Twenty-eight evaluable patients with metastatic
cancer refractory to standard
therapy received escalating doses of
muramyl tripeptide phosphatidylethanolamine (MTP-PE) (.05 to 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 (less than or equal to 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 degrees C. The maximum-tolerated dose (MTD) was 6 mg/m2. Significant (P less than .05) increases in WBC count, absolute granulocyte count,
ceruloplasmin,
beta 2-microglobulin,
c-reactive protein, monocyte tumoricidal activity, and serum IL-1 beta 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.