Abstract
LESSONS LEARNED: Hyperfractionation of lutetium-177 ((177) Lu)-J591 for patients with metastatic castration-resistant prostate cancer did not appear to have any additional advantage over the single dose (177) Lu-J591 or fractionated two-dose (177) Lu-J591 therapy. Definite conclusions were challenging because of the small sample size of this study, and so further studies are needed to evaluate the viability of the hypothesis. On the basis of available data, a registration study of (177) Lu-J591 (also known as TLX591) is planned and will use the two-dose fractionation schedule (Telix Pharma Q3 2019 update https://telixpharma.com/news-media/). BACKGROUND: Phase I and II single-dose studies of lutetium-177 ((177) Lu)-J591, a radio-labeled antibody binding prostate-specific membrane antigen (PSMA), demonstrated safety and efficacy with dose response. Modest dose fractionation of (177) Lu-J591 (2 doses) has less myelosuppression per similar cumulative dose, allowing higher doses to be administered safely. We hypothesized that additional dose fractionation would allow a higher cumulative dose, potentially with less toxicity and more efficacy. METHODS: Men with progressive metastatic castration-resistant prostate cancer and adequate organ function were enrolled. (177) Lu-J591 was administered at 25 mCi/m(2) every 2 weeks until the emergence of related grade 2 toxicity. (177) Lu-J591 imaging was performed and circulating tumor cell (CTC) counts were measured before and after treatment along with standard monitoring. RESULTS: Six subjects in a single cohort, with a median age of 68.6 years, were enrolled. Patients received three to six doses (cumulative 75-150 mCi/m(2) ). Two (33%) patients had >30% prostate-specific antigen (PSA) decline and three (50%) had CTC count decline. Two (33%) experienced grade (Gr) 4 neutropenia (without fever), three (50%) had Gr 4 thrombocytopenia (without hemorrhage), and two (33%) required platelet transfusions. Following hematological improvement, two patients developed worsening cytopenia during prostate cancer progression; bone marrow biopsies revealed infiltrative tumor replacing normal marrow elements without myelodysplasia. Targeting of known disease sites was seen on planar imaging in all. CONCLUSION: Hyperfractionation of (177) Lu-J591 is feasible but does not seem to have significant advantages over the two-dose fractionation regimen.