Phase II study of lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer Journal Article


Authors: Tagawa, S. T.; Milowsky, M. I.; Morris, M.; Vallabhajosula, S.; Christos, P.; Akhtar, N. H.; Osborne, J.; Goldsmith, S. J.; Larson, S.; Taskar, N. P.; Scher, H. I.; Bander, N. H.; Nanus, D. M.
Article Title: Phase II study of lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer
Abstract: Purpose: To assess the efficacy of a single infusion of radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (lutetium-177; 177Lu) by prostate-specific antigen (PSA) decline, measurable disease response, and survival. Experimental Design: In this dual-center phase II study, two cohorts with progressive metastatic castration-resistant prostate cancer received one dose of 177Lu-J591 (15 patients at 65 mCi/m2, 17 at 70 mCi/m2) with radionuclide imaging. Expansion cohort (n = 15) received 70 mCi/m2 to verify response rate and examine biomarkers. Results: Forty-seven patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received 177Lu-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 Imaximumtolerated dose (70mCi/m2) resulted in more30%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. Conclusion: A single dose of 177Lu-J591 was well tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose response. Imaging biomarkers seem promising. © 2013 American Association for Cancer Research.
Journal Title: Clinical Cancer Research
Volume: 19
Issue: 18
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2013-09-15
Start Page: 5182
End Page: 5191
Language: English
DOI: 10.1158/1078-0432.ccr-13-0231
PROVIDER: scopus
PMCID: PMC3778101
PUBMED: 23714732
DOI/URL:
Notes: --- - Cited By (since 1996):1 - "Export Date: 1 November 2013" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Joseph R Osborne
    57 Osborne
  2. Michael Morris
    277 Morris
  3. Neil Harrison Bander
    30 Bander
  4. Steven M Larson
    774 Larson
  5. Howard Scher
    833 Scher