Phase I evaluation of J591 as a vascular targeting agent in progressive solid tumors Journal Article

Authors: Morris, M. J.; Pandit-Taskar, N.; Divgi, C. R.; Bender, S.; O'Donoghue, J. A.; Nacca, A.; Smith-Jones, P.; Schwartz, L.; Slovin, S.; Finn, R.; Larson, S.; Scher, H. I.
Article Title: Phase I evaluation of J591 as a vascular targeting agent in progressive solid tumors
Abstract: Purpose: The antibody J591 targets the external domain of prostate-specific membrane antigen, which is expressed in the neovasculature of nonprostate solid tumors. This phase I trial tested the hypothesis that J591 could be used as a vascular targeting platform for patients with nonprostate solid tumors. Experimental Design: Patients with progressive solid tumors were eligible. Twenty patients, divided into six dosage cohorts of 3 to 6 patients each, were treated every 3 weeks to a maximum of four doses using either 5, 10, 20, 40, 60, or 100 mg of J591 antibody. Two milligrams of antibody were labeled with 10 mCi of indium-111. Results: Patients with a wide variety of solid tumors were tested; all had good tumor localization. No dose-limiting toxicities were observed. The serum clearance rate decreased with increasing antibody mass, likely a result of early hepatic uptake of antibody. Half-life for each successive cohort was 0.71, 0.84, 1.86, 1.83, 3.32, and 3.56 days. Hepatic saturation seemed to occur by 60 mg. Seventeen of 18 (94%) patients with soft tissue disease on standard scans showed uptake in the soft tissues on antibody scans as did 6 of 6 patients with bone disease. Conclusions: The tumoral neovasculature of a variety of solid tumors can be selectively and safely targeted using J591. In planning for future studies using J591 as a radiation delivery platform, an antibody mass of 60 mg should be considered, as it would seem to minimize the radiation delivered to the liver while minimizing the radiation dose to bone. © 2007 American Association for Cancer Research.
Keywords: adult; clinical article; controlled study; human tissue; aged; aged, 80 and over; middle aged; unclassified drug; clinical trial; area under the curve; solid tumor; neoplasms; tumor localization; controlled clinical trial; antineoplastic activity; neovascularization, pathologic; liver; antibodies, monoclonal; drug distribution; maximum plasma concentration; phase 1 clinical trial; drug half life; indium 111; vascular targeting agent; bone disease; soft tissue disease; j 591
Journal Title: Clinical Cancer Research
Volume: 13
Issue: 9
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2007-05-01
Start Page: 2707
End Page: 2713
Language: English
DOI: 10.1158/1078-0432.ccr-06-2935
PUBMED: 17473203
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 21" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Angelo Nacca
    6 Nacca
  2. Chaitanya Divgi
    160 Divgi
  3. Susan Slovin
    214 Slovin
  4. Michael Morris
    352 Morris
  5. Ronald D Finn
    278 Finn
  6. Lawrence H Schwartz
    282 Schwartz
  7. Steven M Larson
    878 Larson
  8. Howard Scher
    977 Scher
  9. Samantha H Bender
    1 Bender