TY - JOUR
T1 - Phase II study of liposomal muramyl tripeptide in osteosarcoma
T2 - The cytokine cascade and monocyte activation following administration
AU - Kleinerman, Eugenie S.
AU - Jia, Shu Fang
AU - Griffin, Janet
AU - Seibel, Nita L.
AU - Benjamin, Robert S.
AU - Jaffe, Norman
PY - 1992
Y1 - 1992
N2 - 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 [TNFα] interleukin-1 alpha [IL-1α], IL-1β, IL-6, interferon-gamma [IFN-γ], neopterin, C-reactive protein). Results: After the infusion of L-MTP-PE, there was rapid induction of circulating TNFα and IL-6. TNFα 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 TNFα and IL-6 was evident only after the first dose of L-MTP-PE. Neither IL-1α nor IL-1β 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-γ. C-reactive protein was elevated in all patients at 24 hours and decreased by 72 hours. Unlike circulating TNFα 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.
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 [TNFα] interleukin-1 alpha [IL-1α], IL-1β, IL-6, interferon-gamma [IFN-γ], neopterin, C-reactive protein). Results: After the infusion of L-MTP-PE, there was rapid induction of circulating TNFα and IL-6. TNFα 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 TNFα and IL-6 was evident only after the first dose of L-MTP-PE. Neither IL-1α nor IL-1β 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-γ. C-reactive protein was elevated in all patients at 24 hours and decreased by 72 hours. Unlike circulating TNFα 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.
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U2 - 10.1200/JCO.1992.10.8.1310
DO - 10.1200/JCO.1992.10.8.1310
M3 - Article
C2 - 1634921
AN - SCOPUS:0026631061
SN - 0732-183X
VL - 10
SP - 1310
EP - 1316
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 8
ER -