Phase I evaluation of doxorubicin and whole-body hyperthermia in dogs with lymphoma.
Fifteen previously untreated dogs with histologically confirmed, high-grade multicentric lymphoma were entered into a phase I study to evaluate combined doxorubicin and whole-body hyperthermia (DOX/WBH). Groups of three, four, and eight dogs were treated with whole-body hyperthermia and concurrent doxorubicin at 12 mg/m2, 24 mg/m2 and 30 mg/m2, respectively, after one doxorubicin induction dose at 30 mg/m2. Plateau temperature (42 +/- 0.1 degree C) was maintained for 90 minutes using a radiant heating device. A total of five DOX/WBH treatments per dog were planned, and these were given every 21 days. Treatment-related toxicity was not seen in the 12-mg/m2 doxorubicin dose group. Tumor progression prohibited administration of more than three DOX/WBH treatments to any dog in the 12-mg/m2 group. Premature ventricular contractions developed after the fifth treatment in one of the four dogs treated with 24 mg/m2 of doxorubicin. Two dogs (25%) in the 30-mg/m2 dose group had treatment-related toxicity. One dog experienced acute serious myelosuppression 1 week after the third treatment. This dog received all planned DOX/WBH treatments. Asymptomatic cardiac toxicosis consisting of decreased ejection fraction and fractional shortening developed in the second dog. This dog received only two DOX/WBH treatments. The three dogs treated at 12 mg/m2 had partial responses of short duration (60-83 days). Four dogs treated at 24 mg/m2 had complete responses for 150, 164, 186, and 200 days. Eight dogs treated at 30 mg/m2 had complete responses with a mean and median duration of 241 and 190 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Novotney
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CA
College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
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R L
RL
Macy
D W
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Dewhirst
M W
MW
Ogilvie
G K
GK
Withrow
S J
SJ
McEntee
M C
MC
Heidner
G L
GL
Allen
S A
SA
Thrall
D E
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D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D004283:Dog Diseases / Q000628:therapy*; D004285:Dogs; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D004341:Drug Evaluation; D005260:Female; D006321:Heart / Q000187:drug effects; D006979:Hyperthermia, Induced / Q000662:veterinary*; D008223:Lymphoma / Q000628:therapy / Q000662:veterinary*; D008297:Male; D016896:Treatment Outcome
D004317:Doxorubicin