Eligibility and outcomes reporting guidelines for clinical trials for patients in the state of a rising prostate-specific antigen: recommendations from the Prostate-Specific Antigen Working Group. uri icon

Overview

abstract

  • PURPOSE: To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA). HYPOTHESIS: A clinical states framework was used to address the hypothesis that definitive phase III trials could not be conducted in this patient population. PATIENT POPULATION: The Group focused on men with systemic (nonlocalized) recurrence and a defined risk of developing clinically detectable metastases. Models to define systemic versus local recurrence, and risk of metastatic progression were discussed. INTERVENTION: Therapies that have shown favorable effects in more advanced clinical states; meaningful biologic surrogates of activity linked with efficacy in other tumor types; and/or effects on a target or pathway known to contribute to prostate cancer progression in this state can be considered for evaluation. OUTCOMES: An intervention-specific posttherapy PSA-based outcome definition that would justify further testing should be described at the outset. Reporting: Trial reports should include a table showing the number of patients who achieve a specific PSA-based outcome, the number who remain enrolled onto the trial, and the number who came off study at different time points. The term PSA response should be abandoned. TRIAL DESIGN: The phases of drug development for this state are optimizing dose and schedule, demonstration of a treatment effect, and clinical benefit. To move a drug forward should require a high bar that includes no rise in PSA in a defined proportion of patients for a specified period of time at a minimum. Agents that do not produce this effect can only be tested in combination. The preferred end point of clinical benefit is prostate cancer-specific survival; the time to development of metastatic disease is an alternative. CONCLUSION: Methodology to show that an intervention alters the natural history of prostate cancer is described. At each stage of development, only agents with sufficient activity should be moved forward.

authors

  • Scher, Howard
  • Eisenberger, Mario
  • D'Amico, Anthony V
  • Halabi, Susan
  • Small, Eric J
  • Morris, Michael J.
  • Kattan, Michael W
  • Roach, Mack
  • Kantoff, Philip
  • Pienta, Kenneth J
  • Carducci, Michael A
  • Agus, David
  • Slovin, Susan Faith
  • Heller, Glenn
  • Kelly, William Kevin
  • Lange, Paul H
  • Petrylak, Daniel
  • Berg, William
  • Higano, Celestra
  • Wilding, George
  • Moul, Judd W
  • Partin, Alan N
  • Logothetis, Christopher
  • Soule, Howard R

publication date

  • February 1, 2004

Research

keywords

  • Prostate-Specific Antigen
  • Prostatic Neoplasms

Identity

Scopus Document Identifier

  • 1442290324

Digital Object Identifier (DOI)

  • 10.1200/JCO.2004.07.099

PubMed ID

  • 14752077

Additional Document Info

volume

  • 22

issue

  • 3