Adjuvant therapy for osteosarcoma in dogs

Results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin

Ilene D. Kurzman, E. Gregory MacEwen, Robert C. Rosenthal, Leslie E. Fox, Evan T. Keller, Stuart C. Helfand, David M. Vail, Richard R. Dubielzig, Bruce R. Madewell, Carlos O. Rodriguez, Joyce Obradovich, Janean Fidel, Mona Rosenberg

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Abstract

Two randomized, double-blind clinical trials in dogs with spontaneous appendicular osteosarcoma treated with combination chemoimmunotherapy are reported. In both trials, dogs without overt metastasis underwent complete amputation of the affected limb. In trial 1, 40 dogs were treated with cisplatin chemotherapy [(CDDP), 70 mg/m2 i.v. every 28 days x 4]. Following CDDP, dogs without evidence of overt metastasis (n = 25) were randomized to receive liposome-encapsulated muramyl tripeptide phosphatidylethanolamine [(L-MTP-PE), 2 mg/m2 i.v.) or placebo liposomes (lipid equivalent) twice weekly for 8 weeks. Of 14 dogs in the placebo group, 13 (93%) died of metastasis; the median survival time was 9.8 months. Of 11 dogs in the L-MTP-PE group, 8 (73%) developed metastasis; the median survival time was 14.4 months, which was significantly longer than that of the placebo group (P < 0.01). In trial 2, 64 dogs received CDDP (70 mg/m2 i.v. every 21 days x 4) and were randomized to concurrently receive L-MTP-PE (2 mg/m2 i.v.) twice or once weekly, or placebo liposomes once weekly for 8 weeks. Median survival times were 10.3, 10.5, and 7.6 months, respectively. There were no significant differences among the three treatment groups in trial 2. Survival times for dogs receiving L-MTP-PE in trial 1 were significantly longer than those for dogs in trial 2 that received four doses of CDDP concurrently with twice weekly L-MTP-PE (P < 0.04). The results of the first trial confirm our previous observation that L-MTP-PE has antimetastatic activity in dogs with osteosarcoma when given following amputation. The results of the second trial demonstrate that there is no survival advantage of administering L-MTP-PE concurrently with CDDP.

Original languageEnglish (US)
Pages (from-to)1595-1601
Number of pages7
JournalClinical Cancer Research
Volume1
Issue number12
StatePublished - Dec 1995

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Osteosarcoma
Liposomes
Cisplatin
Randomized Controlled Trials
Dogs
Placebos
Neoplasm Metastasis
Therapeutics
Amputation
mifamurtide
Extremities
Clinical Trials
Lipids
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kurzman, I. D., MacEwen, E. G., Rosenthal, R. C., Fox, L. E., Keller, E. T., Helfand, S. C., ... Rosenberg, M. (1995). Adjuvant therapy for osteosarcoma in dogs: Results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin. Clinical Cancer Research, 1(12), 1595-1601.

Adjuvant therapy for osteosarcoma in dogs : Results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin. / Kurzman, Ilene D.; MacEwen, E. Gregory; Rosenthal, Robert C.; Fox, Leslie E.; Keller, Evan T.; Helfand, Stuart C.; Vail, David M.; Dubielzig, Richard R.; Madewell, Bruce R.; Rodriguez, Carlos O.; Obradovich, Joyce; Fidel, Janean; Rosenberg, Mona.

In: Clinical Cancer Research, Vol. 1, No. 12, 12.1995, p. 1595-1601.

Research output: Contribution to journalArticle

Kurzman, ID, MacEwen, EG, Rosenthal, RC, Fox, LE, Keller, ET, Helfand, SC, Vail, DM, Dubielzig, RR, Madewell, BR, Rodriguez, CO, Obradovich, J, Fidel, J & Rosenberg, M 1995, 'Adjuvant therapy for osteosarcoma in dogs: Results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin', Clinical Cancer Research, vol. 1, no. 12, pp. 1595-1601.
Kurzman, Ilene D. ; MacEwen, E. Gregory ; Rosenthal, Robert C. ; Fox, Leslie E. ; Keller, Evan T. ; Helfand, Stuart C. ; Vail, David M. ; Dubielzig, Richard R. ; Madewell, Bruce R. ; Rodriguez, Carlos O. ; Obradovich, Joyce ; Fidel, Janean ; Rosenberg, Mona. / Adjuvant therapy for osteosarcoma in dogs : Results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin. In: Clinical Cancer Research. 1995 ; Vol. 1, No. 12. pp. 1595-1601.
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title = "Adjuvant therapy for osteosarcoma in dogs: Results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin",
abstract = "Two randomized, double-blind clinical trials in dogs with spontaneous appendicular osteosarcoma treated with combination chemoimmunotherapy are reported. In both trials, dogs without overt metastasis underwent complete amputation of the affected limb. In trial 1, 40 dogs were treated with cisplatin chemotherapy [(CDDP), 70 mg/m2 i.v. every 28 days x 4]. Following CDDP, dogs without evidence of overt metastasis (n = 25) were randomized to receive liposome-encapsulated muramyl tripeptide phosphatidylethanolamine [(L-MTP-PE), 2 mg/m2 i.v.) or placebo liposomes (lipid equivalent) twice weekly for 8 weeks. Of 14 dogs in the placebo group, 13 (93{\%}) died of metastasis; the median survival time was 9.8 months. Of 11 dogs in the L-MTP-PE group, 8 (73{\%}) developed metastasis; the median survival time was 14.4 months, which was significantly longer than that of the placebo group (P < 0.01). In trial 2, 64 dogs received CDDP (70 mg/m2 i.v. every 21 days x 4) and were randomized to concurrently receive L-MTP-PE (2 mg/m2 i.v.) twice or once weekly, or placebo liposomes once weekly for 8 weeks. Median survival times were 10.3, 10.5, and 7.6 months, respectively. There were no significant differences among the three treatment groups in trial 2. Survival times for dogs receiving L-MTP-PE in trial 1 were significantly longer than those for dogs in trial 2 that received four doses of CDDP concurrently with twice weekly L-MTP-PE (P < 0.04). The results of the first trial confirm our previous observation that L-MTP-PE has antimetastatic activity in dogs with osteosarcoma when given following amputation. The results of the second trial demonstrate that there is no survival advantage of administering L-MTP-PE concurrently with CDDP.",
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