title: Phase I trial of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for androgen-independent prostate cancer.
abstract: OBJECTIVE
  To determine the maximum-tolerated dose (MTD), toxicity, human antihuman antibody (HAHA) response, pharmacokinetics, organ dosimetry, targeting, and preliminary efficacy of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 ((90)Y-J591) in patients with androgen-independent prostate cancer (PC).
  
  
  METHODS
  Patients with androgen-independent PC and evidence of disease progression received indium-111-J591 for pharmacokinetic and biodistribution determinations followed 1 week later by (90)Y-J591 at five dose levels: 5, 10, 15, 17.5, and 20 mCi/m(2). Patients were eligible for up to three re-treatments if platelet and neutrophil recovery was satisfactory.
  
  
  RESULTS
  Twenty-nine patients with androgen-independent PC received (90)Y-J591, four of whom were re-treated. Dose limiting toxicity (DLT) was seen at 20 mCi/m(2), with two patients experiencing thrombocytopenia with non-life-threatening bleeding episodes requiring platelet transfusions. The 17.5-mCi/m(2) dose level was determined to be the MTD. No re-treated patients experienced DLT. Nonhematologic toxicity was not dose limiting. Targeting of known sites of bone and soft tissue metastases was seen in the majority of patients. No HAHA response was seen. Antitumor activity was seen, with two patients experiencing 85% and 70% declines in prostate-specific antigen (PSA) levels lasting 8 and 8.6 months, respectively, before returning to baseline. Both patients had objective measurable disease responses. An additional six patients (21%) experienced PSA stabilization.
  
  
  CONCLUSIONS
  The recommended dose for (90)Y-J591 is 17.5 mCi/m(2). Acceptable toxicity, excellent targeting of known sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation of (90)Y-J591 in the treatment of patients with PC.
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Milowsky
authors.forename: David M
authors.initials: DM
authors.lastname: Nanus
authors.forename: Lale
authors.initials: L
authors.lastname: Kostakoglu
authors.forename: Shankar
authors.initials: S
authors.lastname: Vallabhajosula
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Goldsmith
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000954:Antigens, Surface / Q000276:immunology*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D043425:Glutamate Carboxypeptidase II / Q000276:immunology*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D011877:Radionuclide Imaging; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000728:Androgens; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015021:Yttrium Radioisotopes; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II