Mifamurtide: a review of its use in the treatment of osteosarcoma.
Mifamurtide (liposomal muramyl tripeptide phosphatidyl ethanolamine; Mepact) is an immunomodulator with antitumor effects that appear to be mediated via activation of monocytes and macrophages. In the EU, mifamurtide is indicated in children, adolescents, and young adults for the treatment of high-grade, resectable, non-metastatic osteosarcoma after macroscopically complete surgical resection; it is administered by intravenous infusion in conjunction with postoperative multiagent chemotherapy. In the US, mifamurtide is currently an investigational agent that holds orphan drug status for the treatment of osteosarcoma. In a large, randomized, open-label, multicenter, phase III trial, the addition of adjuvant (postoperative) mifamurtide to three- or four-drug combination chemotherapy (doxorubicin, cisplatin, and high-dose methotrexate with, or without, ifosfamide) was associated with a statistically significant improvement in overall survival in patients with newly diagnosed, high-grade, non-metastatic, resectable osteosarcoma. The pattern of outcome was generally similar in a small cohort of patients with metastatic disease who were enrolled in this trial. Mifamurtide is generally well tolerated; adverse events attributed to administration of the drug include chills, fever, headache, nausea, and myalgias. Based on the available data, mifamurtide can be considered for inclusion in treatment protocols for localized osteosarcoma.
Frampton
James E
JE
Adis, a Wolters Kluwer Business, Mairangi Bay, North Shore, Auckland, New Zealand. demail@adis.co.nz
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D054796:Drug Dosage Calculations; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010714:Phosphatidylethanolamines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D016207:Cytokines; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine