title: Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group.
abstract: OBJECTIVE
  Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival. Since the majority of phase II clinical trials for patients with androgen-independent prostate cancer (AIPC) have used PSA as a marker, we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting. We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters.
  
  
  RESULTS
  We defined four patient groups: (1) progressive measurable disease, (2) progressive bone metastasis, (3) stable metastases and a rising PSA, and (4) rising PSA and no other evidence of metastatic disease. The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials. We propose that investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period. Some investigators may want to report additional measures of PSA changes (ie, 75% decline, 90% decline). Response duration and the time to PSA progression may also be important clinical end point.
  
  
  CONCLUSIONS
  Through this consensus conference, we believe we have developed practical guidelines for using PSA as a measurement of outcome. Furthermore, the use of common standards is important as we determine which agents should progress to randomized trials which will use survival as an end point.
authors.affiliation: Beth Israel Deaconess Medical Center, Dana Farber Cancer Center, and Massachusetts General Hospital, Boston, MA, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Bubley
authors.forename: M
authors.initials: M
authors.lastname: Carducci
authors.forename: W
authors.initials: W
authors.lastname: Dahut
authors.forename: N
authors.initials: N
authors.lastname: Dawson
authors.forename: D
authors.initials: D
authors.lastname: Daliani
authors.forename: M
authors.initials: M
authors.lastname: Eisenberger
authors.forename: W D
authors.initials: WD
authors.lastname: Figg
authors.forename: B
authors.initials: B
authors.lastname: Freidlin
authors.forename: S
authors.initials: S
authors.lastname: Halabi
authors.forename: G
authors.initials: G
authors.lastname: Hudes
authors.forename: M
authors.initials: M
authors.lastname: Hussain
authors.forename: R
authors.initials: R
authors.lastname: Kaplan
authors.forename: C
authors.initials: C
authors.lastname: Myers
authors.forename: W
authors.initials: W
authors.lastname: Oh
authors.forename: D P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: E
authors.initials: E
authors.lastname: Reed
authors.forename: B
authors.initials: B
authors.lastname: Roth
authors.forename: O
authors.initials: O
authors.lastname: Sartor
authors.forename: H
authors.initials: H
authors.lastname: Scher
authors.forename: J
authors.initials: J
authors.lastname: Simons
authors.forename: V
authors.initials: V
authors.lastname: Sinibaldi
authors.forename: E J
authors.initials: EJ
authors.lastname: Small
authors.forename: M R
authors.initials: MR
authors.lastname: Smith
authors.forename: D L
authors.initials: DL
authors.lastname: Trump
authors.forename: G
authors.initials: G
authors.lastname: Wilding
mesh_terms: D000728:Androgens / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic / Q000592:standards*; D015975:Consensus Development Conferences, NIH as Topic; D017408:Guidelines as Topic; D006801:Humans; D008297:Male; D018579:Patient Selection; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy; D012016:Reference Values; D014481:United States
chemical_list: D000728:Androgens; D017430:Prostate-Specific Antigen