Advances in targeted alpha therapy for prostate cancer.
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Date
2019-11ICR Author
Author
De Vincentis, G
Gerritsen, W
Gschwend, JE
Hacker, M
Lewington, V
O'Sullivan, JM
Oya, M
Pacilio, M
Parker, C
Shore, N
Sartor, O
Targeted Alpha Therapy Prostate Working Group
Type
Journal Article
Metadata
Show full item recordAbstract
Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment.
Collections
Subject
Targeted Alpha Therapy Prostate Working Group
Humans
Prostatic Neoplasms
Heterocyclic Compounds, 1-Ring
Prostate-Specific Antigen
Dipeptides
Radiopharmaceuticals
Radioimmunotherapy
Radiotherapy Planning, Computer-Assisted
Alpha Particles
Male
Clinical Trials, Phase III as Topic
Tumor Microenvironment
Precision Medicine
Progression-Free Survival
Language
eng
License start date
2019-11
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 2019, 30 (11), pp. 1728 - 1739
Except where otherwise noted, this item's license is described
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https://creativecommons.org/licenses/by/4.0
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