Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

Abstract

Two clinical protocols are part of this grant application. In 2007, we started the first Phase I dose escalation study with 177Lu-DOTA-huJ591 mAb using dose fractionation regimen. In patients (n=28)with PCa and recurrent and/or metastatic disease, 177Lu dose (20-45 mCi/m2/20 mg antibody) was escalated in 6 different dose levels (3-6 pts at each dose level). 22/28 subjects were done under DOD sponsored protocol. Fractionated 177Lu-J591 is well-tolerated, with reversible myelosuppression. MTD with doses is 40 mCi/m2 (total 80 mCi/m2). The cumulative dose exceeds the single dose MTD (70 mCi/m2). PSA declines have been seen despite a potentially sub-optimal (for 177Lu) patient population with bulky metastatic disease. A second phase I study in combination with docetaxel and 177Lu-J591 (20 mCi/m2; 2 doses) has begun and the first group (n=3) completed. This trial will be completed outside DOD funding. The results of these studies as originally proposed in the grant, clearly demonstrate that the original intent of the SOW have been met and the project can be considered completed. A major reportable outcome is that dose the fractionation of 177Lu-J591 decreases hematological toxicity and appear to result in prolonged PSA declines compared to single higher dose administration. We anticipate that combination therapy may be more efficacious than RIT alone.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2010
Accession Number
ADA540808

Entities

People

  • Shankar Vallabhajosula

Organizations

  • Cornell University

Tags

DTIC Thesaurus Topics

  • Antibodies
  • Antigens
  • Bone Marrow
  • Cancer
  • Cell Physiological Processes
  • Clinical Trials
  • Combination Therapy
  • Department Of Defense
  • Dose Rate
  • Fractionation
  • Hematologic Diseases
  • Medical Personnel
  • Neoplasms
  • Prostate Cancer
  • Radiation
  • Therapy
  • Toxicity

Fields of Study

  • Medicine
  • Physics

Readers

  • Clinical Trial Research.
  • Oncology (Cancer Research).