A Phase II Trial Using Grape Seed Extract for Prostate Cancer Patients With Nonmetastatic Prostate‐Specific Antigen Progression After Local Therapy

ABSTRACT Prostate cancer (PCa) is a major cause of cancer‐related death among American men. While androgen deprivation therapy (ADT) is commonly used in the treatment of rising prostate‐specific antigen (PSA) levels after primary therapy, its adverse systemic side effects support exploring low‐impact treatment options during the observation period of nonmetastatic PSA‐only progression. Grape seed extract (GSE) is a nontoxic phytochemical that has shown anti‐PCa efficacy in preclinical studies. Herein, we report the results of a completed Phase II clinical trial (CT.gov‐NCT03087903) which investigated the effect of GSE in patients with PSA‐only recurrence after maximum local therapy for PCa. Study endpoints included PSA response (defined as a ≥ 30% increase in model‐estimated PSA‐DT) and change in PSA velocity. Forty‐one patients were given 150 mg of GSE orally twice daily (Leucoselect‐Phytosome formulation with increased bioavailability) for 12 months or until PSA‐DT ≤ 3 months. Mixed‐effects spline modeling of longitudinal PSA demonstrated a modest increase in PSA‐DT following treatment initiation. Most patients experienced some degree of increase in model‐estimated PSA‐DT, with 37% of those patients meeting the primary endpoint of ≥ 30% increase in PSA‐DT. GSE demonstrated a favorable safety profile. Although further validation is warranted, the observed changes in PSA‐DT indicate that GSE may contribute to delaying PCa progression. The therapeutic effect appeared to be more pronounced among patients with higher baseline PSA and testosterone levels, suggesting that these factors may influence responsiveness to treatment. These promising findings support further investigation to identify patient populations most likely to benefit from GSE intervention. Trial Registration: ClinicalTrials.gov site (CT.gov‐NCT03087903).