Back to Search
Start Over
Phase II study of liposomal muramyl tripeptide in osteosarcoma: the cytokine cascade and monocyte activation following administration
- Source :
- Journal of Clinical Oncology. 10:1310-1316
- Publication Year :
- 1992
- Publisher :
- American Society of Clinical Oncology (ASCO), 1992.
-
Abstract
- 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.
- Subjects :
- Cancer Research
Lung Neoplasms
medicine.medical_treatment
Alpha (ethology)
Antineoplastic Agents
Pharmacology
Neopterin
chemistry.chemical_compound
medicine
Humans
Drug Carriers
Osteosarcoma
Chemotherapy
business.industry
Phosphatidylethanolamines
Monocyte
medicine.disease
Biopterin
C-Reactive Protein
Cytokine
medicine.anatomical_structure
Oncology
chemistry
Liposomes
Immunology
Cytokines
Drug Evaluation
Tumor necrosis factor alpha
Monocytes, Activated Killer
business
Acetylmuramyl-Alanyl-Isoglutamine
Mifamurtide
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi.dedup.....31008ebe367ecbed6c5faade2bb929a2