The current and future role of dexrazoxane as a cardioprotectant in anthracycline treatment: expert�panel�review

Swain, Sandra M.; Vici, Patrizia

doi:10.1007/s00432-003-0498-7

Cited by 140 publications

(84 citation statements)

References 31 publications

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“…85 Dexrazoxane consistently reduces the cardiotoxic effects of anthracyclines, allowing higher anthracycline doses to be used safely. 86 Complete protection, however, could not be achieved in most of the studies, and it is not known yet whether dexrazoxane provides any protection against late cardiovascular effects. Importantly, the weight of evidence shows that dexrazoxane does not affect the antitumor activity of anthracyclines.…”

Section: Previous Anthracycline Exposurementioning

confidence: 99%

“…Importantly, the weight of evidence shows that dexrazoxane does not affect the antitumor activity of anthracyclines. 86 Another strategy is the development of liposomal drug formulations of the anthracyclines. Liposomal encapsulation alters the tissue distribution of anthracyclines: tissues with a sinusoidal capillary system preferentially take up liposomes, so the continuous capillaries of cardiac muscles would reduce heart exposure to the drug.…”

Section: Previous Anthracycline Exposurementioning

confidence: 99%

“…Thorough pre-HD chemotherapy cardiologic evaluation including 2D echo 28,88 History of anthracycline exposure Thorough pre-HD chemotherapy cardiologic evaluation including 2D echo restriction of total anthracycline exposure to o400 mg/m 2 use of cardioprotectors (ie dexrazoxane) use of liposomal formulations of anthracyclines 22,78,80,[84][85][86][87] Older High-dose therapy cardiac toxicity P Morandi et al months. 103 Finally, in 11 patients whose pre-transplant LVEF was o50%, no signs of heart failure were recorded at prolonged follow-up after HSC transplantation.…”

Section: Dosagementioning

confidence: 99%

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Cardiac toxicity of high-dose chemotherapy

Morandi

Ruffini

Benvenuto

et al. 2004

Bone Marrow Transplant

148

104

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Summary:Cardiac toxicity is an uncommon but potentially serious complication of high-dose (HD) chemotherapy and little is known about incidence, severity and underlying mechanisms. We have systematically reviewed the literature of the last 30 years to summarize and appraise the published evidence on cardiac toxicity associated with HD chemotherapy. HD cyclophosphamide-containing regimens have been most commonly associated with cardiac toxicity, with a progressively decreasing incidence over time. Dosage, application regimens and coadministration of other chemotherapeutic agents emerged as risk factors. While cardiac toxicity has been rarely associated with other cytotoxic drugs, an unexpected incidence of severe cardiotoxicity resulted from reduced-intensity conditioning regimens containing melphalan and fludarabine. Predictive value of cardiologic examination of patients is limited, and patients with a slight depression of cardiac performance could tolerate HD chemotherapy. Clinical examination, resting electrocardiography and dosage adjustment in overweight patients remain the mainstay of prevention, with bidimensional echocardiography (2D echo) for patients with a history of anthracycline exposure. Strategies to decrease the long-term negative impact of anthracycline administration on cardiac performance are being investigated. New 2D echo-based techniques and circulating markers of cardiac function hold promise for allowing identification of patients at high risk for and early diagnosis of cardiac toxicity.

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Section: Previous Anthracycline Exposurementioning

confidence: 99%

Section: Previous Anthracycline Exposurementioning

confidence: 99%

Section: Dosagementioning

confidence: 99%

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Cardiac toxicity of high-dose chemotherapy

Morandi

Ruffini

Benvenuto

et al. 2004

Bone Marrow Transplant

148

104

View full text Add to dashboard Cite

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“…The cytoprotective effects of dexrazoxane, in the presence of doxorubicin, have been well established in animal species (11) and hu- mans (12). Furthermore, clinical trials have revealed that the cytoprotection of dexrazoxane does not interfere with the anti-tumor effects of doxorubicin, and therefore to this day dexrazoxane serves as one of the best cytoprotective drugs against doxorubicin (13). The hydroxyl radical that makes up the ROS is a highly reactive species that can cause lipid peroxidation, oxidative damage to DNA, and eventual cell death (14).…”

Section: Cytoprotective Effects Of Dexrazoxane Losartan and Diltiazementioning

confidence: 99%

Cytoprotective potential of anti-ischemic drugs against chemotherapy-induced cardiotoxicity in H9c2 myoblast cell line

et al. 2013

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To investigate potential prevention or attenuation of anti- cancer drug induced cardiotoxicity using anti-ischemic drugs, a rat myoblast (H9c2) cell line was used as our in vitro cardiac model. Irinotecan and doxorubicin were found to be cytotoxic for the H9c2 cell line with IC50 of 30.69 ± 6.20 and 20.94 ± 6.05 mmol L-1, respectively. 5-Flurouracil and cladribine were not cytotoxic and thus IC50 could not be calculated. When 100 mmol L-1 doxorubicin was incubated for 72 hours with 50 mmol L-1 diltiazem, 100 mmol L-1 dexrazoxane and 100 mmol L-1 losartan, respectively, there was a 58.7 ± 10.2, 52.2 ± 11.7 and 44.7 ± 5.4 % reduction in cell death. When 200 mmol L-1 irinotecan was incubated for 72 hours with 100 mmol L-1 dexrazoxane, losartan and diltiazem, respectively, a 27.7 ± 6.9, 25.6 ± 5.1, and 19.1 ± 2.3 % reduction in cell death was observed. Our data suggests that losartan and diltiazem were as effective as dexrazoxane in protecting the cells against irinotecan- and doxorubicin-induced cell toxicity. These findings offer potential uses of anti- -ischemic drugs for ablation of cytotoxicity in response to mitochondrial injury, thereby improving patient outcomes and reducing health-care costs.

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“…Multiple other randomized trials and a pooled analysis have not confirmed these findings [7,12,17,[21][22][23][24]26]. However, these studies enrolled mainly patients with solid tumors; the majority of them are adults with advanced breast cancer.…”

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confidence: 96%