Effect of P-30 protein and tamoxifen on transforming growth factor-β1 in patients with rising prostate specific antigen

J. E. Eid, M. Brunner, K. B. Cummings, R. E. Weiss, Susan Goodin, Joseph Aisner, M. Todd, R. S. DiPaola

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: The P-30 protein (P30), a novel RNase, in combination with tamoxifen (TAM) has anti-tumor activity in vitro and in patients with pancreatic cancer. Proposed mechanisms of TAM activity include the induction of the inhibitory growth factor transforming growth factor-β1 (TGF-β1) and reduction 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 limitation of using PSA alone as marker of anti-tumor activity, plasma TGF-β1 and IGF-1 were measured as potential markers of drug activity. Methods: Thirteen patients with rising PSA after local therapy for cancer of the prostate were enrolled and 11 patients were treated with Tamoxifen 20mg BID daily and P30, 480 μg/m2 IV weekly. Patients were followed clinically. Serum PSA, Plasma TGF-β1 and plasma IGF-1 were measured by ELISA. Results: One of 5 patients who completed 3 months of therapy had stabilization of PSA. Six 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-β1 in 6/8 patients over the first month (p=0.15). Conclusions: P30 and TAM had minimal effect on PSA levels and was limited secondary to toxicity. The combination increased levels of TGF-β1 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 treated with TAM or other agents capable of modulating TGF-β1 or IGF-1.

Original languageEnglish (US)
Pages (from-to)243-247
Number of pages5
JournalUrologic Oncology
Volume6
Issue number6
DOIs
StatePublished - Nov 27 2001

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

Keywords

  • Hormone refractory prostate cancer
  • Prostate specific antigen
  • Ribonuclease

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