|
Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 4676
© 2005 American Society of Clinical Oncology
A systematic review of the safety and efficacy of parenteral estrogens in prostate cancer
R. Langley,
G. Norman,
M. Emmans Dean,
Z. Hodges,
G. Ritchie,
K. Light,
M. Sydes,
M. Parmar,
P. Abel and
A. Eastwood
MRC Clin Trials Unit, London, United Kingdom; Centres for Reviews and Dissemination, York, United Kingdom; Imperial Coll, London, United Kingdom
4676
Background: The increasing and prolonged use of Luteinizing-Hormone Releasing Hormone (LHRH) analogues in the management of prostate cancer has highlighted concerns about long-term toxicity particularly osteoporosis. Oral estrogens are effective at producing castrate levels of testosterone but are not used because of cardiovascular (CVS) toxicity which has been attributed to first-pass hepatic metabolism. Administering estrogen through a transdermal patch should avoid CVS toxicity and osteoporosis. This review was undertaken to assess the safety and efficacy of parenteral estrogens in order to inform the design of a clinical trial. Methods: Eighteen electronic databases and appropriate paper and internet resources were searched for randomised-controlled trials comparing parenteral estrogen with other therapies in prostate cancer. Results: Seventeen trials were found. 9 assessed parenteral estrogens alone, 8 in combination with other treatments. The evidence was heterogeneous and some was of uncertain metholodogical quality. The majority of trials assessed intramuscular poyestradiol phosphate (PEP), no randomised evidence on the use of transdermal patches was found. PEP in a dose sufficient to produce castrate levels of testosterone, may be as effective as other hormonal treatments in controlling prostate cancer, measured in terms of disease-free and overall survival. At lower doses PEP was less effective. CVS mortality was not increased by the use of PEP alone compared to other hormonal treatments although the incidence of non-fatal CVS morbidity was increased. CVS toxicity was increased by the use of PEP in combination with low dose oral estrogen. Conclusions: There was insufficient evidence to determine the safety and efficacy of parenteral oestrogens conclusively. However, parenteral estrogen alone appears to be an effective treatment for prostate cancer with no associated increase in CVS mortality, although there may be an increase in non-fatal CVS morbidity. A randomized feasibility study comparing LHRH to transdermal estrogen is planned for men with locally advanced or metastatic prostate cancer.
No significant financial relationships to disclose.
|
