Dose escalation experience with Ac-225-PSMA-617 in PSMA targeting alpha-radiation therapy of patients with mCRPC

Aim: To develop a standard treatment protocol for Ac-225-PSMA-617 PSMA targeting alpha-radiation therapy. Methods: Treatment dose in kBq per kg body-weight (kBq/kgBW) was stepwise increased from 50 kBq/kg (n=2), 100kBq/kgBW (n=2), 150kBq/kgBW (n=2) and 200 kBq/kgBW (n=4). Additionally, a 2-monthly fractionation regime was compared with a 4-monthly administration interval (n=4). Hematological toxicity, clinical exam and patient self-reported side-effects were assessed every 4 weeks, in case of irregular findings every 2 weeks. In addition PSA was also checked every 4 weeks. Results: Severe xerostomia was dose-limiting before hematological toxicity became relevant. 3 patients with 200kBq/kg and 1 patient with 150kBq/kg requested dose reduction. Thus 100kBq/kgBW was defined as standard treatment dose per cycle. 2/4 patients with a 4-monthly treatment interval had PSA-progression before the succeeding cycle, which then also demonstrated also to be less effective than the 2nd cycle during the 2-monthly treatment regime. With doses above or equal to 100 kBq/kgBW per cycle tumor response in regard to a PSA-decline of >50% was demonstrated in about 70% of the treated patients. Conclusions: A standard treatment dose of 100kBq/kgBW administered every two month seems both associated with remarkable anti-tumor activity and tolerability. In our hospital it became the standard treatment activity for the first phase of routinely clinical application as a salvage therapy for mCRPC.

KRATOCHWIL Clemens;  BRUCHERTSEIFER Frank;  GIESEL Frederik;  APOSTOLIDIS Christos;  HABERKORN Uwe;  MORGENSTERN Alfred; 

2016-11-22

SPRINGER

JRC101407

1619-7070,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC101407,   

10.1007/s00259-016-3484-4,