Efficacy and safety of 225Ac-PSMA-617 targeted alpha therapy in metastatic castration-resistant Prostate Cancer patients
Conclusion: 225Ac-PSMA-617 TAT showed promising disease control rate, even when all other therapeutic options were exhausted, with low treatment-related toxicities.
CONCLUSION: The results indicate that after administration of [18F]DCFPyL the amount of radioactivity in the saliva increased over 120 min in all the patients (5/5). Moreover, radioactivity in the saliva was also observed on the PET images. This finding helps expand our knowledge about the fate of PSMA-targeted agents in the salivary glands and may help researchers design more-effective strategies to prevent xerostomia. However, it will be interesting to identify if the radioactivity in the saliva is contributed by intact [18F]DCPyL or its metabolite. We intend to characterize the radioactive content in the saliva in the future studies.
Conclusions: These studies establish that salivary gland and kidney uptake can be drastically reduced without affecting tumor uptake of 177Lu-PSMA617 simply by reducing its specific activity. These studies provide proof of concept solutions for xerostomia and renal toxicity arising from [177Lu]-PSMA617. References: Pillarsetty N, et al. J Nucl Med 2016 vol. 57 (supplement_2), 528.
The objective of this study is to evaluate the safety and therapeutic efficacy of 225Ac-PSMA-617 targeted alpha therapy (TAT) in metastatic castration resistant prostate cancer patients (mCRPC). Methods: The study has been approved by the Institute Ethics Committee (IEC:518). 28 mCRPC patients refractory to therapy options including first and second generation anti-androgen therapies, taxane-based chemotherapies, and 177Lu-PSMA-617 therapy were treated with 225Ac-PSMA-617 TAT (100 KBq/Kg body weight) at an interval of 8 weeks up to 7 cycles. The patients were treated from April 2018 to November 2019 with median follow-up d...
Conclusions: In this small cohort Ac-225-PSMA I&T RLT showed antitumor effect in end stage mCRPC even after failure of Lu-177 PSMA-ligand therapy in more than 40%. Grade 3/4 hematological side effects in 50% of patients and Grade 1-2 xerostomia in 11/12 patients indicate moderate tolerability in this heavily pretreated end stage patient group. These results are comparable to data for Ac225 PSMA-617 after failure of Lu-177 therapy.
Conclusions: 225Ac-PSMA-617 is a safe and tolerable treatment option for mCRPC that demonstrates marked anti-tumor activity with improvement in quality of life even in patients of metastatic CRPC who have been previously treated with taxane based chemotherapy. Significant improvement in survival and quality of life be achieved even in patients with residual disease which otherwise have very limited options. Further studies in clinical trial settings are essential for further assessing the effects of this very encouraging modality.
Conclusions: Long progression free survival times and the absence of serious adverse events in this patient group encourage further evaluation of extended radioligand therapy in patients with advanced disease. Figure: 68Ga-PSMA PET/CT images of a patient undergoing extended therapy with 10 cycles during 30 months until progression.
AbstractIntroductionA new therapeutic option for metastatic castration –resistant prostate cancer (mCRPC) of heavily pre-treated patients lies in177Lu-PSMA-617 radioligand therapy.MethodsOn the basis of PSMA-targeted68Ga-PSMA-11 PET/CT, 32 consecutive mCRPC patients were selected for177Lu-PSMA-617 therapy (6 GBq/cycle, 2 to 6 cycles, 6 –10 weeks apart) and followed until death. Post-therapy whole-body (WB) dosimetry and68Ga-PSMA-11 PET/CT data were compared and related to progression free and overall survival.Results177Lu-PSMA-617 dosimetry after the first cycle indicated high tumor doses for skeletal (4.01 &pl...
Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with 225Ac-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after 225Ac-PSMA-617 treatment. Methods: 225Ac-PSMA-617 was administered to patients who had metastatic castration-resistant prostate carcinoma and who had exhausted available therapy options for their disease. Full blood count, glomerular...
ConclusionsOur results suggest that a single course of tandem therapy with low-activity225Ac-PSMA-617/full-activity177Lu-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.
Conclusion: A factor 3–4 lower treatment activity for 90Y-PSMA-617 translates into a comparable dosimetry estimate and clinical findings similar to those of 177Lu-PSMA-617. However, safety was demonstrated only for patients with oligometastatic disease. Further studies are needed to evaluate its potential in patients with more disseminated bone involvement or visceral metastasis.