PHASE I STUDY OF PERILLYL ALCOHOL IN PATIENTS WITH REFRACTORY MALIGANCIES

单萜衍生物已被证明可以预防乳腺癌的发生 并使已建立的肿瘤分化和消退， 啮齿动物模型。这种抗癌活性的机制尚未被证实。 建立，但可能与选择性抑制 小G蛋白的异戊二烯化，包括ras结构-活性 柠檬烯衍生的单萜的研究已经鉴定出紫苏醇 作为一种更有效的衍生物。 紫苏醇的毒理学研究 表明剂量相关虚弱、胃肠道副作用 氮质血症、贫血和白细胞增多是最显著的副作用。 我们正在进行一项研究，以确定紫苏醇的最佳剂量 一天三次长期服用 迄今为止，有6名患者 接受治疗，患者接受的最长持续时间为16周 治疗 三名患者接受了第一剂量水平的 1600 mg/m2/天。 观察到的毒性包括轻度恶心， 轻微疲劳和排便习惯轻微改变（频率增加 和松散的一致性）。第二天已经有三名患者入组 剂量水平2100 mg/m2/天，正在对这些患者进行评估。

Monoterpene derivates have been shown to prevent mammary carcinogenesis and to produce differentiation and regression of established tumors in rodent models. The mechanism for this anticancer activity has not yet been established but may be related to selective inhibition of the isoprenylation of small G proteins, including ras Structure-activity studies of limonene-derived monoterpenes have identified perillyl alcohol as a more potent derivative. Toxicology studies of perillyl alcohol indicate that dose-related asthenia, gastrointestinal side-effects, azotemia and anemia and leukocytosis are the most prominent side-effects. We are conducting a study to define the optimal dose of perillyl alcohol when given three times daily on a chronic basis. To date 6 patients have been treated, with 16 weeks the longest duration a patient received treatment. Three patients have been treated on the first dose level of 1600mg/m2/day. The toxicities observed have consisted of mild nausea, slight fatigue and a minor alteration in bowel habit (increased frequency and looser consistency). Three patients have been enrolled on the second dose level 2100mg/m2/day and assessment of these patients is ongoing.