TPS273 Background: Epidemiological studies suggest that diet can impact the incidence, progression, and response to treatment of several malignancies, including prostate cancer (PCa). Our group has previously reported that dietary protein restriction has a significant anti-tumor effect in patient-derived xenograft models of PCa ( Fontana L et al Oncotarget 2013 PMID: 24353195 ). We have also recently shown that caloric restriction through alternate-day fasting (ADF) reduces androgen receptor (AR) expression and signaling and enhances the antitumor activity of the AR antagonist enzalutamide in multiple mouse models of PCa. Nutrient starvation via ADF predominantly decreases AR mRNA translation at the elongation stage due to amino acid limitation. Thus, we propose that amino acid limitation through intermittent fasting (IF) may enhance AR-targeted therapy. Methods: Thirty adults (≥18 years) with histologically confirmed prostate cancer and measurable/evaluable disease (i.e. PSA) receiving androgen receptor signaling inhibitors (ARSI) will be enrolled at the University at Buffalo/Great Lakes Cancer Care. This is a single center, longitudinal study to assess the feasibility of IF with or without a plant-based diet. Patients will undergo 16/8hs periods of fasting/eating and will be also offered to undergo a plant-based diet. Each cycle will have a duration of 28 days. Diet intervention will last for at least 3 cycles. Primary endpoints include enrollment, dropout, and dietary compliance rates measured by self-reports. Secondary objectives will assess whether IF (and optionally plant-enriched diet) reduces common toxicities as compared to historical data, the safety and tolerability of the combination of this dietary intervention using NCI CTCAE throughout the intervention period, and preliminary evidence of clinical efficacy including radiological and/or biochemical response (partial + complete), and progression-free survival. Feasibility will be assessed via self-reported dietary logs (MyFitnessPal), interviews, and retention metrics. Explorative objectives will include biomarker analyses (e.g., FGF21, IGF-1, insulin, CRP, leptin, glucose, cytokines) which will be conducted at baseline, mid-treatment, and post-treatment; stool samples will be analyzed for bacterial DNA. Body composition (DEXA/InBody) and patient-reported outcomes (appetite, mood, stress, quality of life) will be measured at predefined intervals. Overall, we hypothesize that IF plus a plant-based diet will be feasible and safe in patients undergoing ARSI with preliminary signals of improved clinical response and tolerability Findings from this pilot trial will inform the design of larger randomized studies investigating IF as adjunctive therapy for PCa patients receiving ARSI. The study is open to accrual with 7 patients enrolled at the time of submission. Clinical trial information: NCT06172283 .
Pili et al. (Sun,) studied this question.