title: Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  To assess the efficacy of a single infusion of radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (lutetium-177; (177)Lu) by prostate-specific antigen (PSA) decline, measurable disease response, and survival.
  
  
  METHODS
  In this dual-center phase II study, two cohorts with progressive metastatic castration-resistant prostate cancer received one dose of (177)Lu-J591 (15 patients at 65 mCi/m(2), 17 at 70 mCi/m(2)) with radionuclide imaging. Expansion cohort (n = 15) received 70 mCi/m(2) to verify response rate and examine biomarkers.
  
  
  RESULTS
  Forty-seven patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received (177)Lu-J591. A total of 10.6% experienced ≥50% decline in PSA, 36.2% experienced ≥30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity, with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. A total of 25.5% experienced grade 4 neutropenia, with one episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m(2)) resulted in more 30% PSA declines (46.9% vs. 13.3%, P = 0.048) and longer survival (21.8 vs. 11.9 months, P = 0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious nonhematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond.
  
  
  CONCLUSIONS
  A single dose of (177)Lu-J591 was well tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose response. Imaging biomarkers seem promising.
authors.affiliation: Authors' Affiliations: Weill Cornell Medical College (WCMC); Weill Cornell Cancer Center; Memorial Sloan-Kettering Cancer Center (MSKCC), New York, New York; and University of North Carolina Chapel Hill, North Carolina.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Tagawa
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Milowsky
authors.forename: Michael
authors.initials: M
authors.lastname: Morris
authors.forename: Shankar
authors.initials: S
authors.lastname: Vallabhajosula
authors.forename: Paul
authors.initials: P
authors.lastname: Christos
authors.forename: Naveed H
authors.initials: NH
authors.lastname: Akhtar
authors.forename: Joseph
authors.initials: J
authors.lastname: Osborne
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Goldsmith
authors.forename: Steve
authors.initials: S
authors.lastname: Larson
authors.forename: Neeta Pandit
authors.initials: NP
authors.lastname: Taskar
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
authors.forename: David M
authors.initials: DM
authors.lastname: Nanus
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000276:immunology*; D005500:Follow-Up Studies; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors / Q000276:immunology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; C478680:J591 monoclonal antibody; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen