PHASE II TRIAL OF IV SODIUM PHENYLACETATE IN B CELL CLL

苯乙酸钠（NaPA）已被用于治疗先天性尿素合成缺陷或门脉系统性脑病引起的高氨血症的急性和慢性并发症多年。 1971年，有人提出NaPA是一种潜在的人类癌症治疗剂。 持续输注NaPA将允许研究这种关键氨基酸的长期消耗对B细胞的影响。 目前使用的药物通过类似的机制发挥作用，即，L-天冬酰胺酶只能在短时间内消耗氨基酸水平，并间歇给药。 事实上，L-天冬酰胺酶确实有一定的效果，即使有这些限制，提供了理论基础，继续研究与NaPA。 通过研究慢性淋巴细胞白血病（CLL）等疾病，我们可以很容易地通过简单的外周血和骨髓样本跟踪对肿瘤细胞的影响。 本研究的目的是1）了解B细胞恶性肿瘤（B-CLL和B细胞非霍奇金淋巴瘤）患者是否对静脉注射NaPA有反应; 2）了解这些恶性肿瘤患者接受NaPA治疗时的副作用。

Sodium phenulacetate (NaPA) has been used for years to treat acute and chronic complications of hyperammonemia from inborn errors of urea synthesis or portal systemic encephalopathy. In 1971, it was suggested that NaPA was a potential therapeutic agent for human cancers. Continuous infusion of NaPA will allow the study of the effects of prolonged depletion of this critical amino acid on B-cells. Currently utilized drugs that work by similar mechanisms, i.e., L-asparaginase, can deplete levels of amino acids for only a short time and are administered intermittently. The fact that L-asparaginase does have some effect, even with these limitations, provides rationale to pursue studies with NaPA. By studying disease such as chronic lymphocytic leukemia (CLL), we can easily follow the effects on the tumor cells with simple peripheral blood and bone marrow samples. The goals of this study are 1) to learn if patients with B-cell malignancies (B-CLL and B-cell non-Hodgkin's lymphoma) respond to intravenous NaPA; and 2) to learn the side effects profile in patients with these malignancies when treated with this schedule of NaPA.