rey, E.;Goldwasser, F.
背景：我们假设与癌症相关的炎症可能会增加多西他赛(DCX，泰素帝)引起的中性粒细胞减少症(FN)的风险，这是通过影响DCX的暴露和组织敏感性而实现的。在DCX第一周期前，静注0.015 mg/kg后4h，单次测定咪达唑仑血药浓度，测定细胞色素P4503A活性。丸剂。第一周期75-100 mg/m(2)DCX后，采用有限抽样策略估计清除量和浓度-时间曲线下面积(AUC)。结果：在56例可评估的患者中，有7例(13%)在第一周期后发生FN。在单因素分析中，高咪达唑仑浓度和游离DCX AUC与严重的中性粒细胞减少和FN相关。除了DCX暴露的相关参数外，FN的风险还与PS差、基线淋巴细胞减少和肺癌相关，而高铁蛋白水平作为炎症状态的指标，达到了临界意义(P=0.07)。经多因素分析，总DCX、AUC和基线淋巴细胞减少与FN相关。咪达唑仑浓度高与铁蛋白水平升高相关(r=0.32；P=0.02)。结论：在DCX开始前，应将炎症状态和淋巴细胞计数纳入受益/风险比的评估。
Background: We hypothesized that cancer-related inflammation might increase the risk of febrile neutropenia (FN) induced by docetaxel (DCX, Taxotere), by both affecting the exposure to DCX and the tissue sensitivity.Patients and methods: Advanced cancer patients with normal liver function, performance status (PS) < 3, were included. Cytochrome P450 3A (CYP 3A) activity was estimated before the first cycle of DCX by a single determination of midazolam plasma concentration, 4 hours after 0.015 mg/kg i.v. bolus. Following the first cycle of 75-100 mg/m(2) DCX, clearance and area under the concentration versus time curve (AUC) were estimated using a limited sampling strategy.Results: Among 56 assessable patients, 7 FNs occurred after first cycle (13%). In univariate analysis, high midazolam concentration and free DCX AUC were associated with severe neutropenia and FN. In addition to DCX exposure-related parameters, the risk of FN was also correlated with poor PS, baseline lymphopenia and lung cancer, while high ferritin level, indicator of an inflammatory state, reached borderline significance (P = 0.07). By multivariate analysis, total DCX AUC and baseline lymphopenia were associated with FN. High midazolam concentration was correlated with elevated ferritin level (r = 0.32; P = 0.02).Conclusion: Inflammatory status and lymphocyte count should be included in the evaluation of the benefice/risk ratio before the initiation of DCX.