BACKGROUND Radioligand therapy with [177Lu]Lu-PSMA-617 is efficacious for the treatment of patients with metastasized castration-resistant prostate cancer (mCRPC). Various studies have evaluated the efficacy and safety of [177Lu]Lu-PSMA-617 using a dose of 6.0 GBq and an 8-week therapy interval. However, the first prospective phase III trial (VISION) plans to use an elevated cumulative dose by applying 7.5 GBq in a 6-week interval. The aim of the present study was to compare safety and efficacy of the two aforementioned [177Lu]Lu-PSMA-617 therapy regimes (7.5 GBq every 6 weeks vs. 6.0 GBq every 8 weeks). METHODS A total number of 78 consecutive patients with mCRPC and a history of first-line chemotherapy were included in this retrospective analysis. The outcome of patients treated with 6.0 GBq [177Lu]Lu-PSMA-617 per cycle (n = 37) were compared with those treated with 7.5 GBq (n = 41) per cycle. The median therapy intervals were 8.4 weeks (6.0 GBq group) vs. 6.5 (7.5 GBq group). PSA response, PSA progression-free survival (PSA-PFS), overall survival, and adverse events were evaluated and compared between both groups. Chi-squared test, Kaplan Meier estimates, Cox regression, and log-rank test were used. The highest decline from pretherapeutic PSA levels was measured as percentage (best PSA response) and compared between groups by Wilcoxon test. RESULTS There was no significant difference comparing the rate of > 50% PSA decline or best PSA response between the 6.0 GBq and 7.5 GBq group (35% vs. 54%, p = 0.065; and - 40.2% vs. - 57.8%, p = 0.329). The median estimated survival and PSA-PFS did not significantly differ between the 6.0 GBq and 7.5 GBq groups as well (11.3 vs. 12.7 months, p = 0.384; and 9.5 vs. 12.3 months, p = 0.258). There was no significant difference regarding the change of kidney, liver, and blood cell parameters under therapy between the treatment groups. CONCLUSION Higher cumulated doses of [177Lu]Lu-PSMA-617 were well tolerated and caused no significantly increased rate of adverse reactions. Moreover, 7.5 GBq of [177Lu]Lu-PSMA-617 every 6 weeks causes slightly higher, though not statistically significant, response rates and seems therefore to be the preferable treatment regime. However, future studies are needed to elucidate the dose-related efficacy of [177Lu]Lu-PSMA-617 as a way to personalized medicine.

中文翻译：

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在mCRPC中使用[177Lu] Lu-PSMA-617进行放射配体治疗：VISION之前的单中心分析。

背景技术[177Lu] Lu-PSMA-617的放射配体疗法对于治疗转移性去势抵抗性前列腺癌（mCRPC）患者是有效的。各种研究使用6.0 GBq的剂量和8周的治疗间隔评估了[177Lu] Lu-PSMA-617的疗效和安全性。但是，第一个前瞻性III期试验（VISION）计划通过在6周的间隔中应用7.5 GBq来使用升高的累积剂量。本研究的目的是比较上述两种[177Lu] Lu-PSMA-617治疗方案的安全性和有效性（每6周7.5 GBq与每8周6.0 GBq）。方法回顾性分析了78例连续的mCRPC患者和一线化疗史。用6治疗的患者的结果。将每个周期0 GBq [177Lu] Lu-PSMA-617（n = 37）与每个周期7.5 GBq（n = 41）处理的样本进行比较。中位治疗间隔为8.4周（6.0 GBq组）与6.5周（7.5 GBq组）。评估并比较两组的PSA反应，PSA无进展生存期（PSA-PFS），总生存期和不良事件。使用卡方检验，Kaplan Meier估计，Cox回归和对数秩检验。相对于治疗前PSA水平的最高下降以百分数（最佳PSA反应）衡量，并通过Wilcoxon检验比较各组之间的差异。结果在6.0 GBq和7.5 GBq组之间比较PSA下降> 50％或最佳PSA响应率没有显着差异（35％vs. 54％，p = 0.065；以及-40.2％vs.-57.8％，p = 0.329）。6.0 GBq组和7.5 GBq组之间的中位估计生存期和PSA-PFS也无显着差异（11.3 vs. 12.7个月，p = 0.384； 9.5 vs. 12.3个月，p = 0.258）。治疗组之间在肾脏，肝脏和血细胞参数变化方面无显着差异。结论较高的[177Lu] Lu-PSMA-617累积剂量耐受性良好，并且未引起不良反应发生率显着增加。此外，每6周7.5 GBq的[177Lu] Lu-PSMA-617引起的缓解率略高，尽管在统计学上并不显着，因此似乎是较好的治疗方案。但是，需要进一步的研究来阐明[177Lu] Lu-PSMA-617的剂量相关功效，作为个性化药物的一种方法。384; 和9.5和12.3个月相比，p = 0.258）。治疗组之间在肾脏，肝脏和血细胞参数变化方面无显着差异。结论较高的[177Lu] Lu-PSMA-617累积剂量耐受性良好，并且未引起不良反应发生率显着增加。此外，每6周7.5 GBq的[177Lu] Lu-PSMA-617引起的缓解率略高，尽管在统计学上并不显着，因此似乎是较好的治疗方案。但是，需要进一步的研究来阐明[177Lu] Lu-PSMA-617的剂量相关功效，作为个性化药物的一种方法。384; 和9.5和12.3个月相比，p = 0.258）。治疗组之间在肾脏，肝脏和血细胞参数变化方面无显着差异。结论较高的[177Lu] Lu-PSMA-617累积剂量耐受性良好，并且未引起不良反应发生率显着增加。此外，每6周7.5 GBq的[177Lu] Lu-PSMA-617引起的应答率略高，尽管在统计学上不显着，因此似乎是较好的治疗方案。但是，需要进一步的研究来阐明[177Lu] Lu-PSMA-617的剂量相关功效，作为个性化药物的一种方法。结论较高的[177Lu] Lu-PSMA-617累积剂量耐受性良好，并且未引起不良反应发生率显着增加。此外，每6周7.5 GBq的[177Lu] Lu-PSMA-617引起的缓解率略高，尽管在统计学上并不显着，因此似乎是较好的治疗方案。但是，需要进一步的研究来阐明[177Lu] Lu-PSMA-617的剂量相关功效，作为个性化药物的一种方法。结论较高的[177Lu] Lu-PSMA-617累积剂量耐受性良好，并且未引起不良反应发生率显着增加。此外，每6周7.5 GBq的[177Lu] Lu-PSMA-617引起的缓解率略高，尽管在统计学上并不显着，因此似乎是较好的治疗方案。但是，需要进一步的研究来阐明[177Lu] Lu-PSMA-617的剂量相关功效，作为个性化药物的一种方法。