title: A double-blind randomized crossover study of oral thalidomide versus placebo for androgen dependent prostate cancer treated with intermittent androgen ablation.
abstract: OBJECTIVE
  We determined whether thalidomide can prolong progression-free survival in men with biochemically recurrent prostate cancer treated with limited androgen deprivation therapy.
  
  
  METHODS
  A total of 159 patients were enrolled in a double-blind randomized trial to determine if thalidomide can improve the efficacy of a gonadotropin-releasing hormone agonist in hormone responsive patients with an increasing prostate specific antigen after primary definitive therapy for prostate cancer. Patients were randomized to 6 months of gonadotropin-releasing hormone agonist followed by 200 mg per day oral thalidomide or placebo (oral phase A). At the time of prostate specific antigen progression gonadotropin-releasing hormone agonist was restarted for 6 additional months. Patients were then crossed over to the opposite drug and were treated until prostate specific antigen progression (oral phase B). Testosterone and dihydroxytestosterone were likewise monitored throughout the study.
  
  
  RESULTS
  During oral phase A the median time to prostate specific antigen progression was 15 months for the thalidomide group compared to 9.6 months on placebo (p = 0.21). The median time to prostate specific antigen progression during oral phase B for the thalidomide group was 17.1 vs 6.6 months on placebo (p = 0.0002). No differences in time to serum testosterone normalization between the thalidomide and placebo arms were documented during oral phase A and oral phase B. Thalidomide was tolerable although dose reductions occurred in 47% (58 of 124) of patients.
  
  
  CONCLUSIONS
  Despite thalidomide having no effect on testosterone normalization, there was a clear effect on prostate specific antigen progression during oral phase B. This is the first study to our knowledge to demonstrate the effects of thalidomide using intermittent hormonal therapy.
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: Maha H
authors.initials: MH
authors.lastname: Hussain
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.forename: Jeanny B
authors.initials: JB
authors.lastname: Aragon-Ching
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Gurkamal S
authors.initials: GS
authors.lastname: Chatta
authors.forename: Howard
authors.initials: H
authors.lastname: Parnes
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
authors.forename: William L
authors.initials: WL
authors.lastname: Dahut
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000502:physiology; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage*
chemical_list: D000728:Androgens; D020533:Angiogenesis Inhibitors; D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D013792:Thalidomide; D016729:Leuprolide