Unique histological changes in lung metastases of osteosarcoma patients following therapy with liposomal muramyl tripeptide (CGP 19835A lipid)

Abstract

We have recently begun a phase II trial in patients with osteosarcoma who developed pulmonary metastases during adjuvant chemotherapy or who presented with pulmonary metastases that persisted despite chemotherapy. Eligible patients were rendered free of visible disease by surgery. Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTP-PE, CGP 19835A lipid) (2 mg/m2) was infused twice weekly for 3 months. In five patients, a single tumor nodule recurred within 6 weeks after completion of therapy. These lesions were resected and submitted for pathological examination. Tissue specimens obtained after therapy were compared to those obtained before therapy. All the patients showed a histological change in the characteristics of the pulmonary tumors. In three patients, peripheral fibrosis surrounded the tumor and inflammatory cell infiltration and neovascularization were present. This is in contrast to central necrosis, with viable peripheral tumor cells and no inflammatory response observed in lesions resected following chemotherapy. In a fourth case, evidence of early fibrotic changes was found. This and the fifth case showed a change in malignant characteristics, from high grade before liposomal therapy to low grade after therapy. The present study provides evidence for a biological effect of liposomal MTP-PE.

Tumor-Infiltrating Macrophages Are Associated with Metastasis Suppression in High-Grade Osteosarcoma: A Rationale for Treatment with Macrophage Activating Agents

“…A recently published clinical trial has shown improved OS for osteosarcoma patients treated with the macrophage activating agent muramyl tripeptide (MTP) added to the standard chemotherapy regimen (6). However, only limited information on macrophage infiltration and activation in osteosarcoma is available (7).…”

Immunostimulating Agents: What Next?

“…Liposomal MTP-PtdEtn was infused at a dose of 2 mgl mz twice weekly for three months. Histological examination of the tumor nodules recumng after this period showed unique morphological changes marked by peripheral fibrosis surrounding the tumor and inflammatory cell infiltration and/or a change in malignant characteristics from high grade before therapy to low grade after therapy [47]. Killion et al [48], on the other hand, have shown that in mice, oral administration of lipophilic MTP-PtdEtn prevents the monocytopenia induced by chemotherapy (doxorubicin) or whole body X-irradiation, thus adding another aspect to the therapeutic potential of this agent in cancer patients.…”

PharmaForum

“…Das Tumorgewebe hatte sich in allen 5 Fällen histologisch verändert: Bei 3 Patienten konnte eine Infiltra tion mit inflammatorischen Zellen und eine periphere Fibrose um den Tumor herum nachgewiesen werden. Zwei Patienten erreichten eine Änderung der Tumor charakteristika von «hochmaligne» zu «niedrigmaligne» [18]. …”