Can J Urol. 2009 Oct;16(5):4806-12.
and bicalutamide in patients with hormone-refractory prostate cancer:
the Therapy Assessed by Rising PSA (TARP) study rationale and design.
Sartor O, Gomella LG, Gagnier P, Melich K, Dann R.
Tulane Cancer Center, New Orleans, Louisiana, USA.
Bicalutamide blocks androgen action in men with prostate cancer but has
low affinity for the androgen receptor compared to dihydrotestosterone
(DHT). Dutasteride, a dual 5-reductase inhibitor (5ARI), blocks the
conversion of testosterone to DHT, reduces tumor volume and improves
PSA in prostate cancer. Bicalutamide should be a more effective
antiandrogen if it competes against intraprostatic testosterone, rather
than DHT, for the androgen receptor. The Therapy Assessed by Rising PSA
(TARP) study investigates dutasteride in combination with bicalutamide
to prevent or delay disease progression in patients with
castrate-refractory prostate cancer (CRPC) after initial androgen
PATIENTS AND METHODS: This ongoing US and Canada
multicenter trial with patients with rising PSAs while on a GnRH
analogue are randomized to double-blind treatment with dutasteride 3.5
mg and bicalutamide 50 mg or placebo and bicalutamide 50 mg once daily.
Inclusion criteria include three rising PSA levels despite a GnRH
analogue or surgical castration, and no radiographic evidence of
metastases. The entry PSA values must be 2.0 ng/ml-20.0 ng/ml and serum
testosterone level < 50 ng/dl. The primary endpoint is time to
disease progression determined by PSA, or radiographic progression.
CONCLUSIONS: TARP will be the first study to evaluate the effects of
dutasteride and an antiandrogen in patients failing GnRH analogue and
help elucidate the potential role of a dual 5ARI in reducing the rate
of progression in non-metastatic CRPC.