Improving intermittent androgen deprivation therapy: lessons learned from basic and translational research

Intermittent androgen deprivation therapy (IADT) is an alternative to continuous androgen deprivation therapy (ADT) in prostate cancer patients with nonmetastatic disease. ADT is associated with numerous side effects such as hot flashes, sexual dysfunction, anemia, fatigue, loss of muscle mass, osteoporosis, metabolic syndrome and premature cardiovascular disease. IADT was developed with the intention of improving the quality of life and to delay progression of prostate cancer to castration resistance. The benefits of slightly improved quality of life by IADT compared to ADT were demonstrated in multiple clinical trials. IADT was noted to be noninferior to ADT in patients with biochemical recurrence of prostate cancer but in studies performed in patients with metastatic prostate cancer, the results were inconclusive. Our recent studies suggested that the administration of 5 alpha-reductase inhibitors during the off-cycle of IADT can significantly prolong the survival of mice bearing androgen-sensitive prostate tumors when off-cycle duration was short. This review discusses the survival benefit of 5 alpha-reductase inhibition in IADT in animal models and the potential translation of this finding into clinic.