TY - JOUR
T1 - Phase I trial of liposomal muramyl tripeptide phosphatidylethanolamine in cancer patients
AU - Murray, J. L.
AU - Kleinerman, E. S.
AU - Cunningham, J. E.
AU - Tatom, J. R.
AU - Andrejcio, K.
AU - Lepe-Zuniga, J.
AU - Lamki, L. M.
AU - Rosenblum, M. G.
AU - Frost, H.
AU - Gutterman, J. U.
AU - Fidler, I. J.
AU - Krakoff, I. H.
PY - 1989
Y1 - 1989
N2 - Twenty-eight evaluable patients with metastatic cancer refractory to standard therapy received escalating doses of muramyl tripeptide phosphatidylethanolamine (MTP-PE) (.05 and 12 mg/m2) in phosphatidylserine (PC):phosphatidylcholine (PS) liposomes (lipid:MTP-PE ratio 250:1). Liposomal MTP-PE (L-MTP-PE) was infused over 1 hour twice weekly; doses were escalated within individual patients every 3 weeks as tolerated for a total treatment duration of 9 weeks. Routine clinical laboratory parameters, acute phase reactants and various immunologic tests were monitored at various time points during treatment. Toxicity was moderate (≤ grade II) in 24 patients with chief side effects being chills (80% of patients), fever (70%), malaise (60%), and nausea (55%). In four patients L-MTP-PE treatment was deescalated due to severe malaise and recurrent fever higher than 38.8°C. The maximum-tolerated dose (MTD) was 6 mg/m2. Significant (P < .05) increases in WBC count, absolute granulocyte count, ceruloplasmin, β2-microglobulin, c-reactive protein, monocyte tumoricidal activity, and serum IL-1β were found. Significant decreases in serum cholesterol were also observed. Clearance of intravenously (iv)-infused technetium-99 (99mTc)-labeled liposomes containing MTP-PE in four patients was biphasic; gamma camera scans revealed uptake of radiolabel in liver, spleen, lung, nasopharynx, thyroid gland, and tumor (two patients). No objective tumor regression was seen. In view of its definite immunobiologic activity and lack of major toxicity, additional phase II and adjuvant trials of L-MTP-PE are warranted.
AB - Twenty-eight evaluable patients with metastatic cancer refractory to standard therapy received escalating doses of muramyl tripeptide phosphatidylethanolamine (MTP-PE) (.05 and 12 mg/m2) in phosphatidylserine (PC):phosphatidylcholine (PS) liposomes (lipid:MTP-PE ratio 250:1). Liposomal MTP-PE (L-MTP-PE) was infused over 1 hour twice weekly; doses were escalated within individual patients every 3 weeks as tolerated for a total treatment duration of 9 weeks. Routine clinical laboratory parameters, acute phase reactants and various immunologic tests were monitored at various time points during treatment. Toxicity was moderate (≤ grade II) in 24 patients with chief side effects being chills (80% of patients), fever (70%), malaise (60%), and nausea (55%). In four patients L-MTP-PE treatment was deescalated due to severe malaise and recurrent fever higher than 38.8°C. The maximum-tolerated dose (MTD) was 6 mg/m2. Significant (P < .05) increases in WBC count, absolute granulocyte count, ceruloplasmin, β2-microglobulin, c-reactive protein, monocyte tumoricidal activity, and serum IL-1β were found. Significant decreases in serum cholesterol were also observed. Clearance of intravenously (iv)-infused technetium-99 (99mTc)-labeled liposomes containing MTP-PE in four patients was biphasic; gamma camera scans revealed uptake of radiolabel in liver, spleen, lung, nasopharynx, thyroid gland, and tumor (two patients). No objective tumor regression was seen. In view of its definite immunobiologic activity and lack of major toxicity, additional phase II and adjuvant trials of L-MTP-PE are warranted.
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U2 - 10.1200/JCO.1989.7.12.1915
DO - 10.1200/JCO.1989.7.12.1915
M3 - Article
C2 - 2479721
AN - SCOPUS:0024789583
SN - 0732-183X
VL - 7
SP - 1915
EP - 1925
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 12
ER -