Preliminary Evidence on Safety and Clinical Efficacy of Luteolin for Patients With Prostate Cancer Under Active Surveillance

Background: A need exists for effective treatments for prostate cancer (PCA) due its re-emergence following androgen deprivation therapy, a major clinical problem. In a previous study, we presented evidence on the chemopreventive and chemotherapeutic potential of luteolin, a flavonoid, in PCA including castration-resistant PCA. In this single-arm phase I study, we clinically examined the safety of the oral intake of luteolin in patients under active surveillance (AS). Methods: Between March and September in 2022, five patients with low-intermediate risk PCA and under AS were treated daily with 50 mg of oral luteolin for six months. We investigated the efficacy of oral luteolin in oncological outcomes and any adverse events (AEs) and examined prostate and blood specimens. Results: The median age of patients was 68 years (range: 60-78), and the median initial prostate-specific antigen level was 9.5 ng/mL. All patients were under AS without rapid progression. After treatment with luteolin, AEs were not noted in any patients for six months. All patients underwent a protocol biopsy. Of these, two patients showed a favorable response, one patient had stable disease, and two patients showed disease progression; robot-assisted radical surgery was subsequently performed for the latter. Immunohistochemical analysis revealed decreased expression of androgen receptor and NKX3.1 in noncancerous lesions after luteolin treatment. In addition, quantitative reverse transcription-PCR revealed that serum micro(mi)RNA expression in serum and prostate gland, including miR-29 and miR-30, tended to be upregulated after luteolin treatment compared with during the pretreatment phase. Conclusions: Our small phase I study of men with PCA suggests that daily treatment with 50 mg of an oral supplement of luteolin is safe and effective with regard to oncological outcomes, particularly in patients under AS.