Combination therapy with interferon-γ and interleukin-2 for the treatment of metastatic melanoma

Christina J. Kim, Jeffery K. Taubenberger, Toni B. Simonis, Donald E. White, Steven A. Rosenberg, Francesco M. Marincola

Research output: Contribution to journalArticlepeer-review

Abstract

The toxicity and clinical response to treatment with the combination of interferon-γ (IFN-γ) and interleukin-2 (IL-2) in patients with metastatic melanoma was evaluated. From May 1993 through February 1994, 20 patients were treated with 24 courses of IFN-γ with or without IL-2. A 7-day course of subcutaneous IFN-γ alone was administered to cohorts of two or three patients each at doses of 0.1, 0.2, or 0.3 mg/m2. Thirteen patients received escalating doses of IFN-γ between 0.2 and 0.5 mg/m2 followed by the intravenous (i.v.) administration of IL-2 (720,000 IU/kg) given three times a day. A treatment course consisted of two cycles (maximum of 15 doses of IL-2 per cycle) separated by a 10-day interval. Five additional patients were treated with five courses of IFN-γ, IL-2, and tumor-infiltrating lymphocytes (TILs). All patients treated had the diagnosis of metastatic melanoma. The maximal tolerated dose of subcutaneous IFN-γ was established at 0.3 mg/m2 with dose-limiting hepatotoxicity. Immunohistochemistry analyses showed detectable upregulation of MHC class I alleles in one (8%) of 12 patients. Two of 20 patients who received the combination of IFN-γ and IL-2 had responses, one partial and one complete response. The duration of response was 7 months for the partial response and 12 months for the complete response. IFN-γ was tolerated with minimal side effects of nausea, vomiting, malaise, and decreased hematopoiesis. No increased toxicities were found with the combination treatment, as compared with IL-2 alone. One death occurred on the third day of treatment with IFN-γ alone from hemorrhage into brain metastases. There were no responders in the five patients who received the combination treatment of TIL, IL-2, and IFN-γ. From these findings, we conclude that further studies looking at this combination treatment are not warranted.

Original languageEnglish (US)
Pages (from-to)50-58
Number of pages9
JournalJournal of Immunotherapy
Volume19
Issue number1
DOIs
StatePublished - Jan 1 1996

Keywords

  • Interferon-γ
  • Interleukin-2
  • Melanoma

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Cancer Research

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