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.
Showing the most recent 10 out of 343 publications
