ABSTRACT
BACKGROUND: Because neither continuous nor intermittent hormonal therapy is curative, we designed a clinical model to screen new drugs for additive or synergistic effects with hormonal therapy and used IM862, a naturally occurring dipeptide with antiangiogenic and immunomodulatory properties, to test it. METHODS: Patients with prostate cancer who had rising PSA levels after radical prostatectomy and/or radiation therapy were given combined androgen ablation for 3 months. After 2 months' treatment, patients were randomly assigned in a double-blind fashion to receive intranasal IM862 or placebo daily. Treatment continued for 6 months or until disease progression, which was defined by a rising serum PSA level, the appearance of new skeletal or extraskeletal metastatic disease, or new symptoms requiring intervention. RESULTS: Seventy-one patients were evaluable for response. Median time to PSA progression was not reached in either group. At 6 months, disease had progressed in 14 (41%) of the 34 patients receiving treatment and 18 (49%) of the 37 receiving placebo (P = 0.39). No significant toxicities emerged. CONCLUSIONS: The model was demonstrated to be an efficient platform for new drug screening; however, IM862, though well tolerated, failed to demonstrate superiority over placebo in prolonging time to PSA progression.
