Value of Echocardiography and Electrocardiography as Screening Tools Prior to Doxorubicin Administration

Ratterree, William; Gieger, Tracy L.; Pariaut, Romain; Saelinger, Carley; Strickland, Keith N.

doi:10.5326/jaaha-ms-5680

Cited by 18 publications

(14 citation statements)

References 20 publications

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“…The incidence of confirmed and suspected cardiotoxicity‐related deaths in this population of dogs was 2.0% (10/494), although only 0.6% (3/494) could be confirmed on necropsy. The MST for patients after developing clinical signs in our study (29 days) was similar to the previously reported result of 26.5 days . Other reported survival times include 48 hours and 90 days …”

Section: Discussionsupporting

confidence: 91%

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

Hallman

Hauck

Williams

et al. 2019

Veterinary Internal Medicne

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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.

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Section: Discussionsupporting

confidence: 91%

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

Hallman

Hauck

Williams

et al. 2019

Veterinary Internal Medicne

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“…No specific cardiac monitoring was performed unless dictated by changes (such as new murmur, arrhythmia) noted on physical examination. As our protocol would result in cumulative doses of less than 180 mg m −2 , and previous evidence has demonstrated that routine echocardiogram or electrocardiogram (ECG) monitoring is insensitive for detection of DOX‐induced cardiotoxicity in non‐symptomatic patients, this was not deemed necessary for patient assessment . Physical examination and CBC were also performed by clinicians at the UW‐VMTH or the referring veterinarian 1 week following each DOX dose.…”

Section: Methodsmentioning

confidence: 99%

Safety evaluation of combination doxorubicin and toceranib phosphate (Palladia®) in tumour bearing dogs: a phase I dose‐finding study

Pellin

Wouda

Robinson

et al. 2016

Vet Comparative Oncology

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Combination chemotherapy holds promise for improving outcomes in malignancy when compared with single-agent approaches. Care must be taken to avoid overlapping toxicity and to utilize agents with differing mechanisms of action. A phase I dose-finding trial was performed to determine the maximally tolerated dose (MTD) of a concurrent toceranib and doxorubicin (DOX) combination protocol where toceranib dose was maintained at or near 2.75 mg kg by mouth every other day (PO EOD) while escalating DOX dosage. The dose-limiting toxicity was found to be neutropenia and the MTD of the combination was determined to be 25 mg m of DOX q 21 days given concurrently with toceranib 2.75 mg kg PO EOD. This combination was well tolerated with no excessive gastrointestinal toxicity nor novel adverse events (AEs) noted. Anti-tumour activity was observed in the majority of cases. This combination warrants further investigation in the context of phase II/III clinical trials to characterize efficacy and long-term AE profiles.

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“…In one of the largest studies in dogs reporting on the use of doxorubicin for the treatment of osteosarcoma, 8% developed heart disease [22]. In another recent study of 94 dogs with various neoplasms treated with doxorubicin, the incidence of cardiotoxicity was 8% [38]. The dog in our study that developed congestive heart failure was an Irish Wolfhound and the cardiac failure was clinically diagnosed after a cumulative dose of 90 mg/m 2 of doxorubicin.…”

Section: Discussionmentioning

confidence: 62%

Pharmacokinetic study and evaluation of the safety of taurolidine for dogs with osteosarcoma

Marley

Helfand

Simpson

et al. 2013

J Exp Clin Cancer Res

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BackgroundOsteosarcoma in dogs and humans share many similarities and the dog has been described as an excellent model to study this disease. The median survival in dogs has not improved in the last 25 years. Taurolidine has been shown to be cytotoxic to canine and human osteosarcoma in vitro. The goals of this study were to determine the pharmacokinetics and safety of taurolidine in healthy dogs and the safety of taurolidine in combination with doxorubicin or carboplatin in dogs with osteosarcoma.MethodsTwo percent taurolidine was infused into six healthy dogs (150 mg/kg) over a period of two hours and blood samples were taken periodically. One dog received taurolidine with polyvinylpyrrolidone (PVP) as its carrier and later received PVP-free taurolidine as did all other dogs in this study. Serum taurolidine concentrations were determined using high-performance liquid chromatography (HPLC) online coupled to ESI-MS/MS in the multiple reaction monitoring mode. Subsequently, the same dose of taurolidine was infused to seven dogs with osteosarcoma also treated with doxorubicin or carboplatin.ResultsTaurolidine infusion was safe in 6 healthy dogs and there were no significant side effects. Maximum taurolidine serum concentrations ranged between 229 to 646 μM. The dog that received taurolidine with PVP had an immediate allergic reaction but recovered fully after the infusion was stopped. Three additional dogs with osteosarcoma received doxorubicin and taurolidine without PVP. Toxicities included dilated cardiomyopathy, protein-losing nephropathy, renal insufficiency and vasculopathy at the injection site. One dog was switched to carboplatin instead of doxorubicin and an additional 4 dogs with osteosarcoma received taurolidine-carboplatin combination. One incidence of ototoxicity occurred with the taurolidine- carboplatin combination. Bone marrow and gastro-intestinal toxicity did not appear increased with taurolidine over doxorubicin or carboplatin alone.ConclusionsTaurolidine did not substantially exacerbate bone marrow or gastro-intestinal toxicity however, it is possible that taurolidine increased other toxicities of doxorubicin and carboplatin. Administering taurolidine in combination with 30 mg/m2 doxorubicin in dogs is not recommended but taurolidine in combination with carboplatin (300 mg/m2) appears safe.

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Value of Echocardiography and Electrocardiography as Screening Tools Prior to Doxorubicin Administration

Cited by 18 publications

References 20 publications

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

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

Safety evaluation of combination doxorubicin and toceranib phosphate (Palladia®) in tumour bearing dogs: a phase I dose‐finding study

Pharmacokinetic study and evaluation of the safety of taurolidine for dogs with osteosarcoma

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