Phase I and Immunomodulatory Study of a Muramyl Peptide, Muramyl Tripeptide Phosphatidylethanolamine

Walter J. Urba, Lynn C. Hartmann, Igal Kedar, William C. Kopp, Dan L. Longo, Ronald G. Steis, John W. Smith, Stephen Creekmore, Kevin Conlon, Jeffrey W. Clark, Sandra Snow, Mario Sznol, Christoph Huber, Manfred Herold, W. Gregory Alvord

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37 Scopus citations

Abstract

Muramyl tripeptide phosphatidylethanolamine (MTP-PE; CGP 19835A from Ciba Geigy) is a synthetic muramyl tripeptide structurally related to bacterial cell wall constituents. MTP-PE activates monocytes in vitro to a tumoricidal state and has in vivo antitumor effects in animal models. We studied the toxicity and immunomodulatory effects of once weekly i.v. administration of liposomal-encapsulated MTP-PE for 8 weeks in 27 patients with advanced malignancies. Doses ranged from 0.1 to 2.7 mg/m2. No major tumor responses were seen; 11 patients had stable disease after 8 weeks of therapy and 3 continued on maintenance therapy because of minor tumor regressions and/or clinical improvement. MTP-PE at these doses was well tolerated. Shaking chills and fevers were the most common toxicities and occurred at all dose levels. There was no treatment-induced loss of performance status. Immunomodulatory studies revealed evidence of a biological effect on monocytes. C-reactive protein levels rose in the majority of patients with end-of-treatment values 2 to 10 times higher than baseline. Serum neopterin levels were consistently increased 24 h after MTP-PE administration and significant decreases in expression of two different types of Fc receptors on peripheral blood monocytes were noted 6 h after treatment. Although no major tumor responses were seen in this group of patients with advanced malignancies, MTP-PE was well tolerated and exerted biological effects on monocytes. Serum neopterin levels may be a useful marker for the biological effects of MTP-PE.

Original languageEnglish (US)
Pages (from-to)2979-2986
Number of pages8
JournalCancer research
Volume50
Issue number10
StatePublished - May 15 1990

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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