Phase I trial of liposomal muramyl tripeptide phosphatidylethanolamine in cancer patients

J. L. Murray*, E. S. Kleinerman, J. E. Cunningham, J. R. Tatom, K. Andrejcio, J. Lepe-Zuniga, L. M. Lamki, M. G. Rosenblum, H. Frost, J. U. Gutterman, I. J. Fidler, I. H. Krakoff

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Pages (from-to)1915-1925
Number of pages11
JournalJournal of Clinical Oncology
Volume7
Issue number12
Publication statusPublished - 1989

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Murray, J. L., Kleinerman, E. S., Cunningham, J. E., Tatom, J. R., Andrejcio, K., Lepe-Zuniga, J., Lamki, L. M., Rosenblum, M. G., Frost, H., Gutterman, J. U., Fidler, I. J., & Krakoff, I. H. (1989). Phase I trial of liposomal muramyl tripeptide phosphatidylethanolamine in cancer patients. Journal of Clinical Oncology, 7(12), 1915-1925.