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Titel: 225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer : pilot experience
VerfasserIn: Khreish, Fadi
Ebert, Niklas
Ries, Martin
Maus, Stephan
Rosar, Florian
Bohnenberger, Hendrik
Stemler, Tobias
Saar, Matthias
Bartholomä, Mark
Ezziddin, Samer
Sprache: Englisch
Titel: European Journal of Nuclear Medicine and Molecular Imaging
Bandnummer: 47 (2020)
Heft: 3
Seiten: 721-728
Verlag/Plattform: Springer Nature
Erscheinungsjahr: 2019
Freie Schlagwörter: Metastatic castration-resistant prostate cancer
177Lu-PSMA-617 therapy
225Ac-PSMA-617 therapy
Tandem PSMA radioligand therapy
Combination PSMA radioligand therapy
Xerostomia
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Purpose Up to 30% of patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) never respond or develop resistance to 177Lu-labeled PSMA-targeted radioligand monotherapy. Single-agent PSMA-targeted radioligand therapy (PRLT) with the alpha-emitter 225Ac showed promise against mCRPC but may cause severe and/or persistent xerostomia, which may substantially impair patients’ quality-of-life. We hypothesized that when 177Lu-PSMA ligand alone is ineffective, tandem therapy with low-activity 225Ac-PSMA ligand plus full activity of the beta emitter may enhance efficacy while minimizing xerostomia severity. Methods We retrospectively analyzed pilot experience with 1 course of 225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy in our first 20 patients with mCRPC receiving this intervention after insufficiently responding to 177Lu-PSMA-617 monotherapy. This cohort had late-stage/end-stage disease with high baseline prostate-specific antigen (PSA) concentration (median 215 ng/mL), heavy pre-treatment (abiraterone and/or enzalutamide, and 177Lu-PRLT [median cumulative activity, 26.3 GBq] in 20/20 patients, 100%; docetaxel and/or cabazitaxel in 13/20 patients, 65%), and frequent Eastern Cooperative Oncology Group performance status of 2 (8/20 patients, 40%). Results Median (minimum–maximum) administered activities were 225Ac-PSMA-617, 5.3 (1.5–7.9) MBq, and 177Lu-PSMA-617, 6.9 (5.0–11.6) GBq. Significant responders to tandem therapy received 177Lu-PSMA-617 monotherapy as maintenance (median [minimum–maximum]: 1 [0–5] cycle). After a median (minimum–maximum) 22 (14–63) weeks’ follow-up, 13/20 patients (65%) had as best biochemical response a PSA decline > 50%. Median (95% confidence interval) progression-free survival was 19 (12–26) weeks, and overall survival was 48 (4–92) weeks post-tandem therapy administration. Xerostomia was reported as grade 1 (very mild) in 8/20 patients (40%), grade 2 (mild) in 5/20 (25%), and grade 3/4 in 0/20. Conclusions Our results suggest that a single course of tandem therapy with low-activity 225Ac-PSMA-617/full-activity 177Lu-PSMA-617 may safely enhance response to PRLT in men with late-stage/end-stage mCRPC while minimizing xerostomia severity. Formal study of this combination is warranted.
DOI der Erstveröffentlichung: 10.1007/s00259-019-04612-0
URL der Erstveröffentlichung: https://link.springer.com/article/10.1007/s00259-019-04612-0
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-377310
hdl:20.500.11880/34121
http://dx.doi.org/10.22028/D291-37731
ISSN: 1619-7089
1619-7070
Datum des Eintrags: 26-Okt-2022
Bezeichnung des in Beziehung stehenden Objekts: Electronic supplementary material
In Beziehung stehendes Objekt: https://static-content.springer.com/esm/art%3A10.1007%2Fs00259-019-04612-0/MediaObjects/259_2019_4612_MOESM1_ESM.docx
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Radiologie
M - Urologie und Kinderurologie
Professur: M - Prof. Dr. Samer Ezziddin
M - Prof. Dr. Michael Stöckle
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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