Effect of P-30 protein and tamoxifen on transforming growth factor-beta 1 in patients with rising prostate specific antigen

Objectives: The P-30 protein (P30), a novel RNase, in combination with tamo xifen (TAM) has anti-tumor activity in vitro and in patients with pancreati c cancer. Proposed mechanisms of TAM activity include the induction of the inhibitory growth factor transforming growth factor-PI (TGF-beta1) and redu ction of the tumor mitogen insulin like growth factor-1 (IGF-1). This study was designed to determine if P30 and TAM reduced prostate specific antigen (PSA) in patients with early prostate cancer recurrence. Given the limitat ion of using PSA alone as marker of anti-tumor activity, plasma TGF-beta1 a nd IGF-1 were measured as potential markers of drug activity. Methods: Thir teen patients with rising PSA after local therapy for cancer of the prostat e were enrolled and 11 patients were treated with Tamoxifen 20mg BID daily and P30, 480 mug/m(2) IV weekly. Patients were followed clinically. Serum P SA, Plasma TGF-beta1 and plasma IGF-1 were measured by ELISA. Results: One of 5 patients who completed 3 months of therapy had stabilization of PSA. S ix patients discontinued therapy secondary to toxicity before completing 3 cycles. Despite minimal effect on PSA, this therapy decreased plasma IGF-1 in 7/8 patients (p=0.02). There was no significant increase in TGF-beta1 in 6/8 patients over the first month (p=0.15). Conclusions: P30 and TAM had m inimal effect on PSA levels and was limited secondary to toxicity. The comb ination increased levels of TGF-beta1 and decreased IGF-1 in most patients. Further studies are warranted to determine if these measurements correlate to anti-tumor activity better than PSA in patients with prostate cancer tr eated with TAM or other agents capable of modulating TGF-beta1 or IGF-1. (C ) 2001 Elsevier Science Inc. All rights reserved.