Abstract
Background: Doxorubicin (DOX) is one of the most effective chemotherapeutics for canine high-grade lymphoma. In addition to dose-dependent chronic cardiotoxicity, DOX can trigger acute cardiac arrhythmias during drug infusion. Diphenhydramine premedication is commonly used, as histamine release is a proposed mechanism for DOX-associated arrhythmogenesis.Hypothesis/Objectives: The study objectives were to evaluate the incidence and severity of DOX infusion-related cardiac arrhythmias in dogs with high-grade lymphoma and evaluate the effect of diphenhydramine premedication on arrhythmia frequency and severity during and after DOX infusion.Animals: Twenty-two client-owned dogs with cytologically/histopathologically confirmed high-grade lymphoma were recruited, of which 19 were enrolled and 9 completed the study.Methods: Dogs were screened by echocardiogram and concurrent electrocardiogram for this randomized prospective crossover study. Group A received no premedication for DOX #1 and was premedicated with diphenhydramine for DOX #2; Group B received diphenhydramine with DOX #1 and no premedication for DOX #2. For both visits, Holter monitor data were collected for 1 h pre-DOX and 3 h post-DOX administration.Results: Nineteen dogs were enrolled and 9 dogs [Group A (5), Group B (4)] completed the protocol. There was no statistical difference between the DOX alone and DOX + diphenhydramine when evaluating the total number of ventricular premature complexes (VPCs, P = 0.34), change in VPCs/hour (P = 0.25), total number of atrial premature complexes (APCs, P = 0.5), change in APCs/hour (P = 0.06), or ventricular arrhythmia severity score (P > 0.99).Conclusions and clinical importance: This study demonstrates that in these dogs with rigorous pretreatment cardiovascular screening, DOX infusion did not induce significant arrhythmias. Furthermore, these data suggest that, with this screening approach, diphenhydramine may not alter the arrhythmia number or severity in canine DOX recipients.
Highlights
Doxorubicin (DOX) is one of the most widely used antineoplastic drugs in veterinary and human medicine and demonstrates efficacy against a variety of cancers such as lymphoma and solid tumors like hemangiosarcoma [1,2,3,4,5,6]
Three dogs failed screening with the identification of a significant ventricular arrhythmia in one dog, a heart base mass along with Ventricular Premature Complex (VPC) in one dog, and VPCs due to arrhythmogenic right ventricular cardiomyopathy in one dog
Based on the World Health Organization criteria for lymphoma, most dogs were considered at least a stage III [9], with three stage IV, five stage V, and two dogs with mediastinal lymphoma; not all dogs were fully staged as this was at the discretion of the pet owner and the clinician [58]
Summary
Doxorubicin (DOX) is one of the most widely used antineoplastic drugs in veterinary and human medicine and demonstrates efficacy against a variety of cancers such as lymphoma and solid tumors like hemangiosarcoma [1,2,3,4,5,6]. The most important chronic effect is a dosedependent and irreversible cardiomyopathy [20, 21] This can lead to congestive heart failure and ventricular arrhythmias, and is commonly associated with a poor prognosis, especially in canine patients [22,23,24,25,26]. Acute cardiotoxicities are associated with the peak level of DOX and/or rapid infusion [28, 33, 37] These effects vary from non-specific electrocardiogram ST changes to atrial and ventricular arrhythmias [38,39,40,41]. In addition to dose-dependent chronic cardiotoxicity, DOX can trigger acute cardiac arrhythmias during drug infusion. Hypothesis/Objectives: The study objectives were to evaluate the incidence and severity of DOX infusion-related cardiac arrhythmias in dogs with high-grade lymphoma and evaluate the effect of diphenhydramine premedication on arrhythmia frequency and severity during and after DOX infusion.
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