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.