BACKGROUND : A remarkable therapeutic efficacy has been demonstrated with 225Ac-prostate-specific membrane antigen (PSMA)-
617 in heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients.We report our experience with 225Ac-
PSMA-617 therapy in chemotherapy-naïve patients with advanced metastatic prostate carcinoma.
METHODS : Seventeen patients with advanced prostate cancer were selected for treatment with 225Ac-PSMA-617 in 2-month
intervals, with initial activity of 8 MBq, then de-escalation to 7 MBq, 6 MBq or 4 MBq in cases of good response. In one
patient, activity was escalated to 13 MBq in the third cycle. Fourteen patients had three treatment cycles administered, while in
three patients treatment was discontinued after two cycles due to good response. Six out of 17 patients received additional
treatments after the third cycle. Prostate-specific antigen (PSA) was measured every 4 weeks for PSA response assessment. 68Ga-
PSMA-PET/CT was used for functional response assessment before each subsequent treatment cycle. Serial full blood count,
renal function test, and liver function were obtained to determine treatment-related side effects.
RESULTS : Good antitumor activity assessed by serum PSA level and 68Ga-PSMA-PET/CT was seen in 16/17 patients. In 14/17
patients, PSA decline ≥90% was seen after treatment, including seven patients with undetectable serum PSA following two (2/7)
or three cycles (5/7) cycles of 225Ac-PSMA-617. Fifteen of 17 patients had a > 50% decline in lesions avidity for tracer on 68Ga-
PSMA-PET/CT including 11 patients with complete resolution (PET-negative and either stable sclerosis on CT for bone or
resolution of lymph node metastases) of all metastatic lesions. Grade 1/2 xerostomia was seen in all patients, and none was severe
enough to lead to discontinuation of treatment. One patient had with extensive bone marrow metastases and a background anemia
developed a grade 3 anemia while another patient with solitary kidney and pre-treatment grade 3 renal failure developed grade 4
renal toxicity following treatment. The group presented with significant palliation of bone pain and reduced toxicity to salivary
glands due to de-escalation.
CONCLUSIONS : 225Ac-PSMA-617 RLTof chemotherapy-naïve patients with advanced metastatic prostate carcinoma led to a ≥ 90% decline in serum PSA in 82% of patients including 41% of patients with undetectable serum PSA who remained in remission
12 months after therapy. The remarkable therapeutic efficacy reported in this study could be achieved with reduced toxicity to
salivary glands due to de-escalation of administered activities in subsequent treatment cycles. This necessitates further exploration
for informing clinical practice and clinical trial design.
Hayes, Vanessa M.; Bornman, Maria S. (Riana)(American Society of Clinical Oncology, 2017-03-21)
Prostate cancer (PCa) is the most common cancer
diagnosis in men from economically stable countries
and is a leading cause of cancer-related
death.1 However, the population with the highest
reported incidence and ...
Sathekge, Mike Machaba; Lengana, Thabo; Maes, Alex; Vorster, Mariza; Zeevaart, Jan Rijn; Lawal, Ismaheel; Ebenhan, Thomas; Van de Wiele, Christophe(Springer, 2018-02)
PURPOSE : The incidence of prostate cancer is 60% higher and
the mortality rate is two- to three-times greater in black versus
white men. We report on differences in 68Ga-PSMA-11 PET/CT imaging findings in 77 black ...
Adam, Ahmed; Engelbrecht, Matthys J.; Bornman, Maria S. (Riana); Manda, S.O.M. (Samuel); Moshokoa, Evelyn M.; Feilat, Rasmi A.(Wiley-Blackwell, 2011-04)
• To evaluate the investigational role, ideal
threshold and indications of the Prostate
CAncer gene 3 (PCA3) assay in a South
• To better define the universality of the
above marker since ...