Introduction

Cardiotoxicity limits the use of doxorubicin chemotherapy in dogs, often occurring after treatment is complete. No test can predict which dogs might, or will, develop cardiomyopathy. Cardiac troponin I (cTnI) increases in people after cardiotoxic chemotherapy, and peak concentrations occur within hours of treatment, subsequently returning to baseline; peak concentrations correlate with cardiac outcome. We hypothesized that cTnI would peak within 6 hours of doxorubicin administration in dogs, and that changes would be seen in global longitudinal myocardial strain. Our goal was to identify the time point at which possible predictors of cardiotoxicity should be studied.

Methods

This prospective, single-arm trial enrolled dogs greater than 10 kg scheduled to receive single-agent doxorubicin at every two-week intervals. End-of-infusion serum concentration (Cmax) of doxorubicin and doxorubicinol were assessed using high performance liquid chromatography—tandem mass spectrometry at each treatment to correlate cardiac findings with pharmacokinetics. cTnI (ultrasensitive assay), electrocardiography, and echocardiographic measures of myocardial strain and systolic function, were collected at 0, 2, 4, and 6 hours after each infusion. Cardiac function was monitored monthly for 4 months after doxorubicin completion.

Results

Dogs enrolled received 5 (n=7), 4 (n=1), or 1 (n=2) dose(s) of doxorubicin. Diagnoses included lymphoma (n=8) and solid tumors (hemangiosarcoma, n=2). Intra- and interpatient doxorubicin Cmax varied with no consistent pattern. cTnI and cardiac analyses are in progress. Doxorubicin Cmax, doxorubicinol, and echo values will be correlated with cTnI concentrations. Though not anticipated given the small number of dogs enrolled, two dogs did develop cardiac complications possibly attributable to doxorubicin.

Conclusion

Pending.

Funding Information

This clinical study was funded by a resident grant from the American College of Veterinary Internal Medicine.