Optimal methionine-free diet duration for nitrourea treatment: A phase I clinical trial
Optimal methionine-free diet duration for nitrourea treatment: A phase I clinical trial
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DOI：
10.1080/01635580701525877
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发表时间：
2008-01-01
影响因子：
2.9
通讯作者：
Chollet, Philippe
中科院分区：
文献类型：
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作者：
Durando, Xavier;Thivat, Emilie;Chollet, Philippe
在动物模型中，甲硫氨酸（MET）限制与氯乙基亚硝基脲导致了实质性的改善。在此基础上，我们启动了饮食MET限制与氯乙基亚硝基脲（半胱氨酸）治疗复发性胶质瘤或转移性黑色素瘤患者的I期临床试验。我们的目的是：1）确定最大限度消除血浆MET的最佳无MET饮食持续时间; 2）评估这种关联的可行性。共有10名患者接受了4个周期的2周联合无MET饮食1，2，3或4连续天和半胱氨酸（60 mg/m2）。对于每个周期，测量血浆MET浓度、营养状况（体重、白蛋白、前白蛋白）和毒性。相反，饮食MET限制降低了餐后血浆MET浓度（上午12点），在无MET饮食的第1天最佳消耗为41%，而延长无MET饮食期没有影响。事实上，我们证明了无MET饮食和半胱氨酸治疗联合的可行性，即良好的饮食可接受性和良好的耐受性（营养状况和毒性）。基于这些结果，已经启动了II期临床试验，以测试1天无MET饮食与半胱氨酸治疗的关联的活性。
In animal models, methionine (MET) restriction in association with chloroethyinitrosoureas led to a substantial improvement. On this basis, we initiated a Phase I clinical trial of dietary MET restriction in association with chloroethylnitrosourea (cystemustine) treatment for patients with recurrent glioma or metastatic melanoma. Our purpose was 1) to determine the optimal MET-free diet duration for a maximum depletion of plasma MET and 2) to evaluate the feasibility of this association. A total of 10 patients received 4 cycles of 2 wk of an association of a MET-free diet of 1, 2, 3, or 4 consecutive days and cystemustine (60 mg/m(2)). For each cycle, plasma MET concentrations, nutritional status (weight, albumin, prealbumin) and toxicity were measured. Conversely, fed-state concentrations of plasma MET (12 AM) were reduced by dietary MET restriction, with an optimal depletion of 41 % at the 1st day of MET-free diet without effect of the extending MET-free diet period. Indeed, we demonstrated the feasibility, that is, good diet acceptability and good tolerance (nutritional status and toxicity), of the association of a MET-free diet and cystemustine treatment. Based on these results, a Phase II clinical trial has been initiated to test the activity of the association of a 1-day MET-free diet with cystemustine treatment.