Functional monitoring of anthracycline cardiotoxicity:a prospective, blinded, long-term observational study of outcome in 120 patients

Jensen, Benny Vittrup; Skovsgaard, Torben; Nielsen, Steen Levin

doi:10.1093/annonc/mdf132

Cited by 310 publications

(198 citation statements)

References 36 publications

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“…13 In a large retrospective analysis, Ryberg et al reported estimated CHF risks of 0.6% and 14.5% at cumulative doxorubicin doses of 550 mg/m 2 and 1000 mg/m 2 , respectively. 14 However, a long-term prospective trial 15 showed that patients who received high cumulative doses of epirubicin (850 -1000 mg/m 2 ) had a risk of CHF that increased over a 5-year period (11% at 1 year, 20% at 5 years). Liposomal anthracyclines seemed to have an improved cardiotoxicity profile in preclinical studies.…”

Section: Discussionmentioning

confidence: 99%

Congestive heart failure in patients treated with doxorubicin

Swain

Whaley²,

Ewer

2003

Cancer

1,984

1,256

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BACKGROUNDDoxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug. A large‐scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7% of patients developed doxorubicin‐related congestive heart failure (CHF) after a cumulative dose of 550 mg/m2. To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting, the authors evaluated data from three prospective studies to determine both the incidence of doxorubicin‐related CHF and the accumulated dose of doxorubicin at which CHF occurs.METHODSA group of 630 patients who were randomized to a doxorubicin‐plus‐placebo arm of three Phase III studies, two studies in patients with breast carcinoma and one study in patients with small cell lung carcinoma, were included in the analysis.RESULTSThirty‐two of 630 patients had a diagnosis of CHF. Analysis indicated that an estimated cumulative 26% of patients would experience doxorubicin‐related CHF at a cumulative dose of 550 mg/m2. Age appeared to be an important risk factor for doxorubicin‐related CHF after a cumulative dose of 400 mg/m2, with older patients (age > 65 years) showing a greater incidence of CHF compared with younger patients (age ≤ 65 years). In addition, > 50% of the patients who experienced doxorubicin‐related CHF had a reduction < 30% in left ventricular ejection fraction (LVEF) while they were on study.CONCLUSIONSDoxorubicin‐related CHF occurs with greater frequency and at a lower cumulative dose than previously reported. These findings further indicate that LVEF is not an accurate predictor of CHF in patients who receive doxorubicin. Cancer 2003;97:2869–79. © 2003 American Cancer Society.DOI 10.1002/cncr.11407

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Section: Discussionmentioning

confidence: 99%

Congestive heart failure in patients treated with doxorubicin

Swain

Whaley²,

Ewer

2003

Cancer

1,984

1,256

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“…Finally, an association of risk of CHF with age has been proposed for patients receiving anthracycline-based chemotherapy. 81,84,99 A summary of all suspected risk factors for HD chemotherapy-associated cardiac toxicity and relative preventive strategies is listed in Table 2.…”

Section: Radiation Treatmentmentioning

confidence: 99%

Cardiac toxicity of high-dose chemotherapy

Morandi

Ruffini

Benvenuto

et al. 2004

Bone Marrow Transplant

150

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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“…[7] Epirubicin-induced myocardial dysfunction detected early by serial tissue Doppler echocardiography has been correlated with oxidative stress markers with an unchanged LVEF during epirubicin chemotherapy. [8] DTI associated with SRI has shown its value in early detection of epirubicin-induced cardiotoxicity, and a measurable SR peak depression has been regarded as the earliest sign of left ventricular regional systolic dysfunction in epirubicintreated patients long before a clinical manifestation of heart failure.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Salidroside on Epirubicin-Induced Early Left Ventricular Regional Systolic Dysfunction in Patients with Breast Cancer

et al. 2012

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Background: Salidroside [2-(4-hydroxyphenyl)ethyl-b-D-glucopyranoside], one of the most potent ingredients extracted from the plant Rhodiola rosea L., has been shown to have a cardiovascular protective effect as an antioxidant, and early treatment of epirubicin-induced cardiotoxicity has been the focus of clinical chemotherapy in patients with breast cancer. However, the cardioprotective effects of salidroside on epirubicin-induced cardiotoxicity, especially early left ventricular regional systolic dysfunction, have to date been sparsely investigated. Objective: The aim of this study was to investigate the protective effects of salidroside in preventing early left ventricular regional systolic dysfunction induced by epirubicin. Methods: Sixty patients with histologically confirmed breast cancer were enrolled. Eligible patients were randomized to receive salidroside (600 mg/day; n = 30) or placebo (n = 30) starting 1 week before chemotherapy. Patients were investigated by means of echocardiography and strain rate (SR) imaging. We also measured plasma concentrations of reactive oxygen species (ROS). All parameters were assessed at baseline and 7 days after each new epirubicin dose of 100 mg/m 2 . Results: A decline of the SR peak was observed at an epirubicin dose of 200 mg/m 2 , with no significant differences between salidroside and placebo (1.35 -0.36 vs 1.42 -0.49/second). At growing cumulative doses of epirubicin, the SR normalized only with salidroside, showing a significant difference in comparison with placebo at epirubicin doses of 300 mg/m 2 (1.67 -0.43 vs 1.32 -0.53/second, p < 0.05) and 400 mg/m 2 (1.68 -0.29 vs 1.40 -0.23/second, p < 0.05). Moreover, a significant increase in plasma concentrations of ROS was found with placebo, but they remained unchanged with salidroside.

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Functional monitoring of anthracycline cardiotoxicity:a prospective, blinded, long-term observational study of outcome in 120 patients

Abstract: Due to the displaced cardiotoxic manifestation, functional monitoring in close connection with anthracycline administration appears to be a poorly effective method while later monitoring is essential. Current monitoring recommendations should therefore be revised.

Cited by 310 publications

References 36 publications

Congestive heart failure in patients treated with doxorubicin

Congestive heart failure in patients treated with doxorubicin

Cardiac toxicity of high-dose chemotherapy

Protective Effects of Salidroside on Epirubicin-Induced Early Left Ventricular Regional Systolic Dysfunction in Patients with Breast Cancer

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