Thorpe JF, Jain S,
Marczylo TH, Gescher AJ, Steward WP, Mellon JK.
Urology Section, Department of Cancer Studies &
Molecular Medicine, University of Leicester, Clinical Sciences
Unit, Leicester General Hospital, Leicester, UK.
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
All phase III trials of prostate cancer chemoprevention were
identified within a Medline search using the keywords “clinical
trial, prostate cancer, chemoprevention”.
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 Prostate Cancer Prevention Trial and the interpretation
of the excess high-grade prostate cancer cases in the finasteride
group. The lack of relationship between cumulative dose and the
high-grade prostate cancer 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 high-grade
prostate cancer 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
Prostate Cancer Prevention Trial . The increased rate of high-grade
prostate cancer in the finasteride group continues to generate
debate; however, finasteride may still be suitable for prostate
cancer prevention, particularly in men with lower urinary