Phase I clinical trial of i.v. ascorbic acid in advanced malignancy
Phase I clinical trial of i.v. ascorbic acid in advanced malignancy
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DOI：
10.1093/annonc/mdn377
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发表时间：
2008-11-01
影响因子：
50.5
通讯作者：
Miller, W. H., Jr.
中科院分区：
文献类型：
--
作者：
Hoffer, L. J.;Levine, M.;Miller, W. H., Jr.
背景：抗坏血酸是一种广泛使用且有争议的替代癌症治疗方法。在毫摩尔浓度下，它对许多癌细胞系具有选择性细胞毒性，并且当单独施用或与其他药剂一起施用时具有体内抗癌活性。我们进行了一个剂量发现阶段I和药物动力学研究静脉注射抗坏血酸在晚期malignancy.Patients和方法：晚期癌症或血液恶性肿瘤患者被分配到连续队列输注0.4，0.6，0.9和1.5克抗坏血酸/公斤体重three times weekly.Results：不良事件和毒性是最小的在所有剂量水平。没有病人有一个客观的抗癌responsibility.Conclusions：高剂量静脉注射抗坏血酸耐受性良好，但未能证明抗癌活性时，给药与先前治疗的晚期恶性肿瘤患者。这种方法的前景可能在于与细胞毒性或其他氧化还原活性分子的组合。
Background: Ascorbic acid is a widely used and controversial alternative cancer treatment. In millimolar concentrations, it is selectively cytotoxic to many cancer cell lines and has in vivo anticancer activity when administered alone or together with other agents. We carried out a dose-finding phase I and pharmacokinetic study of i.v. ascorbic acid in patients with advanced malignancies.Patients and methods: Patients with advanced cancer or hematologic malignancy were assigned to sequential cohorts infused with 0.4, 0.6, 0.9 and 1.5 g ascorbic acid/kg body weight three times weekly.Results: Adverse events and toxicity were minimal at all dose levels. No patient had an objective anticancer response.Conclusions: High-dose i.v. ascorbic acid was well tolerated but failed to demonstrate anticancer activity when administered to patients with previously treated advanced malignancies. The promise of this approach may lie in combination with cytotoxic or other redox-active molecules.