Phase I Dose Escalation of Doxorubicin Chemotherapy in Tumor-Bearing Equidae

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Abstract

Background:

There is no information on the use of doxorubicin in horses with tumors.

Objective:

To determine dose-limiting toxicosis (DLT) and maximum tolerated dose (MTD) of doxorubicin in tumor-bearing horses.

Animals:

Seventeen horses with 34 localized or multicentric advanced tumors.

Methods:

Two-stage dose-ranging design involving intrapatient and interpatient dose escalation. Treatment protocol included 6 treatment cycles given at 3-week intervals with dosages ranging from 40 to 85 mg/m2. Clinical signs, hematologic, and nonhematologic changes were evaluated.

Results:

Total doses ranged from 1,127 to 2,900 mg in 12 horses that completed the assigned treatment protocols. The MTD was 75 mg/m2. Hypersensitivity reactions and neutropenia were dose limiting. Hypersensitivity was dose-dependent but schedule invariant. Neutropenia was dose- and cycle-dependent but dose-escalation schedule invariant. Cardiotoxicity was not observed.

Conclusion and Clinical Relevance:

The recommended dosage of doxorubicin to treat horses is 70 mg/m2 given at 3-week intervals as single agent. Adjunctive treatment with antihistamines and nonsteroidal anti-inflammatory drugs is recommended to control hypersensitivity.

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