INTRODUCTION AND OBJECTIVES: The use of histone deacetylase inhibitors (HDACIs) in treating Castrate Resistant Prostate Cancer is well studied. We have previously published the beneficial effects of treating Bladder as well as Prostate cancer (CaP) in animal models with Valproic acid (VPA), a type I HDACI. Docosahexaenoic acid (DHA), an u‐3 fatty acid, is a primary structural component of the human brain, skin, sperm, testicles and retina. Fish oil, a popular nutritional supplement, is a major source of DHA. Over two decades of research show favorable effects of DHA on bone health, as well as a chemo‐sensitizing agent in treating cancer. Here we report an interim analysis of a randomized, controlled phase II study of VPA in patients with non‐metastatic biochemical progression of (BCR) CaP, and the utility of combining DHA with VPA in potentially reducing side effects. METHODS: Patients with non‐metastatic BCR CaP were screened for eligibility and randomized into either observation or VPA (oral, twice daily) arms. Serum VPA and PSA levels were monitored biweekly and monthly. We also investigated methods of minimizing the side effects of VPA while maintaining efficacy. RESULTS: Treatment with VPA resulted in an increased PSA doubling time (PSADT) in patients from 4.02 to 40.67 months, while the PSADT in the control group stayed relatively unchanged at 6.34 to 6.95 months. However, the treatment group suffered from debilitating fatigue and lethargy at the dose required for effective treatment. As such we investigated options of reducing the VPA dose while maintaining efficacy. Both in vitro and in a mouse model we demonstrate that combining VPA with DHA has a greater efficacy. In the in vitro model we show that in the combination we can reduce the dose of VPA by half and still maintain similar efficacy. Also chronic treatment with the combination had a much greater effect on cell kill as opposed to acute treatment. Moreover, folic acid, another common supplement, enhances cell kill by the combination. CONCLUSIONS: Based on our studies VPA could be used in combination with DHA, a supplement, to delay or even prevent the use of hormone therapy in prostate cancer patients with BCR. In addition, both clinicians and patients should be made aware of the effects of dietary supplements, as they can positively or potentially negatively affect the efficacy of certain drugs. (Figure presented).
Chowdhury, W. H., O’James, A.-B., Sidana, A., Goyal, J., Oh, D., Todd, G. I., … Rodriguez, R. (2017). PD37-08 ENHANCING THE EFFICACY OF VALPROIC ACID IN PROSTATE CANCER CELLS WITH NUTRITIONAL SUPPLEMENTS. Journal of Urology, 197(4S). https://doi.org/10.1016/j.juro.2017.02.1570