Effect of Dutasteride on Androgen-Response Gene Expression in Patients With Advanced Prostate Cancer

We have shown in a murine model of treatment with intermittent androgen ablation therapy of
prostate cancer that when dutasteride is given during the regrowth phase (off-phase) of
intermittent therapy, that tumor growth is inhibited and that survival is improved. We have
also shown that testosterone is a more potent inducer of certain tumor suppressor androgen
response genes than dihydrotestosterone. In this murine model, we showed that use of a
5-alpha reductase inhibitor (dutasteride) resulted in significant hyperinduction of the U19
tumor suppressor androgen response gene during the regrowth phase of treatment. In the
current clinical trial, we will determine if use of dutasteride in men with advanced
prostate cancer during the off-phase of intermittent androgen ablation therapy will also
result in hyperinduction of these tumor suppressor androgen response genes. Gene expression
will be measured in tumor tissue obtained by prostate biopsies during the off-phase when the
testosterone level has normalized. PSA levels will also be measured to determine the PSA
doubling time during the off-phase to determine the effect of dutasteride on PSA kinetics.

Inclusion Criteria:

- Histologically proven prostate cancer

- Patients are hormone-naive

- Patients either to begin androgen ablation therapy with LHRH agonist or already
receiving therapy with LHRH agonist

- Advanced prostate cancer with either positive pelvic nodes or bone/visceral
metastasis

- Must have an intact prostate (no previous surgery or XRT)

- ECOG performance status 0-2

- Recovery from any major infection or surgical procedure

- Signed informed consent

Exclusion Criteria:

- Known intolerance or allergy to dutasteride

- Concomitant chemotherapy, biologic therapy, or XRT to prostate

- Bilateral orchiectomy

- Prior malignancy within 5 years of registration