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J Clin Oncol. 2006 Jul 1;24(19):3164-71.

Neoadjuvant treatment of regional stage IIIB melanoma with high-dose interferon alfa-2b induces objective tumor regression in association with modulation of tumor infiltrating host cellular immune responses.

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1
Melanoma and Skin Cancer Program, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Abstract

PURPOSE:

Adjuvant high-dose interferon-alfa-2b (HDI) improves disease-free and overall survival in patients with high-risk melanoma. However, its mechanism of action is largely unknown. Therefore, HDI was investigated in the neoadjuvant setting to assess clinical and pathologic responses after 4 weeks of HDI and to perform immunohistochemical evaluation of immune cell subsets and melanoma-associated antigens.

PATIENTS AND METHODS:

Patients with palpable regional lymph node metastases from melanoma (American Joint Committee on Cancer stage IIIB-C) underwent surgical biopsy at study entry and then received standard intravenous HDI (20 million units/m2, 5 days per week) for 4 weeks followed by complete lymphadenectomy and standard maintenance subcutaneous HDI (10 million units/m2 3 times per week) for 48 weeks. Biopsy samples were obtained before and after intravenous HDI and subjected to immunohistochemical analysis as well as routine pathologic study.

RESULTS:

Twenty patients were enrolled, and biopsy samples were informative for 17. Eleven patients (55%) demonstrated objective clinical response, and 3 patients (15%) had complete pathologic response. At a median follow-up of 18.5 months (range, 7 months to 50 months) 10 patients had no evidence of recurrent disease. Clinical responders had significantly greater increases in endotumoral CD11c+ and CD3+ cells and significantly greater decreases in endotumoral CD83+ cells compared with nonresponders. No changes in the expression of melanoma-associated lineage antigens, tumor cell proliferation, angiogenesis, or apoptosis were evident.

CONCLUSION:

Neoadjuvant HDI is highly effective for the treatment of palpable stage IIIB-C melanoma, and the findings of this study implicate an indirect immunomodulatory mechanism rather than a direct antitumor mechanism.

PMID:
16809739
DOI:
10.1200/JCO.2005.05.2498
[Indexed for MEDLINE]
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