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01 April 2012

Transdermal estradiol in castrate and chemotherapy resistant prostate cancer

Mark SteinABE, Susan GoodinABE, Susan Doyle-LindrudABE, Jeffery SilberbergBE, MIchael KaneABE, Dorinda MetzgerABE, Simantini EddyABE, Weichung ShihABCE, Robert S. DiPaolaBCDEF

DOI: 10.12659/MSM.882626

Med Sci Monit 2012; 18(4): CR260-264

Abstract

Background: Given prior studies demonstrating the marked clinic 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.
Material/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.

Keywords: Estradiol - therapeutic use, Drug Resistance, Neoplasm, Demography, Castration, Aged, 80 and over, Administration, Cutaneous, Prostatic Neoplasms - surgery, Testosterone - blood

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750