A Pilot Safety Study of Increased Activities (Doses) of ²²⁵Ac-PSMA for the Treatment of Metastatic Castration-Resistant Prostate Cancer

Abstract

Introduction: 225Ac-PSMA is a promising drug for radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). Despite the large number of studies in this area, the optimal therapeutic activity of the drug is a debatable issue. The purpose of this study is to evaluate the safety of a single dose of 225Ac-PSMA at a fixed dosage (regardless of patient weight) of 6, 9 and 12 MBq.Material and methods: The study included 9 patients, 3 in each group, with mCRPC progressing against the background of standard treatment (from 1 to 6 lines of mCRPC therapy in history). The observation period was 5 weeks, instrumental, laboratory and clinical indicators were used to assess safety. 225As-PSMA was manufactured directly in the clinic in accordance with the order of the Ministry of Health of Russia 1218n dated 11/12/2020.Results: During the observation period, one patient from the group with the lowest administered activity had a serious adverse event (hospitalization due to pneumonia). When discussing this case, it was concluded that there was no connection with the drug, since pneumonia in this patient was not accompanied by leukopenia or neutropenia. All patients experienced dry mouth. In patients who received 9 and 12 MBq a decrease in the salivary gland function was recorded by scintigraphy. In two patients, severe weakness was revealed, in one of them the weakness could be associated with pneumonia, in the other patient, the weakness was most likely caused by the therapy. No cases of nephrotoxicity were recorded. Hematological toxicity was temporary reversible; no additional treatment was required in any of the cases. The most common adverse event: leukopenia, neutropenia (78 % of patients), grade III leukopenia was observed in two (22 %) patients, grade III neutropenia in one (11 %) patient.Conclusions: A single administration of 225Ac-PSMA in the studied range of activities was safe, dose-limiting toxicity was not achieved.