Dutasteride and bicalutamide in patients with hormone-refractory prostate cancer: the Therapy Assessed by Rising PSA (TARP) study rationale and design.

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 deprivation therapy.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.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.