Serum TNF-α, B2M and sIL-2R levels are biological correlates of outcome in adjuvant IFN-α2b treatment of patients with melanoma

J Cancer Res Clin Oncol. 2011 Mar;137(3):455-62. doi: 10.1007/s00432-010-0900-1. Epub 2010 May 9.


Purpose: There are no biological markers available to predict outcome in melanoma patients treated with adjuvant interferon-alpha (IFN-α). The clinical activity of IFN-α is thought to be mediated not only by anti-proliferative effects, but also by induction and modulation of secondary cytokines. We examined serum cytokine levels in IFN-α-treated patients to find potential biological markers for response or toxicity.

Patients and methods: In a prospective randomized trial, 66 stages II and III melanoma patients underwent an induction treatment of 10 MU IFN α2b s.c. 5 ×/week, followed by either 5 MU or 10 MU IFN α2b s.c. 3 ×/week for a total of 2 years. Serial measurements of serum IL-1β, IL-2, sIL-2R, IL-6, IL-10, TNF-α and β-2 microglobulin (B2M) were taken. Two factorial analysis of repeated measurements (ANOVA) as well as univariate and multivariate analyses was used to identify prognostic factors for relapse and toxicity.

Results: TNF-α levels correlated with toxicity. In patients with relapse, significantly lower levels of TNF-α were detected at baseline and throughout therapy compared with patients without relapse. B2M and sIL-2R showed a significant increase throughout the therapy phase. At baseline, the combination of TNF-α, B2M and sIL-2R revealed a positive predictive value for relapse of 82.9% in the multivariate analyses.

Conclusion: Low TNF-α levels are negatively associated with relapse-free survival. Conversely, high TNF-α levels are correlated with toxicity but seem to be beneficial to patients with regard to relapse-free survival. B2M and sIL-2R are biological markers of adjuvant IFN-α2b treatment.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / adverse effects
  • Interleukins / blood
  • Male
  • Melanoma / blood*
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Prospective Studies
  • Receptors, Interleukin-2 / blood*
  • Recombinant Proteins
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood*
  • Young Adult
  • beta 2-Microglobulin / blood*


  • Antineoplastic Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • beta 2-Microglobulin