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.