Preclinical study of sequential tumor necrosis factor and interleukin 2 in the treatment of spontaneous canine neoplasms

Recombinant human tumor necrosis factor and recombinant human interleukin 2 were administered in a sequential schedule to 30 dogs with a variety of spontaneous neoplasms. Dose escalation of both drugs was performed, and a maximally tolerated dose of recombinant human tumor necrosis factor of 125 mg/...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1991, Vol.51 (1), p.233-238
Main Authors: MOORE, A. S, THEILEN, G. H, NEWELL, A. D, MADEWELL, B. R, RUDOLF, A. R
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - veterinary
Dog Diseases - drug therapy
Dogs
Drug Administration Schedule
Female
Hematopoiesis - drug effects
Immunotherapy
Interleukin-2 - administration & dosage
Interleukin-2 - adverse effects
Lymphoma - drug therapy
Lymphoma - veterinary
Male
Mammary Neoplasms, Experimental - drug therapy
Mast-Cell Sarcoma - drug therapy
Mast-Cell Sarcoma - veterinary
Medical sciences
Melanoma - drug therapy
Melanoma - veterinary
Neoplasms - drug therapy
Neoplasms - veterinary
Pharmacology. Drug treatments
Recombinant Proteins - administration & dosage
Tumor Necrosis Factor-alpha - administration & dosage
Tumor Necrosis Factor-alpha - adverse effects
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Summary:Recombinant human tumor necrosis factor and recombinant human interleukin 2 were administered in a sequential schedule to 30 dogs with a variety of spontaneous neoplasms. Dose escalation of both drugs was performed, and a maximally tolerated dose of recombinant human tumor necrosis factor of 125 mg/m2 i.v. for 3 days, followed by 1.5 x 10(6) units/m2 of recombinant human interleukin 2 s.c. for 9 days, was derived. Dose-limiting toxicities were primarily gastrointestinal; however, weakness and malaise were seen during therapy at doses higher than the maximally tolerated dose. No clinically significant hematological toxicities were seen at any dose level. Objective tumor responses were seen in dogs with oral mucosal melanoma and cutaneous mastocytoma. Because of the histological, behavioral, and epidemiological similarities between human and canine tumor types, the canine cancer patient provides a unique model for the preclinical evaluation of recombinant cytokine therapy.
ISSN:0008-5472
1538-7445