Liposomal muramyl tripeptide phosphatidyl ethanolamine: a safe and effective agent against osteosarcoma pulmonary metastases

Abstract

Osteosarcoma is the most common form of primary malignant bone tumor. The use of chemotherapy drugs with many side effects, including high-dose methotrexate, doxorubicin, cisplatin and ifosfamide, has greatly improved osteosarcoma survival compared with surgery alone. However, for 20 years, overall survival remained at a plateau of 60-70% in nonmetastatic disease and 20-30% in metastatic osteosarcoma owing to lung metastases. Liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE) is a new agent that improves overall osteosarcoma survival (chemotherapy without L-MTP-PE 70% versus with L-MTP-PE 78%; p = 0.03). L-MTP-PE offers additional benefit for osteosarcoma treatment in combination with chemotherapy, particularly ifosfamide-containing regimens. Clinical experience indicates that side effects such as fever are temporary and controlled or prevented with ibuprofen and/or acetoaminophen premedication; severe side effects are rare. Although surgery will remain the main approach for osteosarcoma treatment of lung metastases, L-MTP-PE combined with other modalities, including chemotherapy, appears to be of benefit in these patients as well.

The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma

“…The prognostic relevance of the vascular density in osteosarcoma is controversial. However, in a recent study, Kunz et al observed in cohort of 131 patients that the good responders to chemotherapy evidenced a low vascular density of their tumor mass with an improvement of survival as expected [71].…”

“…Mifamurtide) is a synthetic analog of a component of bacterial cell wall which acts as a nonspecific immuno-modulator triggering macrophages and T-cell reaction by the release of soluble mediators [71,72]. The induction of M1-TAMs with anti-tumor activity induced by L-MTP-PE required IFN [73].…”

Mifamurtide for the treatment of nonmetastatic osteosarcoma

“…This group demonstrated that addition of L-MTP-PE to chemotherapy significantly improved overall survival at 6 years from 70% with chemotherapy alone to 78 % with chemotherapy and L-MTP-PE (p = 0.03) [17]. These data demonstrate that L-MTP-PE may have a potential role in the improvement of survival of the osteosarcoma patients remained on a plateau for over two decades [16,[18][19][20]. The proprietary product name of mifamurtide is Mepact ® (Takeda).…”

Synergistic inhibitory effect of apomine and lovastatin on osteosarcoma cell growth

“…Recently, mifamurtide (liposomal muramyl tripeptide phosphatidylethanolamine [L-MTP-PE]) a new therapeutic agent, has been approved in Europe for the treatment of nonmetastatic osteosarcoma with chemotherapy. 3,4 L-MTP-PE is a nonspecific immunomodulator that is a synthetic analog of a component of bacterial cell walls. However, despite these therapeutic advances, limited improvement in survival has been achieved since the mid-1980s.…”