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Adjuvant therapy with high-dose interferon α2b in patients with high-risk stage IIB/III melanoma

Nature Clinical Practice Oncology volume 5, pages 2–3 (2008)Cite this article

In 2007, a predictably curative therapy for metastatic melanoma has yet to be identified, but we have begun to understand the immunosuppressive impact of melanoma upon the human host, and how melanoma evades the immune response through the induction of tumor tolerance.1 Interferon α2b (IFN-α2b) at high dosage is critical to the reversal of signaling defects in the T cells of patients with melanoma2 and to the effective polarization of dendritic cells. These immunoregulatory effects have been uniquely achieved with levels of IFNα that are only attainable in vivo using the high-dose regimen of IFN-α2b (HDI) that was originally explored in the trial conducted by the Eastern Cooperative Oncology Group, known as E1684.3

Pathologic evaluation of primary melanoma microstage and the presence of regional draining 'sentinel' nodes reliably predict risks of relapse and mortality. For patients with stage IIB melanoma (classified as cutaneous disease with >4 mm Breslow depth or >2 mm Breslow depth if ulcerated) relapse and mortality risks exceed 35%. For the more advanced disease stage III (regional lymph node involvement), the risk of relapse and death progressively increases with increasing lymph node involvement. Risk of recurrence or death also depends on whether lymph nodes are involved microscopically (stage IIIA) or grossly (stage IIIB), with the risk of disease recurrence ranging from 35% to more than 70%. In 1984, we began trials of HDI for patients with operable but high-risk melanoma (stage IIB and III) in whom microscopic residual melanoma posed an unacceptable risk. We had observed durable long-term remissions in patients with advanced inoperable disease treated with HDI, and noted that the efficacy of this agent seemed greater, the smaller the disease burden. Both of these observations suggested that HDI might cure microscopic residual disease, where no therapy can reliably achieve this goal.

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Author notes

  1. JM Kirkwood is Professor and Vice Chairman for Clinical Research in the Department of Medicine, AA Tarhini and SJ Moschos are Assistant Professors of Medicine in the School of Medicine, Division of Hematology/Oncology, and MC Panelli is Visiting Associate Professor in the Department of Medicine, Division of Hematology/Oncology, and Director of the Immunogenomics and Immunoproteomics Core, all at the University of Pittsburgh, Pittsburgh, PA, USA. JM Kirkwood is also Director and AA Tarhini, SJ Moschos and MC Panelli are Faculty Members of the Melanoma and Skin Cancer Program of the University of Pittsburgh Cancer Institute.

Authors and Affiliations

  1. Department of Medicine, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Research Pavilion 1.32, 5117 Centre Avenue, Pittsburgh, 15213, PA, USA

    John M Kirkwood

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  1. John M Kirkwood
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Correspondence to John M Kirkwood.

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Competing interests

JM Kirkwood is a speaker for Schering-Plough and receives grant/research support from the company. He also receives grant/research support from Roche. The other authors declared no competing interests.

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Kirkwood, J., Tarhini, A., Moschos, S. et al. Adjuvant therapy with high-dose interferon α2b in patients with high-risk stage IIB/III melanoma. Nat Rev Clin Oncol 5, 2–3 (2008). https://doi.org/10.1038/ncponc1004

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