Exceptional initial response of prostate cancer lung metastases to 225Ac-PSMA: A case report

Sathekge

2021

Prostate Cancer

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Despite advances in the treatment of localized prostate cancer, many patients progress to metastatic castration-resistant prostate cancer with limited median survival benefits, and significant morbidity. Therefore, efforts to explore new therapeutic modalities for metastatic castration-resistant prostate cancer are urgently needed. A theranostic approach in oncology is based on the principle of imaging a particular molecular target with a diagnostic radioisotope, and then substituting it with a therapeutic isotope to treat a patient who demonstrates sufficient target expression on diagnostic images. Radioisotope pairs are usually chosen in such a way that their physical and chemical properties are similar to ensure the therapeutic agent will be distributed in the same way as the diagnostic agent. This chapter outlines the most recent advances in the use of prostate specific membrane antigen (PSMA) in theranostics with emphasis on 177 Lu-PSMA, 225 Ac-PSMA and 223 Ra-dicloride. The clinical utility of these radioisotopes along with their limitations and future perspectives are discussed.

Section: Clinical Evidence With 225 Ac-psmasupporting

confidence: 83%

Theranostics in Metastatic Castrate Resistant Prostate Cancer

Sathekge

2021

Prostate Cancer

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“…Our group has routinely applied the concept of dose-de-escalation in which the activity of [ 225 Ac]Ac-PSMA-617 administered for therapy is titrated against tumor load as seen on [ 68 Ga]Ga-PSMA-11 PET/CT, which is done prior to each cycle of treatment [21,22,35,36]. This strategy has been effective in reducing the incidence and severity of xerostomia, the most troublesome side effects of [ 225 Ac]Ac-PSMA-617 therapy, in our practice.…”

Section: Discussionmentioning

confidence: 99%

Hematologic toxicity profile and efficacy of [225Ac]Ac-PSMA-617 α-radioligand therapy of patients with extensive skeletal metastases of castration-resistant prostate cancer

Lawal

Morgenstern

Eur J Nucl Med Mol Imaging

et al. 2022

Purpose: Actinium-225-labeled prostate-specific membrane antigen ([ 225 Ac]Ac-PSMA-617) is safe and effective in the treatment of metastatic castration-resistant prostate cancer (mCRPC). No study has specifically assessed its safety in patients with extensive skeletal metastases of mCRPC. We aimed to investigate the hematologic toxicity and efficacy of [ 225 Ac]Ac-PSMA-617 therapy in patients with extensive skeletal metastases of mCRPC. Methods:We retrospectively reviewed the medical record of patients treated with [ 225 Ac]Ac-PSMA-617 for mCRPC. We included patients with a superscan pattern of skeletal metastases and those with 20 or more multifocal sites of skeletal metastases on baseline [ 68 Ga]Ga-PSMA-11 PET/CT. We reviewed the levels of hemoglobin, white blood cell (WBC), and platelet prior to each cycle of treatment and determined the presence of impaired bone marrow function at baseline and the grade of toxicity in the hematologic parameters induced by treatment. We evaluated the predictors of hematologic toxicity using binary logistic regression analysis. We also determined the presence of renal dysfunction before or during treatment. We assessed response to treatment using prostate-specific antigen response and the progression-free survival (PFS) and overall survival (OS).Results: A total of 106 patients were included. Skeletal metastasis was in the superscan pattern in 34 patients (32.1%) and multifocal in 72 patients (67.9%). The median treatment cycle was 4 (range = 1-9). Ninety-eight patients (92.5%) had abnormal baseline hematologic parameters. One patient had grade 4 thrombocytopenia. Grade 3 anemia, leukopenia, and thrombocytopenia were seen in 1 (0.9%), 3 (2.8%), and 2 (1.9%) patients, respectively. Age, the number of treatment cycles, and the presence of renal dysfunction were significant predictors of hematologic toxicity. Eighty-five patients (80.2%) achieved PSA response. The median PFS and OS of the study population were 14:00 (95%CI: 8.15-19.86) months and 15.0 (95%CI: 12.8-17.2) months, respectively.Conclusions: [ 225 Ac]Ac-PSMA-617 induces a good anti-tumor effect in about 80% of patients with extensive skeletal metastases of mCRPC with a rare incidence of severe hematologic toxicity. Age, number of treatment cycles, and the presence of renal dysfunction were significant risk factors for hematologic toxicity of [ 225 Ac]Ac-PSMA-617 therapy.

“…In the last few years, different groups have reported insightful cases of treatment outcome of mCRPC with 225 Ac-PSMA-617, including remarkable response in patients with visceral metastases [80,81], long-lasting remission 225 Ac-PSMA-617 therapy [82], and some rare treatment-related side effects [83,84]. Table 2 summarizes clinical studies reporting the treatment outcome of mCRPC with 225 Ac-PSMA TAT.…”

Section: Current Evidence For the Efficacy Of 225 Ac-psma Therapy In Mcrpcmentioning

confidence: 99%

Global experience with PSMA-based alpha therapy in prostate cancer

Sathekge

Bruchertseifer

Eur J Nucl Med Mol Imaging

et al. 2021

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Purpose This review discusses the current state of prostate-specific membrane antigen (PSMA)-based alpha therapy of metastatic castration-resistant prostate cancer (mCRPC). With this in-depth discussion on the growing field of PSMA-based alpha therapy (PAT), we aimed to increase the interactions between basic scientists and physician–scientists in order to advance the field. Methods To achieve this, we discuss the potential, current status, and opportunities for alpha therapy and strategies, attempted to date, and important questions that need to be addressed. The paper reviews important concepts, including whom to treat, how to treat, what to expect regarding treatment outcome, and toxicity, and areas requiring further investigations. Results There is much excitement about the potential of this field. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other conventional therapies. Conclusion A better understanding of the strengths and limitations of PAT may help in creating an effective therapy for mCRPC and design a rational combinatorial approach to treatment by targeting different tumor pathways.