Abstract
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Objectives: 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.
Methods: The study has been approved by the Institute Ethics Committee (IEC:518). 10 metastatic castration resistant prostate cancers 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 3 cycles. The patients were treated from April 2018 to December 2018 with median follow-up duration was 6 months (range: 5 - 9 months). Hematologic, kidney, liver function tests and prostate specific antigen tests were repeated before and after every cycle of 225Ac-PSMA-617 TAT at 2, 4 and 8-week intervals. Treatment related side effects were assessed every 2 weeks on the basis of physical examination, vital signs, laboratory results (hematologic, kidney and liver function levels) and adverse events graded according the CTCAE v5.0. Response assessment included biochemical and molecular tumor response which were evaluated by the trend in PSA levels and follow-up 68Ga-PSMA PET/CT scan using PERCIST 1 criteria.
Results: All 10 patients included demonstrated extensive PSMA avid skeletal metastases on baseline 68Ga-PSMA PET/CT scan. The patients received a median of 2 cycles of 225Ac-PSMA-617 TAT. No patient experienced grade 3 or 4 hematologic or kidney toxicity. Regarding the liver function parameters, a significant decrease in the alkaline phosphatase values was observed in all the patients post-treatment (baseline: 1020 U/L, post-therapy: 276.5 U/L, P<0.0001). Grade 1 or 2 xerostomia was observed in 80% and Grade 2 anorexia in 30% of patients. Among the 10 patients, greater than 50% decline in PSA was observed in 9 patients and the remaining 1 patient demonstrated a >25% increase in PSA after the second cycle. According to PERCIST 1 criteria, 9/10 patients demonstrated partial response and 1 patient showed stable disease. No death was observed in the patient population and all the 90% of patients have shown sustained response till date.
Conclusions: Greater than 50% decline in PSA levels with synchronous reduction in the molecular tumor volume on 68Ga-PSMA PET/CT scan was exhibited 90% of the patients. None of the patients demonstrated grade 3 or 4 hematologic or kidney function toxicity and xerostomia. 225Ac-PSMA-671 TAT showed promising anti-tumor activity, sustained response and low treatment-related toxicities. Currently, at our department of Nuclear Medicine, the above promising results led to the commencement of an ongoing phase II clinical trial to validated the above findings.
