5α-Reductase Inhibition Coupled with Short Off Cycles Increases Survival in the LNCaP Xenograft Prostate Tumor Model on Intermittent Androgen Deprivation Therapy

Abstract

Purpose Intermittent androgen deprivation therapy (IADT) for patients with PSA progression after treatment for localized prostate cancer is an alternative to the standard continuous ADT. IADT allows for the recovery of testosterone during off-cycles to stimulate regrowth and differentiation of the regressed prostate tumor in order to lessen the side effects of continuous ADT and potentially prolong survival. Previously, IADT coupled with finasteride was shown to prolong survival of animals bearing androgen-sensitive prostate tumors when off-cycle duration was not prolonged and fixed at 10–14 days. Regressed prostate tumor xenografts with testosterone replacement were initially responsive to 5α-reductase inhibition, but resumed growth after several days in the animal models. 5α-reductase inhibition in shorter off-cycles of testosterone recovery could maximize tumor growth inhibition during IADT and perhaps increase survival. Materials and Methods The LNCaP xenograft tumor model was utilized to evaluate the effectiveness of short off-cycles of 4 days coupled with 5α-reductase inhibition on IADT on survival and tumor regrowth. Results Dutasteride inhibited initial testosterone-induced tumor regrowth during both the first and second off-cycle and significantly increased survival. Conclusions These results further support the potential for IADT combined with 5α-reductase inhibition to improve survival in prostate cancer patients when off cycle durations are short or very short.

The Curcumin Derivative, H10, Suppresses Hormone-Dependent Prostate Cancer by Inhibiting 17β-Hydroxysteroid Dehydrogenase Type 3

“…The five groups separately received 0.2 ml of either normal saline (NS), or a solvent comprising 10% DMSO:90% methylcellulose (0.4%, w/ v), or 10 mg/kg of H10, or 30 mg/kg of H10, or 50 mg/kg of H10. The tumor volumes were measured and calculated by the following formula: volume = 0.52 × length × width 2 (Pascal et al, 2014). The body weight and tumor volumes were measured once on every alternate day.…”