PMID- 1634921
OWN - NLM
STAT- MEDLINE
DCOM- 19920825
LR  - 20231213
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 10
IP  - 8
DP  - 1992 Aug
TI  - Phase II study of liposomal muramyl tripeptide in osteosarcoma: the cytokine 
      cascade and monocyte activation following administration.
PG  - 1310-6
AB  - PURPOSE: A phase II trial that uses liposome-encapsulated muramyl tripeptide 
      phosphatidylethanolamine (L-MTP-PE) in patients with relapsed osteosarcoma is 
      underway. To determine if in vivo cytokine induction plays a role in the 
      mechanism of action of L-MTP-PE, we investigated the circulating cytokine levels 
      of 16 patients who were undergoing therapy. PATIENTS AND METHODS: Patients had 
      histologically proven osteosarcoma and pulmonary metastases that developed either 
      during adjuvant chemotherapy or that were present at diagnosis and persisted 
      despite chemotherapy. Patients were rendered disease-free by surgery. The major 
      goal of the study was to improve the disease-free interval in this high-risk 
      group. L-MTP-PE 2 mg/m2 was infused during a 1-hour period twice a week for 12 
      weeks, then once a week for 12 weeks. Serial blood samples were collected after 
      L-MTP-PE administration and were assayed for cytokine levels (tumor necrosis 
      factor-alpha [TNF alpha] interleukin-1 alpha [IL-1 alpha], IL-1 beta, IL-6, 
      interferon-gamma [IFN-gamma], neopterin, C-reactive protein). RESULTS: After the 
      infusion of L-MTP-PE, there was rapid induction of circulating TNF alpha and 
      IL-6. TNF alpha levels peaked 1 to 2 hours after infusion in 10 of 16 patients, 
      whereas peak IL-6 levels were detected at 2 to 3 hours in all patients. Induction 
      of circulating TNF alpha and IL-6 was evident only after the first dose of 
      L-MTP-PE. Neither IL-1 alpha nor IL-1 beta was detected in the plasma. Neopterin 
      levels increased at 24 hours postinfusion, which indicated macrophage activation, 
      and were not related to the induction of circulating IFN-gamma. C-reactive 
      protein was elevated in all patients at 24 hours and decreased by 72 hours. 
      Unlike circulating TNF alpha and IL-6, elevations in C-reactive protein and 
      neopterin could be detected throughout the treatment course. CONCLUSION: It is 
      concluded that L-MTP-PE has specific biologic effects in patients with 
      osteosarcoma that may be important to the drug's immunostimulatory capacity and 
      its effectiveness as an antitumor agent.
FAU - Kleinerman, E S
AU  - Kleinerman ES
AD  - Department of Cell Biology, University of Texas MD Anderson Cancer Center, 
      Houston 77030.
FAU - Jia, S F
AU  - Jia SF
FAU - Griffin, J
AU  - Griffin J
FAU - Seibel, N L
AU  - Seibel NL
FAU - Benjamin, R S
AU  - Benjamin RS
FAU - Jaffe, N
AU  - Jaffe N
LA  - eng
GR  - CA 42992/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cytokines)
RN  - 0 (Drug Carriers)
RN  - 0 (Liposomes)
RN  - 0 (Phosphatidylethanolamines)
RN  - 1LM890Q4FY (mifamurtide)
RN  - 0 (Biopterins)
RN  - 53678-77-6 (Acetylmuramyl-Alanyl-Isoglutamine)
RN  - 670-65-5 (Neopterin)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Acetylmuramyl-Alanyl-Isoglutamine/*analogs & derivatives/pharmacology/therapeutic 
      use
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Biopterins/analogs & derivatives/blood
MH  - C-Reactive Protein/drug effects
MH  - Cytokines/blood/*drug effects
MH  - Drug Carriers
MH  - Drug Evaluation
MH  - Humans
MH  - Liposomes
MH  - Lung Neoplasms/immunology/secondary
MH  - Monocytes, Activated Killer/*drug effects
MH  - Neopterin
MH  - Osteosarcoma/*drug therapy/*immunology/secondary
MH  - Phosphatidylethanolamines/*pharmacology/therapeutic use
EDAT- 1992/08/01 00:00
MHDA- 1992/08/01 00:01
CRDT- 1992/08/01 00:00
PHST- 1992/08/01 00:00 [pubmed]
PHST- 1992/08/01 00:01 [medline]
PHST- 1992/08/01 00:00 [entrez]
AID - 10.1200/JCO.1992.10.8.1310 [doi]
PST - ppublish
SO  - J Clin Oncol. 1992 Aug;10(8):1310-6. doi: 10.1200/JCO.1992.10.8.1310.