Health-related quality-of-life outcomes with actinium-225-prostate-specific membrane antigen-617 therapy in patients with heavily pretreated metastatic castration-resistant prostate cancer

Satapathy, Sujata; Mittal, Bhagwant Rai; Sood, Anil K.; Das, Chandan Krushna; Singh, Shrawan Kumar; Mavuduru, Ravimohan; Bora, Girdhar S.

doi:10.4103/ijnm.ijnm_130_20

Cited by 21 publications

(25 citation statements)

References 19 publications

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“…For 225 Ac-augmentation, we applied a mean activity of 33 kBq/kg BW, which is one third of the recommended activity for the application of [ 225 Ac]Ac-PSMA-617 as monotherapy [57]. A prospective study on [ 225 Ac]Ac-PSMA-617 monotherapy by Yadav et al reported grade 1/2 xerostomia in 29% of patients [25], and other retrospective studies observed considerably higher rates [26][27][28][29]. However, it should be noted that in these studies, some patients received more than two cycles.…”

Section: Discussionmentioning

confidence: 99%

“…PSMA-RLT using alpha emitters as actinium-225 ( 225 Ac, half-life: 9.9 d), whose particles (E = 5.8 MeV) possess a shorter tissue range (<0.1 mm) and a higher LET (>50 keV/µm) [21,22], may have an advantage in comparison to PSMA-RLT with beta emitters. Recently, clinical studies using 225 Ac-labeled PSMA-ligands ([ 225 Ac]Ac-PSMA-617 or [ 225 Ac]Ac-PSMA-I&T) have reported remarkable therapeutic results [23][24][25][26][27][28][29][30]. However, the stronger radiobiological effect of alpha particles also has implications to the organs at risk.…”

Section: Of 14mentioning

confidence: 99%

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Efficacy and Safety of [225Ac]Ac-PSMA-617 Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Highly Advanced mCRPC with Poor Prognosis

et al. 2021

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The use of 225Ac in prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), either as monotherapy or in combination with 177Lu, is a promising therapy approach in patients with metastatic castration-resistant prostate carcinoma (mCRPC). In this study, we report the efficacy and safety of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in 177Lu-naive mCRPC patients (n = 15) with poor prognosis (presence of visceral metastases, high total tumor burden with diffuse bone metastases or a short PSA doubling time of <2 months). Biochemical (by PSA serum value) and molecular imaging response (by [68Ga]Ga-PSMA-11 PET/CT) was assessed after two cycles of [177Lu]Lu-PSMA-617 RLT, with at least one [225Ac]Ac-PSMA-617 augmentation. In addition, PSA-based progression-free survival (PSA-PFS), overall survival (OS) and toxicity (according to CTCAE) were analyzed. We observed a biochemical- and molecular imaging-based partial remission in 53.3% (8/15) and 66.7% (10/15) of patients, respectively. The median PSA-PFS and OS was 9.1 and 14.8 months, respectively. No serious acute adverse events were recorded. Two out of fifteen patients experienced grade 3 anemia. No other grade 3/4 toxicities were observed. RLT-related xerostomia (grade 1/2) was recorded in 2/15 patients. Our data showed a high clinical efficacy with a favorable side effects profile of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in this highly challenging patient cohort.

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Section: Discussionmentioning

confidence: 99%

Section: Of 14mentioning

confidence: 99%

Efficacy and Safety of [225Ac]Ac-PSMA-617 Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Highly Advanced mCRPC with Poor Prognosis

et al. 2021

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“…A second Indian study from Chandigarh has also shown the impact of 225 Ac-PSMA-617 on the health-related quality of life of 11 patients who had failed treatment with two or more lines of approved agents for mCRPC [ 78 ]. After a median of 2 cycles of 225 Ac-PSMA-617, 46% of patients achieved a PSA decline of 50% or more.…”

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

confidence: 99%

“…Among the four domains evaluated by the questionnaire, significant improvement occurred in the physical and emotional wellbeing domains. The physical symptoms that showed improvement with 225 Ac-PSMA-617 therapy were pain, difficulty with urination, fatigue, and restriction in physical activity [ 78 ]. The positive impact of 225 Ac-PSMA-617 on patients’ quality of life was also demonstrated in a report from Nijmegen, the Netherlands, of Dutch patients treated at Heidelberg, Germany, with 225 Ac-PSMA-617 for mCRPC [ 79 ].…”

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

Vorster

et al. 2021

Eur J Nucl Med Mol Imaging

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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.

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“…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 1–3 . 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.…”

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confidence: 99%

Delayed Nephrotoxicity After 225Ac-PSMA-617 Radioligand Therapy

Satapathy

Sharma²,

Sood

et al. 2022

Clin Nucl Med

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177 Lu-PSMA-617 radioligand therapy (RLT) has evolved as a suitable alternative to existing therapeutic options in patients with metastatic castration-resistant prostate cancer. With the emergence of α-emitters such as 225 Ac, the efficacy of PSMA-RLT has further improved. Xerostomia and myelosuppression are common early treatment-emergent adverse events in patients receiving this therapy; however, data on long-term toxicity are relatively scarce. In this report, we describe a 76-year-old man with metastatic castration-resistant prostate cancer, who after having an initial excellent response to 2 cycles of 225 Ac-PSMA-617 RLT, developed delayed nephrotoxicity in the form of tubulointerstitial nephritis.

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Health-related quality-of-life outcomes with actinium-225-prostate-specific membrane antigen-617 therapy in patients with heavily pretreated metastatic castration-resistant prostate cancer

Cited by 21 publications

References 19 publications

Efficacy and Safety of [225Ac]Ac-PSMA-617 Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Highly Advanced mCRPC with Poor Prognosis

Efficacy and Safety of [225Ac]Ac-PSMA-617 Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Highly Advanced mCRPC with Poor Prognosis

Global experience with PSMA-based alpha therapy in prostate cancer

Delayed Nephrotoxicity After 225Ac-PSMA-617 Radioligand Therapy

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