PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with <sup>177</sup>Lu-Labeled PSMA-617

Kratochwil, Clemens; Giesel, Frederik L.; Stefanova, M.; Benešová, Martina; Bronzel, Marcus; Afshar‐Oromieh, Ali; Mier, Walter; Eder, Matthias; Kopka, Klaus; Haberkorn, Uwe

doi:10.2967/jnumed.115.171397

Cited by 489 publications

(471 citation statements)

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“…Those men with progressive disease who do not respond to 177 Lu PSMA therapy range from 10% to 32%. One of the larger studies, with 56 men enrolled, had 80% of all men enrolled had a PSA response to therapy3 All currently published studies with 177 Lu PSMA therapy in prostate cancer are retrospective, mostly single arm, and involve a variety of treatment regimens, both in terms of dose given (ranging from 3.5 to 8.0 Gbq/injection of Lu PSMA) and the number of doses administered (ranges from a single injection up to 4–6 injections 6 weeks apart) 2, 3, 4, 5, 6, 8, 9, 27, 39. This makes interpretation of the efficacy of the treatment difficult at this stage.…”

Section: Treatment Efficacymentioning

confidence: 99%

Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Emmett

Willowson

Violet

et al. 2017

J of Medical Radiation Sci

235

233

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Prostate‐specific membrane antigen (PSMA) is a receptor on the surface of prostate cancer cells that is revolutionising the way we image and treat men with prostate cancer. New small molecule peptides with high‐binding affinity for the PSMA receptor have allowed high quality, highly specific PET imaging, in addition to the development of targeted radionuclide therapy for men with prostate cancer. This targeted therapy for prostate cancer has, to date, predominately used Lutetium 177 (Lu) labelled PSMA peptides. Early clinical studies evaluating the safety and efficacy of Lu PSMA therapy have demonstrated promising results with a significant proportion of men with metastatic prostate cancer, who have already failed other therapies, responding clinically to Lu PSMA. This review discusses the practical issues of administering Lu PSMA, and gives an overview of the findings from currently published trials in regards to treatment response rates, expected toxicities and safety.

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Section: Treatment Efficacymentioning

confidence: 99%

Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Emmett

Willowson

Violet

et al. 2017

J of Medical Radiation Sci

235

233

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“…(8,12). Nevertheless, tolerance limits for normal organs reported in the literature are based on external beam radiotherapy and have only been extrapolated to RLT using radiobiological models, which themselves have manifold limitations as reviewed recently (13).…”

Section: Abstract Current Treatment Protocols For 177mentioning

confidence: 99%

“…Based on the available dosimetry data, the 177 Lu-PSMA-617 activities used for the first PSMA-RLTs have been chosen cautiously. However, even these very first reports demonstrated promising anti-tumor activity (8,12). Nevertheless, tolerance limits for normal organs reported in the literature are based on external beam radiotherapy and have only been extrapolated to RLT using radiobiological models, which themselves have manifold limitations as reviewed recently (13).…”

Section: Introductionmentioning

confidence: 99%

“…Coupling with DOTA enables labeling with several diagnostic and therapeutic radionuclides (5). Different centers (6)(7)(8) reported favorable dosimetry for 177 Lu-PSMA-617, which in regard to kidney (approx. 0.6 Gy/GBq) and red marrow dose (approx.…”

Section: Introductionmentioning

confidence: 99%

“…If toxicities were comparable to the placebo group of the ALSYMPCA-trial (14), individual dose escalations for non-responders were considered ethically justified, resulting in a short learning-phase using heterogeneous dosing regimens between respective dose escalation groups. Data of these heterogeneous interim patients were not suitable for this kind of systematical evaluation, nevertheless some have been made public available within other publications (8,15). The chronology how this dose escalation was embedded into clinical practice is summarized in Fig.…”

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confidence: 99%

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Repeated ¹⁷⁷Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

et al. 2017

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Current treatment protocols for 177Lu-PSMA-617 therapies were cautiously derived from dosimetry data, but their practical appropriateness have not yet been proven clinically.We retrospectively report our clinical observations using four different treatment activities. Methods: Forty patients with advanced prostate cancer and positive uptake in PSMA-imaging were treated in fractions of 4 GBq / 80 nmol, 6 GBq / 120 nmol, 7.4 GBq / 150 nmol or 9.3 GBq / 150 nmol 177 Lu-activity / precursor-amount (n=10, respectively) every 2 months. Safety lab was checked every 2 weeks, PSA-response every 4 weeks; other effects were assessed per anamnesis. Results: Initial PSA response presented no correlation to treatment activity. However, 2/10, 4/10, 4/10 and 7/10 patients with doses of 4, 6, 7.4 and 9.3 GBq were in partial remission 8 weeks after completing all 3 cycles;This would be in line with, but due to low patient numbers not proving, a positive doseresponse-relationship. Acute hematological toxicity was also irrespective of treatment activity and no more than one grade-3/4 toxicity was observed in each group.Nevertheless, in contrast to the other groups the mean platelet count in the 9. (8,12). Nevertheless, tolerance limits for normal organs reported in the literature are based on external beam radiotherapy and have only been extrapolated to RLT using radiobiological models, which themselves have manifold limitations as reviewed recently (13). Thus, dosimetry in nuclear medicine can only approximate a guidance level for dosing RLT but the optimal treatment regime has still to be refined clinically.In this retrospective analysis we report our clinical experience with fractions of 4 GBq, 6GBq, 7.4 GBq or 9.3 GBq 177 Lu-PSMA-617 repeated every 2 months.by on May 10, 2018. For personal use only. jnm.snmjournals.org Downloaded from MATERIALS AND METHODS Patients 177Lu-PSMA-RLT was performed under the conditions of the updated declaration of Helsinki, § 37 (Unproven interventions in clinical practice) and in accordance to the German Pharmaceuticals Law §13(2b) as a salvage therapy for patients with mCRPC, which had to be resistant against or ineligible for approved options and presented with progressive disease. Patient selection is outlined in Fig. 1. For patients stratified to 177 Lu-PSMA-617, each dose level was administered to 10 consecutive patients. If toxicities were comparable to the placebo group of the ALSYMPCA-trial (14), individual dose escalations for non-responders were considered ethically justified, resulting in a short learning-phase using heterogeneous dosing regimens between respective dose escalation groups. Data of these heterogeneous interim patients were not suitable for this kind of systematical evaluation, nevertheless some have been made public available within other publications (8,15). The chronology how this dose escalation was embedded into clinical practice is summarized in Fig. 2. Patient characteristics were summarized in (Table 1). All patients were informed about the experime...

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Imaging Locally Advanced, Recurrent, and Metastatic Prostate Cancer

et al. 2017

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PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with ¹⁷⁷Lu-Labeled PSMA-617

Cited by 489 publications

References 28 publications

Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Repeated ¹⁷⁷Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

Imaging Locally Advanced, Recurrent, and Metastatic Prostate Cancer

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PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617

Cited by 489 publications

References 28 publications

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Repeated 177Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

Imaging Locally Advanced, Recurrent, and Metastatic Prostate Cancer

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Product

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PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with ¹⁷⁷Lu-Labeled PSMA-617

Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Repeated ¹⁷⁷Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq