Repeated Lu-177-PSMA-617 radioligand therapy using treatment activities up to 9.3 GBq

Current treatment protocols for (177)Lu-PSMA-617 therapies were cautiously derived from dosimetry data, but their practical appropriateness have not yet been proven clinically. We retrospectively report our clinical observations using four different treatment activities. Methods: Forty patients with advanced prostate cancer and positive uptake in PSMA-imaging were treated in fractions of 4 GBq / 80 nmol, 6 GBq / 120 nmol, 7.4 GBq / 150 nmol or 9.3 GBq / 150 nmol (177)Lu-activity / precursor-amount (n = 10, respectively) every 2 months. Safety lab was checked every 2 weeks, PSA-response every 4 weeks; other effects were assessed per anamnesis. Results: Initial PSA response presented no correlation to treatment activity. However, 2/10, 4/10, 4/10 and 7/10 patients with doses of 4, 6, 7.4 and 9.3 GBq were in partial remission 8 weeks after completing all 3 cycles; This would be in line with, but due to low patient numbers not proving, a positive dose-response-relationship. Acute hematological toxicity was also irrespective of treatment activity and no more than one grade-3/4 toxicity was observed in each group. Nevertheless, in contrast to the other groups the mean platelet count in the 9.3 GBq group chronically decreased over time. Conclusion: If patients with diffuse red marrow infiltration and extensive chemotherapeutical pretreatments are excluded, treatment activities up to three injections of 9.3 GBq (177)Lu-PSMA-617 every two months are well tolerable. Further dose escalation should be conducted with care as the MTD seems to be close.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017 Aug 10 [Epub ahead of print]

Hendrik Rathke, Frederik L Giesel, Paul Flechsig, Klaus Kopka, Walter Mier, Markus Hohenfellner, Uwe Haberkorn, Clemens Kratochwil

University Hospital Heidelberg, Germany., German Cancer Research Center (dkfz), Germany.


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