Dexrazoxane treatment of doxorubicin extravasation injury in four dogs

Venable, Rachel O.; Saba, Corey; Endicott, M. M.; Northrup, Nicole C.

doi:10.2460/javma.240.3.304

Cited by 21 publications

(8 citation statements)

References 24 publications

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“…Apoptosis induction by iron chelators or by anthracylines is covered elsewhere in this issue of the journal. Necrosis induction by iron dual inhibitors has been poorly defined, although it has been documented as one of the cellular responses to iron overloading, iron chelation, and in response to doxorubicin (260,268). The remaining part of this section will focus on cell cycle arrest and autophagy.…”

Section: Cellular Responses To Dual Inhibitionmentioning

confidence: 99%

Iron Chelators with Topoisomerase-Inhibitory Activity and Their Anticancer Applications

Rao

2013

Antioxidants & Redox Signaling

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Significance: Iron and topoisomerases are abundant and essential cellular components. Iron is required for several key processes such as DNA synthesis, mitochondrial electron transport, synthesis of heme, and as a co-factor for many redox enzymes. Topoisomerases serve as critical enzymes that resolve topological problems during DNA synthesis, transcription, and repair. Neoplastic cells have higher uptake and utilization of iron, as well as elevated levels of topoisomerase family members. Separately, the chelation of iron and the cytotoxic inhibition of topoisomerase have yielded potent anticancer agents. Recent Advances: The chemotherapeutic drugs doxorubicin and dexrazoxane both chelate iron and target topoisomerase 2 alpha (top2a). Newer chelators such as di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone and thiosemicarbazone -24 have recently been identified as top2a inhibitors. The growing list of agents that appear to chelate iron and inhibit topoisomerases prompts the question of whether and how these two distinct mechanisms might interplay for a cytotoxic chemotherapeutic outcome. Critical Issues: While iron chelation and topoisomerase inhibition each represent mechanistically advantageous anticancer therapeutic strategies, dual targeting agents present an attractive multi-modal opportunity for enhanced anticancer tumor killing and overcoming drug resistance. The commonalities and caveats of dual inhibition are presented in this review. Future Directions: Gaps in knowledge, relevant biomarkers, and strategies for future in vivo studies with dual inhibitors are discussed. Antioxid. Redox Signal. 18, 930-955.

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Section: Cellular Responses To Dual Inhibitionmentioning

confidence: 99%

Iron Chelators with Topoisomerase-Inhibitory Activity and Their Anticancer Applications

Rao

2013

Antioxidants & Redox Signaling

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“…Doxorubicin (DOX) is an anthracycline antitumor antibiotic used to treat many malignancies in dogs and people, including lymphoma, osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, and carcinomas . Repeated doses of DOX can result in potentially life‐threatening cardiotoxicity in both species . Clinical findings of cardiotoxicity include arrhythmias and decreased systolic function, resulting in a disease resembling dilated cardiomyopathy (DCM).…”

Section: Introductionmentioning

confidence: 99%

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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“…One dog developed one grade 3 phlebitis with skin and subcutaneous necrosis which required a surgical intervention. Severe tissue ulceration and necrosis has been described with doxorubicin and bisphosphonate extravasation in dogs [29,30]. Here, no injection site events were reported during the 12b80 administration, and no perivascular necrosis was observed.…”

Section: Discussionmentioning

confidence: 54%

Phase I dose escalation study of 12b80 (hydroxybisphosphonate linked doxorubicin) in naturally occurring osteosarcoma

et al. 2020

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Dexrazoxane treatment of doxorubicin extravasation injury in four dogs

Cited by 21 publications

References 24 publications

Iron Chelators with Topoisomerase-Inhibitory Activity and Their Anticancer Applications

Iron Chelators with Topoisomerase-Inhibitory Activity and Their Anticancer Applications

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

Phase I dose escalation study of 12b80 (hydroxybisphosphonate linked doxorubicin) in naturally occurring osteosarcoma

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