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

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Abstract

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.

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Acknowledgments

This trial was supported by a grant from Essex Pharma GmbH, Munich, Germany. We thank Ulrich Keilholz, M.D., for critically reading the manuscript and for constructive comments.

Conflict of interest statement

All authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Dermatology and Allergy, Skin Cancer and Melanoma Center, Charité, Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Maja A. Hofmann, Felix Kiecker, Christian Kors & Uwe Trefzer

  2. Institute of Medical Biostatistics, Charité, Universitätsmedizin Berlin, Berlin, Germany

    Ingeborg Küchler

Authors
  1. Maja A. Hofmann
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  2. Felix Kiecker
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  3. Ingeborg Küchler
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  4. Christian Kors
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  5. Uwe Trefzer
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Correspondence to Maja A. Hofmann.

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Hofmann, M.A., Kiecker, F., Küchler, I. et al. 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 137, 455–462 (2011). https://doi.org/10.1007/s00432-010-0900-1

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  • DOI: https://doi.org/10.1007/s00432-010-0900-1

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