Prostate Cancer Research Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
Prostate Cancer Prostatic Dis. 2013 Mar;16(1):50-5. doi: 10.1038/pcan.2012.20. Epub 2012 Jun 12.
Pomegranate juice has been associated with PSA doubling time (PSADT) elongation in a single-arm phase II trial. This study assesses biological activity of two doses of pomegranate extract (POMx) in men with recurrent prostate cancer, using changes in PSADT as the primary outcome.
This randomized, multi-center, double-blind phase II, dose-exploring trial randomized men with a rising PSA and without metastases to receive 1 or 3 g of POMx, stratified by baseline PSADT and Gleason score. Patients (104) were enrolled and treated for up to 18 months. The intent-to-treat (ITT) population was 96% white, with median age 74.5 years and median Gleason score 7. This study was designed to detect a 6-month on-study increase in PSADT from baseline in each arm.
Overall, median PSADT in the ITT population lengthened from 11.9 months at baseline to 18.5 months after treatment (P < 0.001). PSADT lengthened in the low-dose group from 11.9 to 18.8 months and 12.2 to 17.5 months in the high-dose group, with no significant difference between dose groups (P = 0.554). PSADT increases >100% of baseline were observed in 43% of patients. Declining PSA levels were observed in 13 patients (13%). In all, 42% of patients discontinued treatment before meeting the protocol-definition of PSA progression, or 18 months, primarily due to a rising PSA. No significant changes occurred in testosterone. Although no clinically significant toxicities were seen, diarrhea was seen in 1.9% and 13.5% of patients in the 1- and 3-g dose groups, respectively.
POMx treatment was associated with ≥ 6 month increases in PSADT in both treatment arms without adverse effects. The significance of this on-study slowing of PSADT remains unclear, reinforcing the need for placebo-controlled studies in this patient population.
石榴汁与 PSA 倍增时间（PSADT）延长有关，这在一项单臂二期试验中得到了证实。本研究评估了两种剂量的石榴提取物（POMx）在复发性前列腺癌患者中的生物学活性，以 PSADT 的变化作为主要终点。
这是一项随机、多中心、双盲二期、剂量探索试验，将 PSA 升高且无转移的男性患者按基线 PSADT 和 Gleason 评分分层，随机分为 1 或 3 g POMx 组。患者（104 人）接受了长达 18 个月的治疗。意向治疗（ITT）人群 96%为白人，中位年龄 74.5 岁，中位 Gleason 评分为 7 分。该研究旨在检测每个治疗组中 PSADT 在研究期间从基线开始的 6 个月的增加。
总体而言，ITT 人群的中位 PSADT 从基线时的 11.9 个月延长至治疗后的 18.5 个月（P < 0.001）。低剂量组的 PSADT 从 11.9 个月延长至 18.8 个月，高剂量组从 12.2 个月延长至 17.5 个月，两组之间无显著差异（P = 0.554）。43%的患者 PSADT 增加超过基线的 100%。13 例（13%）患者 PSA 水平下降。共有 42%的患者在达到方案定义的 PSA 进展或 18 个月前因 PSA 升高而停止治疗。睾酮无显著变化。虽然未观察到明显的临床毒性，但分别有 1.9%和 13.5%的患者在 1 g 和 3 g 剂量组中出现腹泻。
POMx 治疗与两个治疗组中 PSADT 的至少 6 个月的增加相关，没有不良反应。这种 PSADT 研究中的减慢的意义尚不清楚，这强化了在这一患者人群中进行安慰剂对照研究的必要性。
