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Advances in Targeted Alpha Therapy for Prostate Cancer.
Ann Oncol 2019AO

Abstract

BACKGROUND

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.

DESIGN

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.

RESULTS

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 (AR)-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.

CONCLUSIONS

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.

Authors+Show Affiliations

Department of Radiological Sciences, Oncology and Anatomo-Pathology, Sapienza, University of Rome, Rome, Italy.Department of Medical Oncology, Radboud UMC, Nijmegen, the Netherlands.Department of Urology, Technical University of Munich, Rechts der Isar Medical Center, Munich, Germany.Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.Department of Imaging Sciences and Biomedical Engineering, King's College, London, UK.Center for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland Cancer Center, Belfast City Hospital, Belfast, Northern Ireland.Department of Urology, Keio University School of Medicine, Tokyo, Japan.Medical Physics Department, "Policlinico Umberto I" University Hospital, Rome, Italy.The Royal Marsden Hospital, Sutton, UK.Carolina Urologic Research Center, Myrtle Beach, South Carolina, USA.Tulane Cancer Center, Tulane University, New Orleans, Louisiana, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31418764

Citation

De Vincentis, G, et al. "Advances in Targeted Alpha Therapy for Prostate Cancer." Annals of Oncology : Official Journal of the European Society for Medical Oncology, 2019.
De Vincentis G, Gerritsen W, Gschwend JE, et al. Advances in Targeted Alpha Therapy for Prostate Cancer. Ann Oncol. 2019.
De Vincentis, G., Gerritsen, W., Gschwend, J. E., Hacker, M., Lewington, V., O'Sullivan, J. M., ... Sartor, O. (2019). Advances in Targeted Alpha Therapy for Prostate Cancer. Annals of Oncology : Official Journal of the European Society for Medical Oncology, doi:10.1093/annonc/mdz270.
De Vincentis G, et al. Advances in Targeted Alpha Therapy for Prostate Cancer. Ann Oncol. 2019 Aug 16; PubMed PMID: 31418764.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Advances in Targeted Alpha Therapy for Prostate Cancer. AU - De Vincentis,G, AU - Gerritsen,W, AU - Gschwend,J E, AU - Hacker,M, AU - Lewington,V, AU - O'Sullivan,J M, AU - Oya,M, AU - Pacilio,M, AU - Parker,C, AU - Shore,N, AU - Sartor,O, Y1 - 2019/08/16/ PY - 2019/8/17/entrez KW - Targeted alpha therapy (TαT) KW - prostate cancer KW - prostate-specific membrane antigen (PSMA) KW - radium-223 JF - Annals of oncology : official journal of the European Society for Medical Oncology JO - Ann. Oncol. N2 - BACKGROUND: 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. DESIGN: 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. RESULTS: 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 (AR)-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. CONCLUSIONS: 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. SN - 1569-8041 UR - https://www.unboundmedicine.com/medline/citation/31418764/Advances_in_Targeted_Alpha_Therapy_for_Prostate_Cancer L2 - https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdz270 DB - PRIME DP - Unbound Medicine ER -