Pilot Study of Hyperfractionated Dosing of Lutetium-177–Labeled Antiprostate-Specific Membrane Antigen Monoclonal Antibody J591 ( 177 Lu-J591) for Metastatic Castration-Resistant Prostate Cancer

[摘要] Background. Phase I and II single-dose studies of lutetium177 (177Lu)-J591, a radio-labeled antibody binding prostatespecific membrane antigen (PSMA), demonstrated safety and efficacy with dose response. Modest dose fractionation of 177Lu-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 castrationresistant prostate cancer and adequate organ function were enrolled. 177Lu-J591 was administered at 25 mCi/m2 every 2 weeks until the emergence of related grade 2 toxicity. 177Lu-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/m2 ). 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 177Lu-J591 is feasible but does not seem to have significant advantages over the twodose fractionation regimen.

[学科分类] 地质学