title: Transdermal estradiol in castrate and chemotherapy resistant prostate cancer.
abstract: BACKGROUND
  Given prior studies demonstrating the marked clinical activity of oral estrogens in prostate cancer, more recent data demonstrating the safety of transdermal estradiol, and the renewed interest in targeting testosterone metabolism and androgen receptor pathways, we report the results of a trial of transdermal estradiol in advanced heavily pre-treated castrate and chemotherapy refractory patients.
  
  
  METHODS
  Patients with prostate cancer progressing after androgen ablation therapy and chemotherapy were treated with transdermal estradiol patches (0.4 mg per 24 hours total) applied weekly and assessed for tolerability and biochemical activity.
  
  
  RESULTS
  Twenty-two patients were treated on study with all patients evaluable for safety and 20 patients evaluable for response. All patients had aggressive and resistant disease, as demonstrated by a median PSA of 170 ng/mL (range 14 to 5030 ng/mL), with more than 60% having been treated with two or more prior chemotherapy regimens, and 20% with visceral disease. Nine patients had a decrease in PSA, of which two patients had a PSA response defined as a decline in PSA by 50%. Therapy was well tolerated and no thrombotic events were observed.
  
  
  CONCLUSIONS
  In heavily pre-treated patients with advanced castrate and chemotherapy refractory metastatic prostate cancer, transdermal estradiol was safe and had biochemical activity. These data support further studies to understand if transdermal estradiol can be useful following multiple standard therapies.
authors.affiliation: The Cancer Institute of New Jersey, UMDNJ-RWJMS, New Brunswick, NJ 08901, USA. steinmn@umdnj.edu
authors.forename: Mark
authors.initials: M
authors.lastname: Stein
authors.forename: Susan
authors.initials: S
authors.lastname: Goodin
authors.forename: Susan
authors.initials: S
authors.lastname: Doyle-Lindrud
authors.forename: Jeffery
authors.initials: J
authors.lastname: Silberberg
authors.forename: Michael
authors.initials: M
authors.lastname: Kane
authors.forename: Dorinda
authors.initials: D
authors.lastname: Metzger
authors.forename: Simantini
authors.initials: S
authors.lastname: Eddy
authors.forename: Weichung
authors.initials: W
authors.lastname: Shih
authors.forename: Robert S
authors.initials: RS
authors.lastname: DiPaola
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D002369:Castration; D003710:Demography; D019008:Drug Resistance, Neoplasm; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000601:surgery*; D013739:Testosterone / Q000097:blood
chemical_list: D013739:Testosterone; D004958:Estradiol