Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Mifamurtide: a review of its use in the treatment of osteosarcoma. 2048 44

Mifamurtide, also known as liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE), has been approved for the treatment of osteosarcoma in Europe. Mifamurtide's rational drug design employs MTP-PE for macrophage activation in a multilamellar liposome drug carrier, containing the synthetic phospholipids 1-palmitoyl-2-oleoyl phosphatidyl choline (POPC) and 1,2-dioleoyl phosphatidyl serine (OOPS). Although the drug is not cytotoxic towards normal or tumor cells in vitro, immune activation against osteosarcoma lung metastases in vivo accounts for mifamurtide's antiosteosarcoma effects. Phosphatidyl serine-containing lipids signal macrophage cells that have "flipped phosphatidyl serine" to the outer membrane after apoptosis (e.g., after damage of tumor cells from chemotherapy); thus, both mifamurtide's active and inactive ingredients target immune cells in the lungs. Mifamurtide administration has resulted in 8% and 13% improvement in 6- and 5-year overall survivals, when added to chemotherapy in nonmetastatic and metastatic patients with osteosarcoma, respectively. The short-term toxicities of mifamurtide (fever, headache, flu-like symptoms and rigors) are reduced or eliminated using ibuprofen (200 mg) as premedication for the first infusion; an algorithm for pre- and postmedication is presented. To date, no long-term side effects of mifamurtide have been reported. Compassionate access programs based in two major cancer centers (MD Anderson and Memorial Sloan-Kettering), have recently provided this potentially life-saving drug in North America. The experience with mifamurtide provides an outstanding example of successful cooperation among regulatory bodies and agencies, the pharmaceutical industry and pediatric oncologists to improve cancer care and outcomes for children and young people with a rare sarcoma.
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PMID:Mifamurtide in osteosarcoma--a practical review. 2051 34