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Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic hemangiosarcoma in the dog: a randomized multi-institutional clinical trial.
|Title||Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic hemangiosarcoma in the dog: a randomized multi-institutional clinical trial.|
|Publication Type||Journal Article|
|Year of Publication||1995|
|Authors||Vail DM, MacEwen EG, Kurzman ID, Dubielzig RR, Helfand SC, Kisseberth WC, London CA, Obradovich JE, Madewell BR, Rodriguez CO|
|Journal||Clinical cancer research : an official journal of the American Association for Cancer Research|
|Date Published||1995 Oct|
|Keywords||Acetylmuramyl-Alanyl-Isoglutamine, Adjuvants, Immunologic, Animals, Antineoplastic Agents, Disease-Free Survival, Dog Diseases, Dogs, Drug Carriers, Female, Hemangiosarcoma, Interleukin-6, Liposomes, Male, Phosphatidylethanolamines, Splenic Neoplasms, Time Factors, Tumor Necrosis Factor-alpha|
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.
|Alternate Journal||Clin. Cancer Res.|