Perillyl alcohol as a treatment for cancer: A systematic review

Abstract Background Cancer is the second leading cause of death in the world. Cancer treatment has many adverse effects, making the search for new therapeutic agents necessary. Objective this systematic review aimed to assess the efficacy of perillyl alcohol (POH) in the treatment of cancer based on the objective response (OR). Methods This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. The search was conducted in the PubMmed, Scopus, Web of Science, and Cochrane Library databases, and included clinical trials which reported in their results the anti-tumor activity of POH as an OR, and studies with isolated POH as treatment. The review excluded preclinical studies, in vitro trials, review articles, meta-analyses, abstracts, conference proceedings, editorials/letters, case reports, and studies assessing POH in other ways, not investigating it as an anticancer treatment. Data were extracted by two independent reviewers, using a table with pre-specified items. The risk of bias (RoB) in the included studies was assessed using the Cochrane risk of bias assessment tool. Results Thirteen studies were identified, 7 phase I and 6 phase II trials. Eleven studies administrated POH by oral route and 2 by inhalation. Ten studies reported adverse effects. Among the selected studies, the cancer types most studied were colorectal, ovarian, breast, and prostate cancers. None of the selected studies achieved clinical complete response (CR) after POH treatment, three achieved partial response (PR) and several reported stable disease (SD). Of the three which achieved PR, two used the inhalation route for POH. Conclusion The best evidence available shows that POH has little or no significant effect on objective response in different cancer types. However, the administration of POH by inhalation showed promising objective responses and outcomes. Taken together, these findings suggest a promising potential cytostatic effect of POH.