title: Current studies of liposome muramyl tripeptide (CGP 19835A lipid) therapy for metastasis in spontaneous tumors: a progress review.
abstract: Targeted delivery of macrophage activating agents is an attractive approach to treat micrometastatic disease. Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a potent activator of monocytes/macrophages in humans, mice, and dogs. We have conducted clinical trials in dogs with malignant and highly metastatic spontaneous tumors. Presented are results of our trials evaluating L-MTP-PE in combination with surgery and chemotherapy in dogs with spontaneous osteosarcoma and hemangiosarcoma, particularly relevant malignancies having having many similarities to human cancer. Osteosarcoma dogs received chemotherapy following surgery (cisplatin q 28 days x 4). At completion of chemotherapy, dogs were randomized to receive L-MTP-PE or placebo. The L-MTP-PE group had a significantly longer median survival time compared to the placebo group (p < 0.021). Dogs with splenic hemangiosarcoma received combination chemotherapy following surgery (doxorubicin and cyclophosphamide q 21 days x 4). At the first chemotherapy, dogs were randomized to receive L-MTP-PE or placebo. The L-MTP-PE group had a significantly longer median survival time compared to the placebo group (p < 0.03). These studies show that L-MTP-PE is an effective agent for treatment of metastasis and can be safely administered in combination with chemotherapy.
authors.affiliation: Department of Medical Sciences, University of Wisconsin, Madison 53706.
authors.forename: E G
authors.initials: EG
authors.lastname: MacEwen
authors.forename: I D
authors.initials: ID
authors.lastname: Kurzman
authors.forename: S
authors.initials: S
authors.lastname: Helfand
authors.forename: D
authors.initials: D
authors.lastname: Vail
authors.forename: C
authors.initials: C
authors.lastname: London
authors.forename: W
authors.initials: W
authors.lastname: Kisseberth
authors.forename: R C
authors.initials: RC
authors.lastname: Rosenthal
authors.forename: L E
authors.initials: LE
authors.lastname: Fox
authors.forename: E T
authors.initials: ET
authors.lastname: Keller
authors.forename: J
authors.initials: J
authors.lastname: Obradovich
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000662:veterinary*; D002945:Cisplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy* / Q000601:surgery; D004285:Dogs; D004317:Doxorubicin / Q000627:therapeutic use; D006394:Hemangiosarcoma / Q000188:drug therapy / Q000601:surgery / Q000662:veterinary*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary / Q000662:veterinary*; D012516:Osteosarcoma / Q000188:drug therapy / Q000601:surgery / Q000662:veterinary*; D010714:Phosphatidylethanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D013160:Splenic Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000662:veterinary*
chemical_list: D000970:Antineoplastic Agents; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin