Current studies of liposome muramyl tripeptide (CGP 19835A lipid) therapy for metastasis in spontaneous tumors: a progress review.
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.
MacEwen
E G
EG
Department of Medical Sciences, University of Wisconsin, Madison 53706.
Kurzman
I D
ID
Helfand
S
S
Vail
D
D
London
C
C
Kisseberth
W
W
Rosenthal
R C
RC
Fox
L E
LE
Keller
E T
ET
Obradovich
J
J
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*
D000970:Antineoplastic Agents; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin