title: Calcitriol in Combination Therapy for Prostate Cancer: Pharmacokinetic and Pharmacodynamic Interactions.
abstract: Epidemiological studies indicate that vitamin D insufficiency could have an etiological role in prostate cancer. In addition, calcitriol, used in combination with currently available drugs, has the potential to potentiate their anticancer effects or act synergistically by inhibiting distinct mechanisms involved in prostate cancer growth. Clinical data have not yet provided sufficient evidence to demonstrate benefit of vitamin D due to the limited and underpowered studies that have been published to date. Here, we review the preclinical and clinical studies that describe the activity of calcitriol, applied either alone or in combination and assessed the mechanistic basis of pharmacodynamic and pharmacokinetic interactions with calcitriol. Important considerations for calcitriol use in combination therapy with respect to safety and clinical outcomes have been discussed. Many of these combinations have therapeutic potential for the treatment of several cancer types and it is anticipated that future clinical research will put emphasis on well‑designed clinical trials to establish efficacy.
authors.affiliation: 1. The Vancouver Prostate Centre at Vancouver General Hospital, Vancouver, BC, Canada; 2. Department of Experimental Medicine, University of British Columbia, Vancouver, B.C, Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ben-Eltriki
authors.affiliation: 4. Department of Biopharmaceutical Sciences, College of Pharmacy at Roosevelt University, Schaumburg, IL, USA.
authors.forename: Subrata
authors.initials: S
authors.lastname: Deb
authors.affiliation: 1. The Vancouver Prostate Centre at Vancouver General Hospital, Vancouver, BC, Canada; 3. Department of Urologic Sciences, University of British Columbia, Vancouver, B.C, Canada.
authors.forename: Emma S Tomlinson
authors.initials: ES
authors.lastname: Guns
keywords: CYP enzymes; Calcitriol; metabolism; pharmacodynamics; pharmacokinetics; prostate cancer; vitamin D receptor