Open AccessPhase I Dose Escalation of Doxorubicin Chemotherapy in Tumor‐Bearing Equidae
Author(s) -
Théon A.P.,
Pusterla N.,
Magdesian K.G.,
Wilson W.D.
Publication year - 2013
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/jvim.12145
Subject(s) - medicine , neutropenia , dose , doxorubicin , chemotherapy , maximum tolerated dose , gastroenterology , pharmacology
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/m 2 . 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/m 2 . 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/m 2 given at 3‐week intervals as single agent. Adjunctive treatment with antihistamines and nonsteroidal anti‐inflammatory drugs is recommended to control hypersensitivity.