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Mifamurtide

A Review of its Use in the Treatment of Osteosarcoma

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Abstract

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.

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Correspondence to James E. Frampton.

Additional information

Various sections of the manuscript reviewed by: P.M. Anderson, Department of Pediatrics, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA; A.J. Chou, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; N.C. Federman, Pediatrics, UCLA David Geffen School of Medicine, Los Angeles, California, USA; S. Ferrari, SSD Chemioterapia, Istituto Ortopedico Rizzoli, Bologna, Italy; H.J. Kim, Hospital for Special Surgery, New York, New York, USA; D.M. Loeb, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA; K. Mori, Department of Orthopaedic Surgery, Shiga University of Medical Science, Otsu, Japan.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘mifamurtide’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘mifamurtide’ and ‘osteosarcoma’. Searches were last updated 27 April 2010.

Selection: Studies in patients with non-metastatic or metastatic osteosarcoma who received mifamurtide. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Mifamurtide, liposomal muramyl tripeptide phosphatidyl ethanolamine, osteosarcoma, immunomodulation, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

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Frampton, J.E. Mifamurtide. Pediatr-Drugs 12, 141–153 (2010). https://doi.org/10.2165/11204910-000000000-00000

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