Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer

Prostate. 2012 Apr;72(5):487-98. doi: 10.1002/pros.21449. Epub 2011 Jul 11.

Abstract

Background: We retrospectively explored changes in immunological parameters in men with biochemically recurrent prostate cancer treated with either 5 or 25 mg of lenalidomide in a randomized phase 2 trial, and determined whether those changes correlated with disease progression.

Methods: Cytokine levels were compared for each patient at baseline and after 6 months of treatment with lenalidomide. Regression models for correlated data were used to assess associations of cytokine levels with lenalidomide treatment effect. Estimates were obtained using generalized estimating equations. Changes in circulating anti-prostate antibodies were evaluated using a high-throughput immunoblot technique.

Results: Treatment with lenalidomide was associated with global changes in immunoreactivity to a number of prostate-associated antigens, as well as with changes in circulating levels of the T(H) 2 cytokines IL-4, IL-5, IL-10, and IL-13. Disease progression in treated patients was associated with an increase in circulating IL-8 levels, while IL-8 levels decreased significantly in non-progressors.

Conclusions: Lenalidomide demonstrates immunomodulatory properties in patients with biochemically recurrent prostate cancer. The induction of novel anti-prostate antibodies is a potential mechanism for lenalidomide response. Changes in serum IL-8 levels may serve as a potential biomarker in treated patients. These hypotheses require formal testing in future prospective trials.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / immunology
  • Adenocarcinoma / therapy*
  • Aged
  • Aged, 80 and over
  • Antigens, Surface / immunology
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / immunology
  • Disease Progression
  • Humans
  • Immunomodulation / drug effects
  • Interleukin-8 / metabolism*
  • Lenalidomide
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / immunology
  • Prostate-Specific Antigen / blood
  • Prostate-Specific Antigen / immunology*
  • Prostatectomy
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / therapy*
  • Radiotherapy, Adjuvant
  • Retrospective Studies
  • Thalidomide / analogs & derivatives*
  • Thalidomide / therapeutic use

Substances

  • Antigens, Surface
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Interleukin-8
  • Thalidomide
  • Prostate-Specific Antigen
  • Lenalidomide