225Ac-Prostate-Specific Membrane Antigen Therapy for Castration-Resistant Prostate Cancer

Abstract

Purpose Prostate-specific membrane antigen (PSMA)–targeted therapies are among the current promising treatments. We present our preliminary results on the use of 225Ac-PSMA therapy in patients with metastatic castration-resistant prostate cancer as a single center. Methods Twelve advanced stage metastatic castration-resistant prostate cancer patients who received 225Ac-PSMA therapy were recruited in this retrospective study. Patients were treated with 225Ac-PSMA therapy every 8 weeks, and prostate-specific antigen (PSA) response was analyzed. Meanwhile, overall survival (OS) and progression-free survival (PFS) were estimated. Hematological and nonhematological adverse effects were recorded before and at 8 weeks after the last treatment cycle. Results In total, 25 cycles of 225Ac-PSMA were administered to 12 patients. The pretreatment median PSA level was 129 ng/mL. After the first cycle of therapy, any PSA response was observed in 9 of 12 patients, whereas 6 of them had biochemical response of >50%. Four of 12 patients reached the best PSA response after the first treatment cycle, whereas 3 patients after the second and 2 patients after the third cycle. The median PFS and OS were 4 and 10 months, respectively. For patients with any PSA response after the first cycle, OS was found to be higher despite without any statistical significance (10 vs 4 months; P = 0.301) when compared with the nonresponsive group. No significant difference was encountered in terms of adverse effect in the pretreatment and posttreatment era. Conclusions Our preliminary results are encouraging, especially patients who had PSA response after the first cycle of 225Ac-PSMA therapy.

Advances in 177Lu-PSMA and 225Ac-PSMA Radionuclide Therapy for Metastatic Castration-Resistant Prostate Cancer

“…Treatment responses of 225 Ac-PSMA RNT in patients with mCRPC have also been evaluated by several other clinical research groups [ 20 , 21 , 22 , 23 , 27 ]. In the majority of studies, patients were treated with [ 225 Ac]Ac-PSMA-617.…”

“…However, the survival benefit is limited to only a few months [ 5 , 6 ]. In the past few years, promising results have been reported in patients treated with beta and alpha radionuclide therapy (RNT) using the prostate-specific membrane antigen (PSMA) labeled with lutetium-177 (Lu-177) or actinium-225 (Ac-225), respectively [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. These treatments provide patients with mCRPC new options to improve survival and quality of life.…”

Response to RL‐225Ac in prostate cancer: Effect of prior treatment with RL‐177Lu: A systematic review of the literature

“…Five articles 25,27,28,30,36 had data about cancer control (e.g., PSA response) and could be included in this analysis. Table 2 shows an overview of the PSA response categories (any decline, >25% decline, >50% decline, and progression).…”

Delayed Nephrotoxicity After 225Ac-PSMA-617 Radioligand Therapy

“…Targeted therapy with 225 Ac-PSMA-617 RLT (radioligand therapy) has shown promising efficacy in metastatic castration-resistant prostate cancer patients refractory to approved treatment options. [1][2][3] Being an α-particle emitter with a short tissue range, the treatment is usually considered safe with no major acute and subacute AEs. 2,4 However, data on long-term AEs are currently limited.…”