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/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.
Moore
A S
AS
Tufts University, School of Veterinary Medicine, North Grafton, Massachusetts 01536.
Theilen
G H
GH
Newell
A D
AD
Madewell
B R
BR
Rudolf
A R
AR
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000662:veterinary; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004334:Drug Administration Schedule; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008223:Lymphoma / Q000188:drug therapy / Q000662:veterinary; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D012515:Mast-Cell Sarcoma / Q000188:drug therapy / Q000662:veterinary; D008545:Melanoma / Q000188:drug therapy / Q000662:veterinary; D009369:Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D011994:Recombinant Proteins / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000009:adverse effects
D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha