Monoterpenes have a wide range of anticancer activity in rodent and in in vitro models. These activities span prevention and treatment of multiple cancer types. The most extensively studied and impressive results have been the ability of dietary monoterpene (perillyl alcohol) to cause the complete regression of the majority of mammary carcinomas in the same rodent models which led to the development of tamoxifen. In addition, monoterpenes show a diverse array of metabolic, cellular, and molecular activities both in vitro and in vivo, including inhibition of cellular proliferation, induction of differentiation and apoptosis and differential gene regulation. Finally, preliminary Phase I testing suggests that perillyl alcohol will be well tolerated in cancer patients. The primary goal of this project is to assess the clinical effectiveness of daily perillyl alcohol in refractory metastatic breast cancer patients enrolled on a Phase II study. Perillyl alcohol will be given in three divided daily oral doses every day. Two additional pilot studies will be performed, in conjunction with the Phase II study, based on the hypothesis that a major mechanism underlying the antitumor activity of monoterpenes is the induction of the mannose 6-phosphate (M6P)/insulin-like growth factor II (IGF-II) receptor. Biomarkers related to these hypothesized mechanisms such as serum TGF-beta will be examined as potential intermediate endpoints for monoterpene (perillyl alcohol) clinical activity. Data will also be collected to evaluate the potential of the somatic genetic loss of the M6P/IGF-II receptor, a recently identified suppressor gene, as a negative predictor of clinical responsiveness to monoterpenes.
| Bailey, Howard H; Attia, Steven; Love, Richard R et al. (2008) Phase II trial of daily oral perillyl alcohol (NSC 641066) in treatment-refractory metastatic breast cancer. Cancer Chemother Pharmacol 62:149-57 |
