Incidence and risk factors associated with development of clinical cardiotoxicity in dogs receiving doxorubicin.

BACKGROUND: Doxorubicin (DOX) can cause cumulative cardiotoxicity in dogs, but the incidence of clinical cardiotoxicity in dogs receiving DOX has not been determined. HYPOTHESIS/OBJECTIVES: To determine if the duration of DOX infusion influences the incidence of cardiotoxicity, to characterize the incidence of clinical cardiotoxicity in dogs during or after DOX chemotherapy, and to identify any risk factors associated with cardiotoxicity. ANIMALS: Four-hundred ninety-four dogs that received at least 1 dose of DOX for the treatment of cancer. METHODS: Retrospective study of dogs that received DOX from 2006 to 2015. RESULTS: Of 494 dogs, 20 (4.0%) developed clinical cardiotoxicity. The duration of DOX infusion was not significantly associated with clinical cardiotoxicity, whereas a higher cumulative dose of DOX, higher body weight, decreases in fractional shortening after 5 doses of DOX, and development of ventricular premature contractions were significantly associated with clinical cardiotoxicity. High-risk breeds for developing dilated cardiomyopathy had an incidence of 15.4%, whereas low-risk breeds had an incidence of 3.0%. CONCLUSIONS AND CLINICAL IMPORTANCE: Although the duration of DOX infusion did not influence the incidence of cardiotoxicity, premature contractions and decreases in fractional shortening should raise concern for the development of clinical cardiotoxicity. Overall, the incidence of clinical DOX-induced cardiotoxicity is low, but Boxers and other breeds at high risk for dilated cardiomyopathy may be at an increased risk.

The impact of carboplatin and toceranib phosphate on serum vascular endothelial growth factor (VEGF) and metalloproteinase-9 (MMP-9) levels and survival in canine osteosarcoma.

In this pilot study, 10 dogs with osteosarcoma (OSA) were treated with amputation and subsequent carboplatin chemotherapy (300 mg/m2 IV q3wk × 4 doses) followed by toceranib phosphate (2.75 mg/kg PO q48h starting at day 14 post carboplatin). Monthly clinical monitoring and serum measurements of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were acquired. No dogs were removed from the study due to toxicity. Levels of VEGF and MMP-9 did not change over time. Seven dogs died related to local recurrence and/or pulmonary or bone metastasis and the remainder died of other causes. Median OSA-free survival was 238 d with 34% 1-year progression-free survival. Median overall survival was 253 d with 30% alive at 1.5 y and 10% alive at 2 y. Although this regimen was well-tolerated, survival times did not exceed previously published data from dogs treated with amputation plus chemotherapy alone.

Dans cette étude pilote, 10 chiens avec un ostéosarcome (OSA) ont été traités par amputation et chimiothérapie subséquente avec du carboplatin (300 mg/m2 IV q3sem × 4 doses) suivi de phosphate de toceranib (2,75 mg/kg PO q48h débutant au jour 14 suivant le carboplatin). Un suivi clinique mensuel et une mesure des taux sériques du facteur de croissance de l'endothélium vasculaire (FCEV) et de la matrice de la métalloprotéinase-9 (MMP-9) ont été obtenus. Aucun chien ne fut retiré de l'étude pour cause de toxicité. Les niveaux de FCEV et MMP-9 n'ont pas changé dans le temps. Sept chiens sont décédés dues à une rechute locale et/ou des métastases osseuses et les autres sont morts d'autres causes. La durée médiane de survie libre d'OSA était de 238 j avec 34 % de survie sans progression de la condition après 1 an. La durée de survie médiane était de 253 j avec 30 % en vie après 1,5 an et 10 % en vie après 2 ans. Bien que ce traitement ait été bien toléré, les temps de survie n'ont pas excédé les résultats publiés antérieurement pour des chiens traités par amputation et chimiothérapie uniquement.(Traduit par Docteur Serge Messier).