Effect of 13-cis-retinoic acid and α-interferon on transforming growth factor in patients with rising prostate-specific antigen

The objective of this study was to test the hypothesis that 13-cis- retinoic acid (CRA) and α-interferon (IFN-α) have antitumor activity in patients with early recurrence of prostate cancer measured by rising prostate-specific antigen (PSA) after local therapy, and that this activity is associated with the increase of plasma transforming growth factor β1 (TGF-β1). Thirty patients with a PSA > 7 ng/ml that increased >0.4 ng/ml/month after initial radiation therapy or a PSA > 2.0 ng/ml after prostatectomy were treated with 1 mg/kg/day of CRA and 3 million units of IFN-α administered three times per week. Patients were followed clinically with serum measurements of PSA and assessment of toxicity. Biological activity of CRA and IFN-α was assessed by the measurement of plasma TGF- β1. Twenty-six percent of patients had a partial (50% decrease maintained for 1 month) or minimal (<50% decrease maintained for 1 month) biochemical response of PSA, with a median decrease of 23% (11-55%) at 3 months. Plasma TGF-β1 levels increased with CRA and IFN-α therapy and correlated with a decrease in PSA; patients with a decrease in PSA had a 151% increase in TGF- β1 compared to 27% in patients without a decrease in PSA (P = 0.04). CRA and IFN-α can produce transient reduction or stabilization of PSA. The measurement of plasma TGF-β1 at 1 month of therapy correlates with changes in PSA and may represent a useful marker for the biological effect of these agents; further analysis in larger numbers of patients and methods to optimize these effects should be explored.