Phase I Evaluation of Doxorubicin and Whole‐body Hyperthermia in Dogs with Lymphoma

Abstract

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 ± 0.1d̀C) 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 1week 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. It was concluded that after a single induction doxorubicin treatment at 30 mg/m2, five additional doses of doxorubicin at 30 mg/m2 can be administered without serious toxicity under hyperthermic conditions. Thus, there is no requisite doxorubicin dose reduction under hyperthermic conditions in comparison to the amount of doxorubicin normally given to dogs. Prospective evaluation of the efficacy of combined doxorubicin (at 30 mg/m2) and whole‐body hyperthermia compared with doxorubicin alone in dogs with lymphoma is warranted. (Journal of Veterinary Internal Medicine 1992; 6:245–249) Copyright © 1992, Wiley Blackwell. All rights reserved