Influence of bicalutamide with or without tamoxifen or anastrozole on insulin-like growth factor 1 and binding proteins in prostate cancer patients

Int J Biol Markers. 2006 Apr-Jun;21(2):123-6. doi: 10.5301/jbm.2008.4771.

Abstract

Background: There is growing evidence that IGF-1 and binding proteins may be involved in prostate cancer promotion and progression.

Patients and methods: IGF-1 and binding proteins (IGFBP-1 and 3) serum levels were measured at baseline and after 3 and 6 months of treatment in a selected group of patients with prostate cancer who were randomly assigned to treatment with bicalutamide, bicalutamide plus anastrozole or bicalutamide plus tamoxifen in a comparative study investigating the role of pharmacological medication in the development of bicalutamide-induced gynecomastia.

Results: Bicalutamide monotherapy does not appear to alter the IGF-1/IGFBP system. In fact, the increase in IGF-1 levels induced by this treatment was paralleled by comparable increases in binding protein (IGFBP-3). No major changes from baseline up to month 6 either in IGF-1 or in IGFBP-1 and 3 were observed in the bicalutamide plus anastrozole arm. The addition of tamoxifen to bicalutamide produced a sharp decrease in IGF-1 levels (p<0.001) coupled with an increase in both IGFBP-1 (p=0.001) and, to a lesser extent, IGFBP-3 (p=0.5).

Conclusions: The concurrent administration of tamoxifen and bicalutamide reduces the synthesis and bioavailability of IGF-1. Moreover, increased binding protein levels might exert antiproliferative and proapoptotic effects on prostate cancer cells, independently of the IGF-1/IGF receptor-mediated survival system. Both effects might have a synergistic inhibitory influence on prostate cancer growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anastrozole
  • Anilides / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 1 / biosynthesis
  • Insulin-Like Growth Factor Binding Protein 3 / biosynthesis
  • Insulin-Like Growth Factor I / biosynthesis*
  • Male
  • Middle Aged
  • Nitriles / administration & dosage*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism*
  • Tamoxifen / administration & dosage*
  • Tosyl Compounds
  • Triazoles / administration & dosage*

Substances

  • Anilides
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Nitriles
  • Tosyl Compounds
  • Triazoles
  • Tamoxifen
  • Anastrozole
  • Insulin-Like Growth Factor I
  • bicalutamide