title: Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic hemangiosarcoma in the dog: a randomized multi-institutional clinical trial.
abstract: Canine splenic hemangiosarcoma (HSA) is a spontaneous tumor with high metastatic potential. Despite surgical excision, most dogs die within 2 months of diagnosis as a result of widespread visceral metastasis. This study was designed to determine the efficacy of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) when used in combination with splenectomy and systemic chemotherapy for the treatment of HSA in the dog. Thirty-two dogs with HSA and without gross evidence of metastases were treated with splenectomy, stratified by clinical stage, and randomized to receive doxorubicin/cyclophosphamide chemotherapy and either L-MTP-PE immunotherapy or lipid equivalent (placebo liposomes). Dogs were subsequently followed to determine disease-free survival and overall survival times. The effects of L-MTP-PE on serum tumor necrosis factor-alpha and interleukin 6 activity were assessed on a small subset of dogs. Dogs receiving L-MTP-PE had significantly prolonged disease-free survival (P = 0.037) and overall survival (P = 0.029) compared with dogs receiving placebo. Dogs with clinical stage I disease had significantly prolonged disease-free survival (P = 0. 026) and overall survival (P = 0.017) compared with dogs with clinical stage II disease. Dogs receiving L-MTP-PE had significantly greater serum tumor necrosis factor-alpha (P < 0.001) and interleukin 6 (P = 0.007) activities compared with placebo-treated dogs. L-MTP-PE has significant antimetastatic activity in highly malignant, spontaneously occurring, splenic HSA in the dog. Canine HSA may have potential as a large animal model for additional investigation of antimetastatic chemoimmunotherapy.
authors.affiliation: Departments of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Vail
authors.forename: E G
authors.initials: EG
authors.lastname: MacEwen
authors.forename: I D
authors.initials: ID
authors.lastname: Kurzman
authors.forename: R R
authors.initials: RR
authors.lastname: Dubielzig
authors.forename: S C
authors.initials: SC
authors.lastname: Helfand
authors.forename: W C
authors.initials: WC
authors.lastname: Kisseberth
authors.forename: C A
authors.initials: CA
authors.lastname: London
authors.forename: J E
authors.initials: JE
authors.lastname: Obradovich
authors.forename: B R
authors.initials: BR
authors.lastname: Madewell
authors.forename: C O
authors.initials: CO
authors.lastname: Rodriguez
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004283:Dog Diseases / Q000097:blood / Q000188:drug therapy*; D004285:Dogs; D004337:Drug Carriers; D005260:Female; D006394:Hemangiosarcoma / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D015850:Interleukin-6 / Q000097:blood; D008081:Liposomes; D008297:Male; D010714:Phosphatidylethanolamines / Q000627:therapeutic use*; D013160:Splenic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D004337:Drug Carriers; D015850:Interleukin-6; D008081:Liposomes; D010714:Phosphatidylethanolamines; D014409:Tumor Necrosis Factor-alpha; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine