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Outcome and safety of single-dose docetaxel–augmented targeted radionuclide therapy using [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy in treatment-refractory mCRPC: preliminary evidence from a pilot experience

Year: 2026

Type: article

Abstract: BACKGROUND: the aim of this study is to investigate the safety profile and efficacy of single-dose docetaxel augmented targeted radionuclide therapy (TRT) in the form of prostate-specific membrane antigen (PSMA)- targeted radioligand therapy (RLT) using Lutetium-177 (177Lu) in patients who have progressed on PSMA-617 RLT. A retrospective analysis was conducted on 10 mCRPC patients (median age: 68 years; range: 51–74 years) who were progressing on prior RLT. The patients received one cycle of treatment involving 50 mg/m² of docetaxel combined with [177Lu]Lu-PSMA-617. Efficacy was assessed via biochemical (PSA, PCWG3) and molecular imaging endpoints (TLP/MTV via [68Ga]Ga-PSMA-11 PET/CT). PSA-progression-free survival (PSA-PFS) and overall survival (OS) were analyzed using Kaplan–Meier statistics. Toxicity was graded by CTCAE v5.0. RESULTS: After single-dose docetaxel augmented [177Lu]Lu-PSMA-617 RLT, 60% of the patients showed a disease stabilization for 4–8 weeks based on PSA (10% partial remission and 50% stable disease). Based on the molecular imaging-based response assessment, 62.5% of the patients showed a disease stabilization (25% parietal response and 37.5% stable disease). The median PSA-PFS and OS thereafter were 4.4 months (95%CI: 1.3–7.6 months) and 7.2 months (95%CI: 2.9–11.5 months), respectively. The augmentation therapy was well-tolerated without any serious acute adverse events. During the first 4–8 weeks thereafter 3 patients exhibited transient grade 3 anemia and one patient a transient grade 2 nephrotoxicity. CONCLUSIONS: This pilot experience demonstrates that single-dose docetaxel application to [177Lu]Lu-PSMA-617 radioligand therapy is feasible and may present an option for late-stage heavily pretreated mCRPC progressing on PSMA-617 RLT. Formal study of this combination is warranted.

Source: EJNMMI Research

DOI: 10.1186/s13550-026-01408-w