Intermittent Radioligand Therapy with 177 Lu-PSMA-617 for Oligometastatic Castration-Resistant Prostate Cancer.
In: Cancers, Jg. 15 (2023-09-15), Heft 18, S. 4605-4615
Online
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Zugriff:
Simple Summary: Radioligand therapy (RLT) usually consists of predefined cycles of 177Lu-PSMA-617 every 6–8 weeks. Although side-effects of RLT are considered well tolerable, cumulative absorbed doses in kidneys and an increased probability of chronic renal failure in responders remain concerns. The aim of our retrospective study, therefore, was to assess the efficacy and safety of intermittent, response-adapted RLT with 177Lu-PSMA-617 in oligometastatic mCRPC patients. Intermittent RLT with 177Lu-PSMA-617 is effective and can result in long-lasting disease control in selected patients even when including multiple treatment-free periods. 177Lu-PSMA-617 radioligand therapy (177Lu-PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC) currently consists of 4–6 cycles of 6.0–7.4 GBq of 177Lu-PSMA-617 each every 6–8 weeks. While safety and efficacy could be demonstrated in larger prospective trials irrespective of the tumor burden at 177Lu-PSMA RLT initiation, increased renal absorbed doses due to a reduced tumor sink effect in early responding, oligometastatic mCRPC patients pose difficulties. Response-adapted, dose distributing, intermittent treatment with up to six cycles has not been routinely performed, due to concerns about the potential loss of disease control. Treatment was discontinued in 19 early-responding patients with oligometastatic tumor burden after two (IQR 2–3) cycles of 177Lu-PSMA-RLT and 6.5 ± 0.7 GBq per cycle and resumed upon 68Ga-PSMA-11-PET/CT-based progression (according to the PCWG3 criteria). Subsequent treatment breaks were imposed if a PSMA-based imaging response could be achieved. A total of five (IQR 3–6) cycles reaching a cumulative activity of 32 ± 11 GBq were applied. A routine blood work-up including blood counts and liver and renal function was measured throughout the 177Lu-PSMA-RLT and follow-up to grade toxicity according to CTCAE v5.0 criteria. Survival outcome was calculated based on the Kaplan–Meier method. In total, treatment-free periods of 9 (IQR 6–17) cumulative months and the application of 177Lu-PSMA-RLT cycles over 16 (IQR 9–22) months could be achieved. Fifteen (84%) patients responded to subsequent cycles after the first treatment break and in 7/19 (37%) patients, intermittent 177Lu-PSMA-RLT consisted of ≥2 treatment breaks. The median PFS was 27 months (95% CI: 23–31) and overall survival was 45 months (95% CI: 28–62). No grade ≥3 hematological or renal toxicities could be observed during the 45 ± 21 months of follow-up. The cumulative mean renal absorbed dose was 16.7 ± 8.3 Gy and 0.53 ± 0.21 Gy/GBq. Intermittent radioligand therapy with 177Lu-PSMA-617 is feasible in early-responding patients with oligometastatic disease. A late onset of progression after subsequent cycles and the absence of significant toxicity warrants further investigation of the concept of intermittent treatment in selected patients. [ABSTRACT FROM AUTHOR]
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Intermittent Radioligand Therapy with 177 Lu-PSMA-617 for Oligometastatic Castration-Resistant Prostate Cancer.
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Autor/in / Beteiligte Person: | Mader, Nicolai ; Schoeler, Christina ; Pezeshkpour, Niloufar ; Klimek, Konrad ; Groener, Daniel ; Happel, Christian ; Tselis, Nikolaos ; Mandel, Philipp ; Grünwald, Frank ; Sabet, Amir |
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Zeitschrift: | Cancers, Jg. 15 (2023-09-15), Heft 18, S. 4605-4615 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 2072-6694 (print) |
DOI: | 10.3390/cancers15184605 |
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