A review of phase III clinical trials of prostate cancer chemoprevention.
BACKGROUND
Prostate cancer is an excellent target for chemoprevention strategies; given its late age of onset, any delay in carcinogenesis would lead to a reduction in its incidence. This article reviews all the completed and on-going phase III trials in prostate cancer chemoprevention.


METHODS
All phase III trials of prostate cancer chemoprevention were identified within a Medline search using the keywords 'clinical trial, prostate cancer, chemoprevention'.


RESULTS
In 2003, the Prostate Cancer Prevention Trial (PCPT) became the first phase III clinical trial of prostate cancer prevention. This landmark study was terminated early due to the 24.8% reduction of prostate cancer prevalence over a 7-year period in those men taking the 5alpha-reductase inhibitor, finasteride. This article reviews the PCPT and the interpretation of the excess high-grade prostate cancer (HGPC) cases in the finasteride group. The lack of relationship between cumulative dose and the HGPC cases, and the possible sampling error of biopsies due to gland volume reduction in the finasteride group refutes the suggestion that this is a genuine increase in HGPC cases. The other on-going phase III clinical trials of prostate cancer chemoprevention - the REDUCE study using dutasteride, and the SELECT study using vitamin E and selenium - are also reviewed.


CONCLUSIONS
At present, finasteride remains the only intervention shown in long-term prospective phase III clinical trials to reduce the incidence of prostate cancer. Until we have the results of trials using alternative agents including the on-going REDUCE and SELECT trials, the advice given to men interested in prostate cancer prevention must include discussion of the results of the PCPT. The increased rate of HGPC in the finasteride group continues to generate debate; however, finasteride may still be suitable for prostate cancer prevention, particularly in men with lower urinary tract symptoms.
Thorpe
J F
JF
Urology Section, Department of Cancer Studies & Molecular Medicine, University of Leicester, Clinical Sciences Unit, Leicester General Hospital, Leicester, UK. jt104@leicester.ac.uk
Jain
S
S
Marczylo
T H
TH
Gescher
A J
AJ
Steward
W P
WP
Mellon
J K
JK
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001378:Azasteroids / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D000068538:Dutasteride; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018120:Finasteride / Q000627:therapeutic use; D005544:Forecasting; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D018036:Selenium Compounds / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001378:Azasteroids; D004791:Enzyme Inhibitors; D018036:Selenium Compounds; D014810:Vitamin E; D018120:Finasteride; D000068538:Dutasteride