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

Robert S. DiPaola, Robert E. Weiss, Kenneth B. Cummings, Feng Ming Kong, Randy L. Jirtle, Mitchell Anscher, Jose Gallo, Susan Goodin, Sharon Thompson, Zeeshan Rasheed, Joseph Aisner, Mary B. Todd

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23 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1999-2004
Number of pages6
JournalClinical Cancer Research
Volume3
Issue number11
StatePublished - Nov 1997

ASJC Scopus subject areas

  • General Medicine

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