Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic hemangiosarcoma in the dog

A randomized multi-institutional clinical trial

David M. Vail, E. Gregory MacEwen, Ilene D. Kurzman, Richard R. Dubielzig, Stuart C. Helfand, William C. Kisseberth, Cheryl A. London, Joyce E. Obradovich, Bruce R. Madewell, Carlos O. Rodriguez, Janean Fidel, Steven Susaneck, Mona Rosenberg

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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-α 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-α (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 chemoimmnnotherapy.

Original languageEnglish (US)
Pages (from-to)1165-1170
Number of pages6
JournalClinical Cancer Research
Volume1
Issue number10
StatePublished - Oct 1995

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Hemangiosarcoma
Liposomes
Immunotherapy
Clinical Trials
Dogs
Disease-Free Survival
Placebos
Splenectomy
mifamurtide
Canidae
Interleukin-6
Tumor Necrosis Factor-alpha
Neoplasm Metastasis
Drug Therapy
Serum
Doxorubicin
Cyclophosphamide
Animal Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Vail, D. M., MacEwen, E. G., Kurzman, I. D., Dubielzig, R. R., Helfand, S. C., Kisseberth, W. C., ... Rosenberg, M. (1995). Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic hemangiosarcoma in the dog: A randomized multi-institutional clinical trial. Clinical Cancer Research, 1(10), 1165-1170.

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic hemangiosarcoma in the dog : A randomized multi-institutional clinical trial. / Vail, David M.; MacEwen, E. Gregory; Kurzman, Ilene D.; Dubielzig, Richard R.; Helfand, Stuart C.; Kisseberth, William C.; London, Cheryl A.; Obradovich, Joyce E.; Madewell, Bruce R.; Rodriguez, Carlos O.; Fidel, Janean; Susaneck, Steven; Rosenberg, Mona.

In: Clinical Cancer Research, Vol. 1, No. 10, 10.1995, p. 1165-1170.

Research output: Contribution to journalArticle

Vail, DM, MacEwen, EG, Kurzman, ID, Dubielzig, RR, Helfand, SC, Kisseberth, WC, London, CA, Obradovich, JE, Madewell, BR, Rodriguez, CO, Fidel, J, Susaneck, S & Rosenberg, M 1995, 'Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic hemangiosarcoma in the dog: A randomized multi-institutional clinical trial', Clinical Cancer Research, vol. 1, no. 10, pp. 1165-1170.
Vail, David M. ; MacEwen, E. Gregory ; Kurzman, Ilene D. ; Dubielzig, Richard R. ; Helfand, Stuart C. ; Kisseberth, William C. ; London, Cheryl A. ; Obradovich, Joyce E. ; Madewell, Bruce R. ; Rodriguez, Carlos O. ; Fidel, Janean ; Susaneck, Steven ; Rosenberg, Mona. / Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic hemangiosarcoma in the dog : A randomized multi-institutional clinical trial. In: Clinical Cancer Research. 1995 ; Vol. 1, No. 10. pp. 1165-1170.
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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-α 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-α (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 chemoimmnnotherapy.",
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