Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
Department of Radiology, DIAKOVERE Friederikenstift, Hannover, Germany.
Prostate. 2020 May;80(8):619-631. doi: 10.1002/pros.23974. Epub 2020 Mar 18.
Corticosteroids alone or in combination therapy are associated with favorable biochemical responses in metastatic castration-resistant prostate cancer (mCRPC). We speculated that the intermittent addition of dexamethasone may also enhance the antitumor effect of radioligand therapy (RLT) with Lu-prostate-specific membrane antigen (PSMA)-617.
Seventy-one patients with mCRPC were treated with 1 to 5 cycles of Lu-PSMA-617 (6.0-7.4 GBq per cycle) at 6 to 8 weeks intervals. Based on the clinical decision (eg, in the case of vertebral metastases), 56% of patients received 4 mg of dexamethasone for the first 5 days of each cycle. Biochemical response rates, PSA decline and progression-free survival (PFS) were analyzed after one, three, and five cycles of RLT.
PSA response rates were not significantly different between patients receiving Lu-PSMA-617 plus dexamethasone and those receiving Lu-PSMA-617 alone after one, three, and five cycles (33% vs 39%, P = .62; 45% vs 45%, P = 1.0; and 38% vs 42%, P = .81). However, there was a nonsignificant trend for a more pronounced PSA decline in patients with bone metastases receiving adjunct dexamethasone (-21% ± 50% vs +11% ± 90%, P = .08; -21% ± 69% vs +22% ± 116%, P = .07; -13% ± 76% vs +32% ± 119%, P = .07). Median PFS tended to be longer in patients with bone metastases receiving Lu-PSMA-617 plus dexamethasone (146 vs 81 days; hazard ratio: 0.87 [95% confidence interval: 0.47-1.61]; P = .20). Multiple regression analysis showed that age (P = .0110), alkaline phosphatase levels (P = .0380) and adjunct dexamethasone (P = .0285) were independent predictors of changes in PSA in patients with bone metastases.
We observed high response rates to Lu-PSMA-617 RLT in men with mCRPC. The short-term addition of dexamethasone to Lu-PSMA-617 had no striking antitumor effect but might enhance biochemical responses in patients with bone metastases. Future trials are warranted to test this hypothesis in a prospective setting.
单独使用皮质类固醇或联合治疗与转移性去势抵抗性前列腺癌（mCRPC）的有利生化反应相关。我们推测，间歇性添加地塞米松也可能增强 Lu-前列腺特异性膜抗原（PSMA）-617 放射性配体治疗（RLT）的抗肿瘤作用。
71 例 mCRPC 患者每 6-8 周接受 1-5 个周期的 Lu-PSMA-617（每个周期 6.0-7.4GBq）治疗。根据临床决策（例如，在存在脊椎转移的情况下），56%的患者在每个周期的前 5 天接受 4mg 地塞米松。在 RLT 进行一个、三个和五个周期后，分析生化反应率、PSA 下降和无进展生存期（PFS）。
在一个、三个和五个周期后，接受 Lu-PSMA-617 加地塞米松治疗的患者与单独接受 Lu-PSMA-617 治疗的患者之间的 PSA 反应率无显著差异（33%对 39%，P=0.62；45%对 45%，P=1.0；38%对 42%，P=0.81）。然而，在接受辅助地塞米松治疗的骨转移患者中，PSA 下降更为明显，这一趋势无统计学意义（-21%±50%对+11%±90%，P=0.08；-21%±69%对+22%±116%，P=0.07；-13%±76%对+32%±119%，P=0.07）。在接受 Lu-PSMA-617 加地塞米松治疗的骨转移患者中，中位 PFS 倾向于更长（146 天对 81 天；风险比：0.87[95%置信区间：0.47-1.61]；P=0.20）。多因素回归分析显示，年龄（P=0.0110）、碱性磷酸酶水平（P=0.0380）和辅助地塞米松（P=0.0285）是骨转移患者 PSA 变化的独立预测因素。
我们观察到 Lu-PSMA-617 RLT 治疗 mCRPC 男性的高反应率。Lu-PSMA-617 短期加用地塞米松无明显抗肿瘤作用，但可能增强骨转移患者的生化反应。需要进一步的前瞻性试验来检验这一假设。
