A Double Blind Randomized Crossover Study of Oral Thalidomide versus Placebo in Patients with Stage D0 Androgen Dependent Prostate Cancer Following Limited Hormonal Ablation
Androgen deprivation is increasingly being used for the treatment of biochemically recurrent prostate cancer. Thalidomide has been shown to have activity in metastatic prostate cancer.
159 patients enrolled in a double-blind randomized trial to determine if thalidomide can improve the efficacy of gonadotropin receptor hormone agonist (GnRH-A) in hormone-responsive patients with a rising PSA after primary definitive therapy for prostate cancer. Patients were randomized to GnRH-A for six months followed by oral thalidomide 200 mg per day or placebo (Oral Phase A, OPA). At the time of PSA progression, GnRH-A was restarted for six additional months. Patients were then crossed over to the opposite drug and were treated until PSA progression (Oral Phase B, OPB). Testosterone (T) and dihydroxytestosterone (DHT) were likewise monitored throughout the study.
During OPA, the median time to PSA progression was 15 months for thalidomide group compared to 9.6 months on placebo (P=0.21). The median time to PSA progression during OPB for the thalidomide group was 17.1 months versus 6.6 months for the placebo group (P= 0.0002). No differences were observed in time to serum T normalization between the thalidomide arm and placebo arm during both OPA and OPB. Thalidomide was tolerable although dose reductions occurred in 47% (58 of 124 patients).
While thalidomide had no effect on T normalization, there was an observed effect on PSA progression during OPB. This is the first study to demonstrate effects of thalidomide and feasibility of intermittent hormonal therapy for biochemically recurrent prostate cancer.