title: Prostate specific antigen doubling time as auxiliary end point in hormone refractory prostatic carcinoma.
abstract: OBJECTIVE
  In hormone refractory prostatic carcinoma (HRPCa), the majority of patients have bone metastases only, which are by definition non-measurable. This makes objective evaluation of chemotherapeutic agents difficult. Prostate specific antigen (PSA) as a dynamic model was analyzed as potential auxiliary end point in HRPCa.
  
  
  METHODS
  In the framework of a master protocol, the Swiss Group for Clinical Cancer Research (SAKK) is evaluating cytotoxic drugs in HRPCa since 1991. These prospective phase II trials include uniform requirements with regard to response, toxicity and quality of life. From the entire pool of patients, 40 with bidimensionally measurable metastases (lymph nodes, visceral organs) could be identified. PSA doubling time was calculated in patients with a rising PSA during therapy.
  
  
  RESULTS
  Objective best response to any given chemotherapeutic agent was: partial remission (PR) in six patients (15%), stable disease (SD) in 13 (32%) and progressive disease (PD) in 21 (53%). PSA remained stable or decreased in four of six patients with PR (67%), seven of 13 with SD (54%) but only in four of 21 with PD (19%) (Cochran-Armitage test for trend; p=0.015). The median PSA doubling time for patients with a rising PSA was 238 days in PR and 224 days in SD, compared to 113 days in PD (Wilcoxon test; p=0.002).
  
  
  CONCLUSIONS
  PSA doubling time is a potential auxiliary end point in the evaluation of cytotoxic drugs in HRPCa. Thus, also patients with non-measurable (bone) metastases could be included in analysis of response.
authors.affiliation: Department of Urology, Kantonsspital, St. Gallen, Switzerland. hans-peter.schmid@kssg.ch
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Schmid
authors.forename: Rudolf
authors.initials: R
authors.lastname: Morant
authors.forename: Jürg
authors.initials: J
authors.lastname: Bernhard
authors.forename: Rudolf
authors.initials: R
authors.lastname: Maibach
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017322:Clinical Trials, Phase II as Topic; D019008:Drug Resistance, Neoplasm; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D007987:Gonadotropin-Releasing Hormone; D017430:Prostate-Specific Antigen