PURPOSE: 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). PATIENTS AND 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. CONCLUSION: 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.
PURPOSE: 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). PATIENTS AND 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. CONCLUSION: 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: Andreas Delker; Wolfgang Peter Fendler; Clemens Kratochwil; Anika Brunegraf; Astrid Gosewisch; Franz Josef Gildehaus; Stefan Tritschler; Christian Georg Stief; Klaus Kopka; Uwe Haberkorn; Peter Bartenstein; Guido Böning Journal: Eur J Nucl Med Mol Imaging Date: 2015-08-29 Impact factor: 9.236
Authors: Chan Hyuk Kim; Jun Y Axup; Brian R Lawson; Hwayoung Yun; Virginie Tardif; Sei Hyun Choi; Quan Zhou; Anna Dubrovska; Sandra L Biroc; Robin Marsden; Jason Pinstaff; Vaughn V Smider; Peter G Schultz Journal: Proc Natl Acad Sci U S A Date: 2013-10-14 Impact factor: 11.205
Authors: Neeta Pandit-Taskar; Joseph A O'Donoghue; Jeremy C Durack; Serge K Lyashchenko; Sarah M Cheal; Volkan Beylergil; Robert A Lefkowitz; Jorge A Carrasquillo; Danny F Martinez; Alex Mak Fung; Stephen B Solomon; Mithat Gönen; Glenn Heller; Massimo Loda; David M Nanus; Scott T Tagawa; Jarett L Feldman; Joseph R Osborne; Jason S Lewis; Victor E Reuter; Wolfgang A Weber; Neil H Bander; Howard I Scher; Steven M Larson; Michael J Morris Journal: Clin Cancer Res Date: 2015-07-14 Impact factor: 12.531
Authors: Jorge A Carrasquillo; Bernard M Fine; Neeta Pandit-Taskar; Steven M Larson; Stephen E Fleming; Josef J Fox; Sarah M Cheal; Joseph A O'Donoghue; Shutian Ruan; Govind Ragupathi; Serge K Lyashchenko; John L Humm; Howard I Scher; Mithat Gönen; Simon P Williams; Daniel C Danila; Michael J Morris Journal: J Nucl Med Date: 2019-05-03 Impact factor: 10.057