Phase I and immunomodulatory study of a muramyl peptide, muramyl tripeptide phosphatidylethanolamine.
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.
Program Resources, Inc., National Cancer Institute-Frederick Cancer Research Facility, Maryland.
W J
WJ
Urba
L C
LC
Hartmann
D L
DL
Longo
R G
RG
Steis
J W
JW
Smith
I
I
Kedar
S
S
Creekmore
M
M
Sznol
K
K
Conlon
W C
WC
Kopp
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use / Q000633:toxicity; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000970:Antineoplastic Agents; D001708:Biopterins / Q000031:analogs & derivatives / Q000096:biosynthesis; D001772:Blood Cell Count / Q000187:drug effects; D002097:C-Reactive Protein / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D004341:Drug Evaluation; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors; D008081:Liposomes; D019798:Neopterin; D010714:Phosphatidylethanolamines / Q000276:immunology / Q000627:therapeutic use* / Q000633:toxicity*; D011961:Receptors, Fc / Q000378:metabolism
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; D006681:HLA-D Antigens; D018950:Lipopolysaccharide Receptors; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011961:Receptors, Fc; C037144:mifamurtide; D001708:Biopterins; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D019798:Neopterin; D007371:Interferon-gamma; D002097:C-Reactive Protein