Initial clinical trial of the macrophage activator muramyl tripeptide-phosphatidylethanolamine encapsulated in liposomes in patients with advanced cancer.
A phase I clinical trial of the macrophage activator, muramyl tripeptide-phosphatidylethanolamine has been carried out in 37 patients (47 courses) at doses of 0.01-6.0 mg/m2 intravenously twice weekly for 4 weeks. Activation of peripheral blood monocytes and drug toxicity were used as the parameters to monitor the trial. Toxicity was acute systemic responses of fever, chills, and hypertension without a clear dose response. No major organ-related toxicity was seen. A dose of 4.0 mg/m2 biweekly produced activation of blood monocytes; a dose of 6.0 mg/m2 produced inhibition. There was one complete response of 3 months duration in a patient with renal cell carcinoma with pulmonary metastases. The optimum dose for phase II studies is in the range of 1-4 mg/m2 twice weekly for 4 weeks, a dose that is well tolerated.
Creaven
P J
PJ
Department of Medicine, Roswell Park Memorial Institute, Buffalo, NY 14263.
Cowens
J W
JW
Brenner
D E
DE
Dadey
B M
BM
Han
T
T
Huben
R
R
Karakousis
C
C
Frost
H
H
LeSher
D
D
Hanagan
J
J
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D004337:Drug Carriers; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008081:Liposomes; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D010714:Phosphatidylethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index
D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine