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1 July 1996 | Volume 125 Issue 1 | Pages 47-58
Purpose: To review the current understanding of the clinical significance, detection, pathogenesis, and prevention of anthracycline-induced cardiotoxicity.
Data Sources: A MEDLINE search of the English-language medical literature and a manual search of the bibliographies of relevant articles, including abstracts from national cardiology meetings.
Study Selection: Pertinent clinical and experimental studies addressing the clinical relevance, pathogenesis, detection, and prevention of anthracycline cardiotoxicity were selected from peer-reviewed journals without judgments about study design. A total of 137 original studies and 9 other articles were chosen.
Data Extraction: Data quality and validity were assessed by each author independently. Statistical analysis of combined data was inappropriate given the differences in patient selection, testing, and follow-up in the available studies.
Data Synthesis: Anthracycline-induced cardiotoxicity limits effective cancer chemotherapy by causing early cardiomyopathy, and it can produce late-onset ventricular dysfunction years after treatment has ceased. Detection of subclinical anthracycline-induced cardiomyopathy through resting left ventricular ejection fraction or echocardiographic fractional shortening is suboptimal. Conventional doses of anthracycline often lead to permanent myocardial damage and reduced functional reserve. Underlying pathogenetic mechanisms may include free-radical-mediated myocyte damage, adrenergic dysfunction, intracellular calcium overload, and the release of cardiotoxic cytokines. Dexrazoxane is the only cardioprotectant clinically approved for use against anthracyclines, and it was only recently introduced for selected patients with breast cancer who are receiving anthracycline therapy.
Conclusions: A rapidly growing number of persons, including an alarming fraction of the 150 000 or more adults in the United States who have survived childhood cancer, will have substantial morbidity and mortality because of anthracycline-related cardiac disease. The development of effective protection against anthracycline-induced cardiotoxicity will probably have a significant effect on the overall survival of these patients.
Three distinct types of anthracycline-induced cardiotoxicity have been described. First, acute or subacute injury can occur immediately after treatment. This rare form of cardiotoxicity may cause transient arrhythmias [8, 9], a pericarditis-myocarditis syndrome, or acute failure of the left ventricle [10]. Second, anthracyclines can induce chronic cardiotoxicity resulting in cardiomyopathy. This a more common form of damage and is clinically the most important [11-13]. Finally, late-onset anthracycline cardiotoxicity causing late-onset ventricular dysfunction [14-16] and arrhythmias [17-19], which manifest years to decades after anthracycline treatment has been completed, is increasingly recognized.
Chronic anthracycline-induced cardiomyopathy characteristically presents within 1 year of treatment. In a series of more than 3900 patients treated with anthracycline, Von Hoff and associates [6] noted that congestive heart failure secondary to anthracycline-induced chronic cardiomyopathy occurred 0 to 231 days after the completion of anthracycline therapy. In contrast, late-onset anthracycline-induced cardiac abnormalities have been reported to occur much later, after a prolonged asymptomatic period [14-16]. Other cardiovascular risk factors predisposing to heart failure, such as occult hypertension and subclinical coronary artery disease, may have confounded interpretation of the exact contribution made by anthracyclines in these studies. However, anthracyclines are clearly an important independent risk factor leading to both early and delayed congestive heart failure in survivors of cancer. There is no universally defined point after the onset of chronic cardiomyopathy at which late-onset cardiac abnormalities appear. For the purposes of this review, we broadly define "chronic cardiotoxicity" as cardiotoxicity occurring within 1 year of treatment and "late-onset cardiotoxicity" as cardiotoxicity occurring more than 1 year after the completion of anthracycline therapy.
Acute and subacute cardiac toxicity, which occur immediately after a single dose of an anthracycline or a course of anthracycline therapy, are uncommon under current treatment protocols. Several distinct, early cardiotoxic effects of anthracyclines have been described. First, electrophysiologic abnormalities may result in nonspecific ST and T-wave changes, decreased QRS voltage, and prolongation of the QT interval. Sinus tachycardia is the most common rhythm disturbance, but arrhythmias, including ventricular, supraventricular, and junctional tachycardias, have been reported [8-11]. Atrioventricular and bundle-branch block have also been seen [8]. These electrophysiologic changes are seldom a serious clinical problem [11]. Rare cases of subacute cardiotoxicity resulting in acute failure of the left ventricle, pericarditis, or a fatal pericarditis-myocarditis syndrome have been reported [12].
Chronic Cardiotoxicity
The incidence of congestive heart failure secondary to doxorubicin-induced cardiomyopathy depends on the cumulative dose of the drug. At total doses of less than 400 mg/m2 body surface area, the incidence of congestive heart failure is 0.14%; this incidence increases to 7% at a dose of 550 mg/m2 body surface area and to 18% at a dose of 700 mg/m2 body surface area [6] (Figure 1). The rapid increase in clinical toxicity at doses greater than 550 mg/m2 body surface area has made the 550-mg dose the popular empiric limiting dose for doxorubicin-induced cardiotoxicity. Mortality directly related to doxorubicin-induced cardiac failure is substantial; large series have reported rates of more than 20% [5, 6]. However, recent reports have suggested a better prognosis [20-24], with up to 59% clinical recovery in patients with anthracycline-induced congestive heart failure who are treated with digoxin and diuretics [14]. Complete recovery of echocardiographic shortening fraction may also occur if anthracycline therapy is discontinued at an early stage [24], but this does not exclude long-term reductions in functional reserve [23]. REVIEW
Anthracycline-Induced Cardiotoxicity
Anthracyclines are well established as highly efficacious antineoplastic agents for various hemopoietic [1] and solid tumors [2-4]. A clear dose-response relation for anthracyclines in several curative chemotherapeutic regimens has been shown; decreased doses result in inferior survival and remission rates [1, 4]. However, the cardiotoxicity of these agents [4-6], which has been recognized for more than 20 years [7], continues to limit their therapeutic potential and threaten the cardiac function of many patients with cancer.
Clinical Significance
Acute and Subacute Cardiotoxicity
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Although reports conflict, proposed risk factors for chronic anthracycline cardiotoxicity include higher rates of drug administration [25], mediastinal radiation [10, 26], advanced age [3, 6], younger age [27, 28], female sex [29], pre-existing heart disease, and hypertension [6]. Multivariate analysis of these factors by Torti and colleagues [30], based on histologic evidence of anthracycline cardiotoxicity, showed that only higher rates of anthracycline administration and previous cardiac irradiation were independent risk factors. An additional confounding factor in the identification of patients at highest risk for cardiotoxicity is the wide variation in individual sensitivity to anthracyclines [31-33]. Doses in excess of 1000 mg/m (2) body surface area can be well tolerated by some patients [31, 33]. In contrast, appreciable decreases in left ventricular ejection fraction have been documented by multigated nuclear scans at doses as low as 300 mg/m2 body surface area [26, 27]. Furthermore, endomyocardial biopsy specimens may show histopathologic changes characteristic of doxorubicin-induced cardiotoxicity Figure 2 at doses as low as 183 mg/m2 body surface area [13]—less than one third of the conventional limiting dose. Thus, a substantial proportion of patients have anthracycline-induced cardiac damage while receiving standard treatment regimens, whereas others can tolerate cumulative doses twice as large as the conventional limiting dose.
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Late-Onset Cardiotoxicity
Several recent studies have noted occult ventricular dysfunction, heart failure, and arrhythmias occurring in asymptomatic patients more than 1 year after anthracycline treatment [16-21, 34-36]. These initial findings suggest that survivors of cancer may have a previously unacknowledged increase in cardiac morbidity and mortality due to anthracycline therapy. Steinherz and associates [16], who studied 201 patients with solid tumors or leukemia, found an 18% incidence of reduced fractional shortening on resting echocardiograms in patients followed for 4 to 10 years after completion of anthracycline therapy. Even more troubling are the findings of Lipshultz and coworkers [17], who noted that cumulative doses of doxorubicin as low as 228 mg/m2 body surface area increased afterload or decreased contractility or both in 65% of patients with leukemia up to 15 years after treatment with anthracyclines. These abnormalities appear to be progressive and reflect future clinical decompensation.
Lipshultz and coworkers [17] noted both early and late congestive heart failure in 5 of 115 patients within 11 years of the completion of anthracycline therapy. A similar incidence of late-onset heart failure, occurring in 9 of 201 patients, was reported by Steinherz and associates [16]. However, most patients in the study by Steinherz and associates were followed for fewer than 10 years after completion of therapy, and new-onset symptomatic ventricular dysfunction was not seen until 12 to 14 years after treatment in the study by Lipshultz and coworkers [17]. Additionally, the incidence of severe echocardiographic abnormalities increased with the duration of follow-up (Figure 3). These findings indicate that the full extent of the problem has yet to unfold in many asymptomatic patients after remote anthracycline treatment. In addition, late-onset arrhythmias and sudden death have been reported to have occurred in patients more than 15 years after anthracycline treatment [19-21]. Incidences of nonsustained ventricular tachycardia ranging between 3% and 5% in anthracycline-treated patients at long-term follow-up have been reported [17, 19]. The natural history of these arrhythmias and whether they occur independently of ventricular dysfunction [19] are issues that remain to be clarified.
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As with the form of anthracycline cardiotoxicity that manifests earlier, the incidence of late-onset cardiac decompensation increases with larger cumulative doses [16, 17], higher rates of anthracycline administration [37], and mediastinal radiotherapy [16]. Young age [16] at the time of treatment and female sex [38] may be risk factors for late-onset anthracycline cardiotoxicity, but this is still controversial [17, 39]. However, recent evidence appears to support both characteristics as independent risk factors for late-onset ventricular dysfunction [37].
Pathogenesis
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Anthracyclines cause the selective inhibition of cardiac muscle gene expression for 
-actin, troponin, myosin light-chain 2, and the M isoform of creatine kinase in vivo [40], which may explain the myofibrillar loss (Figure 2, bottom) associated with anthracycline-induced cardiomyopathy. Hypotheses at the cellular level include free-radical-mediated myocardial injury [41-48], myocyte damage from calcium overload [49-53], disturbances in myocardial adrenergic function [54-56], release of vasoactive amines [57, 58], and cellular toxicity from metabolites of doxorubicin [59, 60]. Finally, elaboration of pro-inflammatory cytokines, which have been consistently identified in other forms of ventricular dysfunction [61-64], may be directly relevant to anthracycline-induced cardiac injury.
Although the cause of anthracycline-induced cardiotoxicity is probably multifactorial, a large body of evidence points to free-radical-mediated myocyte damage [41-44]. Increased oxygen radical activity generated through the semiquinone moiety of the doxorubicin molecule can cause lipid peroxidation and cell injury [41, 42]. Anthracycline-induced intracellular calcium overload may also lead to myocyte death [49-53]. Doxorubicin activates the calcium-release channel across the sarcoplasmic reticulum [52] and causes calcium influx into the myocyte [50, 51, 53]. Free-radical-induced cell membrane damage has also been seen with calcium influx [65, 66], suggesting that these two putative anthracycline-induced cardiotoxic pathways may be linked. Adrenergic dysfunction, including downregulation of myocardial ß-adrenergic receptors [67, 68], may be present in evolving [69, 70] as well as established anthracycline-induced ventricular dysfunction [71, 72].
Recent reports [61-64] that circulating pro-inflammatory cytokines may be intimately linked to the evolution of ventricular dysfunction and dilated cardiomyopathies may provide further insight into the process by which anthracyclines produce cardiac injury. Doxorubicin induces the release of tumor necrosis factor- from macrophages and of interleukin-2 from monocytes [73-75]. Interleukin-2 and tumor necrosis factor-, which has functional myocardial receptors [76], have documented cardiotoxicity that can result in dilated cardiomyopathy [77, 78]. Varying degrees of cytokine liberation from different tumors [79-81] during anthracycline treatment may provide another explanation for the discrepancy in the incidence of cardiotoxicity in different populations with cancer [82, 83].
Late-Onset Cardiotoxicity
Progressive ventricular dysfunction after an initial myocardial insult probably underlies late-onset decompensation. Reductions in left ventricular mass, mass index, and compliance have been reported in anthracycline-treated survivors of childhood cancer followed for more than 7 years after completion of chemotherapy [34, 84]. These patients appear to have a thin-walled left ventricle working against high systolic wall stress [34]. Such a pattern of cardiac injury is concordant with the theory that occult late-onset anthracycline cardiac dysfunction manifests clinically in patients who remain in a compensated state for many years. Acute viral infection [85] and cardiovascular stressors, such as weight lifting [20], pregnancy, and surgery, are possible triggers of late-onset anthracycline-induced cardiac dysfunction.
Monitoring
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Detection of Chronic Anthracycline-Induced Cardiomyopathy
Billingham and colleagues [86] have developed a semiquantitative histologic scoring system for endomyocardial biopsy specimens that correlates well with cumulative anthracycline dose. Biopsy grade is predictive of the rate of early progression around the time of therapy and is currently considered the most sensitive indicator of chronic anthracycline-induced cardiotoxicity [87]. Underestimation of cardiac damage with right ventricular biopsy may occur because of scattered cardiomyopathic changes [88] or the predominance of left ventricular injury [89]. Also, expertise in obtaining and interpreting biopsy specimens is not widely available, and concerns remain about the safety of repeated testing, particularly in children [90]. Thus, the use of endomyocardial biopsy for the routine monitoring of early anthracycline-induced cardiotoxicity has been limited.
Radionuclide angiocardiography is extensively used in monitoring for early anthracycline-induced cardiotoxicity on the basis of its proven value in reducing the incidence of cardiac failure from early anthracycline cardiotoxicity [91-93]. Having used data on serial left ventricular ejection fraction in patients with doxorubicin-induced cardiomyopathy, Alexander and colleagues [91] suggested that a 15% decline in left ventricular ejection fraction or a baseline left ventricular ejection fraction less than 40% identifies patients at high risk for cardiac decompensation. Similar findings by others [92, 93] have led to the proposal of broad guidelines for basing administration of anthracycline therapy on RNA findings [94]. Unfortunately, resting left ventricular ejection fraction measurements obtained through RNA findings are relatively insensitive in detecting early anthracycline cardiotoxicity. This is largely because no appreciable change in left ventricular ejection fraction occurs until a critical amount of morphologic damage has been done. After this point, functional deterioration proceeds rapidly. Exercise radionuclide studies may increase the chances of detecting subclinical early anthracycline cardiotoxicity [26, 95]. McKillop and coworkers [96] have suggested that the failure to increase ejection fraction by 5% over the resting value, as measured by stress radionuclide angiocardiography, is a marker of high risk for the development of early anthracycline-induced ventricular dysfunction. However, the specificity of exercise radionuclide angiocardiography is low without serial testing, and maximal exercise may be difficult for debilitated patients with cancer.
Two-dimensional echocardiography is the other primary noninvasive technique used to monitor anthracycline cardiotoxicity, particularly in children [97-100]. Resting left ventricular ejection fraction and fractional shortening are the most commonly used echocardiographic parameters. However, as with radionuclide measurements, cardiac compensation in the face of substantial anthracycline-induced cardiac injury often maintains normal left ventricular ejection fraction until the cardiomyopathic changes are relatively well established.
Parameters of diastolic function have also been examined for their usefulness in detecting early anthracycline-induced cardiac injury [101-108]. Chronic anthracycline cardiotoxicity can present with substantial fibrous thickening of the endocardium [89], suggesting that diastolic dysfunction is probably an impairment co-existing with the disease. Marchandise and coworkers [101], in an echocardiographic study, found a prolongation of the isovolumic relaxation period of 32% (from 65 ms to 86 ms) and a reduction in early peak flow velocity of 18% (from 60 ms to 49 ms) in anthracycline-treated adults before detectable decreases in left ventricular shortening fraction, which remained at about 40% [101]. In addition, Stoddard and colleagues [103] have reported an increase in the mean isovolumic relaxation time from 66 to 84 ms after cumulative doxorubicin doses as low as 100 mg/m2 body surface area in a prospective study of 26 anthracycline-treated adults. These authors have suggested that an increase in the isovolumic relaxation time of more than 37% reliably predicts anthracycline-induced systolic dysfunction (defined as a decrease in ejection fraction of less than equals 10% to less than 55%). Other echocardiographic diastolic parameters, such as rapid and slow filling velocities [103], have also been reported to precede anthracycline-induced systolic dysfunction in adults. Reductions in peak filling rate, a diastolic parameter measured by multigated angiocardiography in adults, occur before anthracycline-induced decrements in left ventricular ejection fraction [104]. However, a recent report on anthracycline-treated adults [107] suggests that reductions in peak filling rate and ejection fraction measured by radionuclide studies appear simultaneously. The utility of diastolic filling abnormalities to unmask early anthracycline cardiotoxicity in children also needs to be confirmed [105-108]. Fractional shortening has been reported to be more sensitive than diastolic parameters in children with early anthracycline-induced cardiomyopathy [106]. In contrast, a recent smaller prospective study has shown the value of diastolic indices in detecting early anthracycline-induced cardiomyopathy in asymptomatic children [108]. Table 1 summarizes studies examining diastolic and systolic abnormalities in early anthracycline-induced cardiotoxicity. Despite inherent limitations in sensitivity, resting left ventricular ejection fraction based on radionuclide angiocardiography or echocardiography remains the most widely used monitoring method for early anthracycline-induced cardiotoxicity. The limited sizes of these studies (the largest of which involved 60 patients) underscore the need for larger prospective studies to establish the value of diastolic abnormalities in the detection of early anthracycline-induced cardiotoxicity.
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Detection of Late-Onset Anthracycline-Induced Cardiotoxicity
Recognition of late-onset cardiac dysfunction and failure has highlighted the need for monitoring methods that will help detect and predict long-term cardiac impairment in asymptomatic patients. Currently, there are few universally accepted guidelines on which tests of ventricular function should directly influence long-term monitoring for late-onset cardiotoxicity in asymptomatic adults, although the issue has been extensively debated in children [97-99]. Lipshultz and coworkers [17] have reported that fractional shortening as assessed by echocardiography has a sensitivity of 64% and a specificity of 81% for either abnormal contractility or abnormal afterload at long-term follow-up [17]. Congruent with these findings are the results of Steinherz and colleagues [16]. In a study of 201 children treated with anthracycline, they found that only 29% of patients with mildly abnormal or worse fractional shortening (
28%) on an "end-therapy" echocardiogram had normal fractional shortening (
29%) at late follow-up. Thus, abnormal fractional shortening after therapy may help predict long-term cardiac dysfunction. In contrast, 87% of patients with normal fractional shortening during the first year after therapy have maintained normal fractional shortening at late follow-up [16]. However, most late-onset clinical decompensations occur after more than 10 years of follow-up, and data from beyond that time point are limited. Echocardiographically determined left ventricular end-systolic wall stress (a more load-independent measure of systolic function than fractional shortening) has also been used to assess late-onset anthracycline-induced cardiotoxicity. Lipshultz and coworkers [17] have reported that left ventricular end-systolic wall stress is substantially increased to a mean of 64 g/cm2 (normal mean, 47.5 g/cm2) in anthracycline-induced late-onset ventricular dysfunction, although correlation with symptoms was poor.
Resting left ventricular ejection fraction and fractional shortening are often absent despite substantial decreases in functional capacity associated with late-onset cardiotoxicity [109-111]. Dobutamine [109], exercise echocardiography [110], and exercise radionuclide angiography [111] have all been shown to unmask late-onset cardiac dysfunction in small series of patients with normal resting systolic function. Using dobutamine echocardiography in a group of patients treated with anthracycline, Klewer and coworkers [109] found significant reductions in shortening fraction and end-systolic wall stress that were only detectable during inotropic stimulation a mean of 6.1 years after therapy. Yeung and colleagues [18] tested 29 children, 19 of whom had received anthracyclines up to 6 years earlier with exercise echocardiography. The children treated with anthracycline had an average increase in fractional shortening of 3% compared with an average increase of 23% in the control group, although fractional shortening at rest was normal (mean, 38%) in all participants [18].
Diastolic dysfunction can also be seen with late-onset anthracycline-induced systolic impairment, particularly in patients who have received high doses of anthracyclines with radiotherapy [112]. Concordant with these findings, preliminary data from anthracycline-treated survivors of leukemia suggest that features of restrictive cardiomyopathy may appear on long-term follow-up [84]. Table 2 summarizes studies evaluating ventricular function during long-term (> 1 year) follow-up after anthracycline treatment.
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From the standpoint of the clinician, it is unclear how much information in addition to that on resting systolic parameters is derived from the use of diastolic and stress systolic indices during screening for either early or late anthracycline-induced cardiotoxicity. Larger prospective studies are needed to provide more conclusive data on the correlation between these noninvasive parameters and 1) the overall frequency of early- and late-onset anthracycline-induced cardiotoxicity, 2) clinically important functional impairment, and 3) mortality from anthracycline-induced heart failure. Also, the value of early abnormalities in determining the need for long-term monitoring of late-onset cardiotoxicity needs to be clarified. The advantages and limitations of noninvasive assessment of ventricular function have been well reviewed [113, 114].
Although the full clinical importance of systolic and diastolic dysfunction in anthracycline-induced cardiomyopathy is unclear, it may be useful to consider the clinical relevance of diastolic and systolic abnormalities in patients with idiopathic dilated cardiomyopathy [115-117]. In addition to decreased left ventricular ejection fraction [115], such diastolic abnormalities as shortened deceleration time [115, 116] and increased peak early velocity [116] have been reported as further markers of poor prognosis. Diastolic dysfunction strongly correlates with congestive symptoms in patients with dilated cardiomyopathy [115, 117]. Confirmation of such findings in patients with anthracycline-induced cardiomyopathy would be valuable in the assessment of prognosis and the rationalization of monitoring for anthracycline-induced cardiotoxicity.
Prevention
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First, the method of drug delivery [25, 118, 119] may influence cardiotoxicity. In adults, less clinical cardiotoxicity has been noted with prolonged infusions of doxorubicin over 48 or 96 hours than with shorter infusion times of 15 to 20 minutes [25]. However, concern about whether antineoplastic activity is preserved with this regimen remains [118], and the value of this approach has not been proven in children. An alternative way to deliver drug with potentially less cardiotoxicity is to use liposomal anthracyclines, which are now in Phase II clinical trials [119]. Second, the use of such anthracycline structural analogues as mitoxantrone and idarubicin is of undetermined benefit in the balance between cardiotoxicity and antineoplastic effect [31].
Third, cardioprotectants are used to attenuate the effects of anthracyclines on the heart. Randomized, placebo-controlled studies in patients with breast cancer have shown that cardioprotection occurs with dexrazoxane (ICRF-187), an iron-chelating agent that appears to reduce free-radical generation by anthracyclines [120-123]. This agent has also shown the promise of cardioprotection in children [124]. Dexrazoxane is currently clinically approved only for use in women with metastatic breast cancer after a cumulative doxorubicin dose of 300 mg/m2 body surface area. However, substantial myocardial damage can be expected at much lower doses. In addition, concerns that dexrazoxane interferes with the antitumor efficacy of anthracyclines have been raised [125]; lower response rates and faster tumor progression times have been seen in patients with early breast cancer [122].
Recent animal studies indicate that probucol, a lipid-lowering agent similar in structure to vitamin E, provides cardioprotection against doxorubicin-induced cardiomyopathy [46, 48]. Siveski-Iliskovic and associates [46] have reported that probucol enhances antioxidants in the rat myocardium by increasing myocardial glutathione peroxidase and superoxide dismutase activities. A reduction in anthracycline-induced lipid peroxidation occurred concomitantly with this improvement in myocardial antioxidant status [46]. Furthermore, probucol does not interfere with the antitumor effects of doxorubicin in this animal model [47]. Studies in humans are needed to determine whether these findings can be extrapolated to clinical practice.
The prevention of intracellular calcium overload caused by anthracyclines has also been targeted as a cardioprotective maneuver. Animal models have suggested that calcium antagonists both enhance and reduce anthracycline cardiotoxicity with calcium antagonists [126-129]; pilot data indicate that the calcium antagonist prenylamine may confer some cardioprotection in humans [130]. ß-adrenergic blocking agents have been shown to prevent anthracycline-induced intracellular calcium overload [131] and reduce anthracycline-induced cardiotoxicity, possibly by blunting the cardiotoxic effect of catecholamines [126]. Lipophilic ß-blockers, such as propranolol, can also prevent free-radical-mediated lipid peroxidation [132-134]. The safe and efficacious use of metoprolol in established anthracycline-induced cardiomyopathy [135], idiopathic dilated cardiomyopathy [136], and ischemic heart failure [137] have all been reported. However, the cardioprotective effects of ß-blockers against anthracycline-induced cardiotoxicity remain untested in prospective studies.
Conclusions
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This review is limited by the relatively small numbers of patients and the retrospective data included in some studies; these factors may confound the accuracy of clinical predictions [145, 146]. Concurrent occult disease, including subclinical coronary artery disease, silent infarction, and hypertensive heart disease, may have affected the interpretation of the overall effect of anthracycline-induced cardiotoxicity. Consideration of studies involving anthracycline-treated children and adults together may also make global inferences from these studies more difficult, particularly with regard to ventricular function tests and the effects of cardiovascular risk factors. In addition, the heterogeneity of the types of cancer among the various study populations may also influence the observed incidence of heart failure because of different treatment regimens, adjunctive radiotherapies, and hydration regimens. Finally, many of the studies that address the efficacy of monitoring are limited by a lack of prospective clinical data on prognosis and functional class.
Long-term follow-up shows that overt heart failure occurs in 4.5% to 7% of patients treated with anthracycline and that the incidence of cardiac function abnormalities increases with time. However, the lack of information about the cardiac status of patients more than 15 years after the completion of anthracycline therapy is troubling. As we await more extended cardiac follow-up, the grave prognosis for patients with anthracycline-induced cardiomyopathy is ominous [6]. Despite the qualified success of dexrazoxane, the need for widely applicable cardioprotection against anthracyclines is increasingly pressing.
Acknowledgments: The authors thank Kathleen D. Saneto for assistance in manuscript preparation and Dr. Jocelyn F. Caple for providing (Figure 2).
Author and Article Information
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References
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1. Hitchcock-Bryan S, Gelber RD, Cassady JR, Sallan SE. The impact of induction anthracycline on long-term failure-free survival in childhood acute lymphoblastic leukemia. Med Pediatr Oncol. 1986; 14:211-5.
2. Bonadonna G, Zambetti M, Valagussa P. Sequential or alternating doxorubicin and CMF regimens in breast cancer with more than three positive nodes. Ten-year results. JAMA. 1996; 273:542-7.
3. Fisher B, Redmond C, Wickerham DL, Bowman D, Schipper H, Wolmark N, et al. Doxorubicin-containing regimens for the treatment of stage II breast cancer: The National Surgical Adjuvant Breast and Bowel Project experience. J Clin Oncol. 1989; 7:572-82.
4. Ettinghausen SE, Bonow RO, Palmeri ST, Seipp CA, Steinberg SM, White DE, et al. Prospective study of cardiomyopathy induced by adjuvant doxorubicin therapy in patients with soft-tissue sarcomas. Arch Surg. 1986; 121:1445-51.
5. Praga C, Beretta G, Vigo PL, Lenaz GR, Pollini C, Bonadonna G, et al. Adriamycin cardiotoxicity: a survey of 1273 patients. Cancer Treat Rep. 1979; 63:827-34.
6. Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979; 91:710-7.
7. Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer. 1973; 32:302-14.
8. Steinberg JS, Cohen AJ, Wasserman AG, Cohen P, Ross AM. Acute arrhythmogenicity of doxorubicin administration. Cancer. 1987; 60:1213-8.
9. Lenaz L, Page JA. Cardiotoxicity of adriamycin and related anthracyclines. Cancer Treat Rev. 1976; 3:111-20.
10. Ferrans VJ. Overview of cardiac pathology in relation to anthracycline cardiotoxicity. Cancer Treat Rep. 1978; 62:955-61.
11. Von Hoff DD, Rozencweig M, Layard M, Slavik M, Muggia FM. Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases. Am J Med. 1977; 62:200-8.[Medline]
12. Bristow MR, Billingham ME, Mason JW, Daniels JR. Clinical spectrum of anthracycline antibiotic cardiotoxicity. Cancer Treat Rep. 1978; 62:873-9.
13. Friedman MA, Bozdech MJ, Billingham ME, Rider AK. Doxorubicin cardiotoxicity. Serial endomyocardial biopsies and systolic time intervals. JAMA. 1978; 240:1603-6.
14. Haq MM, Legha SS, Choksi J, Hortobagyi GN, Benjamin RS, Ewer M, et al. Doxorubicin-induced congestive heart failure in adults. Cancer. 1985; 56:1361-5.
15. Schwartz RG, McKenzie WB, Alexander J, Sager P, D'Souza A, Manatunga A, et al. Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography. Am J Med. 1987; 82:1109-18.
16. Steinherz LJ, Steinherz PG, Tan CT, Heller G, Murphy ML. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA. 1991; 266:1672-7.
17. Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med. 1991; 324:808-15.
18. Yeung ST, Yoong C, Spink J, Galbraith A, Smith PJ. Functional myocardial impairment in children treated with anthracyclines for cancer. Lancet. 1991; 337:816-8.
19. Larsen RL, Jakacki RI, Vetter VL, Meadows AT, Silber JH, Barber G. Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. Am J Cardiol. 1992; 70:73-7.
20. Steinherz LJ, Steinherz PG, Tan C. Cardiac failure and dysrhythmias 6-19 years after anthracycline therapy: a series of 15 patients. Med Pediatr Oncol. 1995; 24:352-61.
21. Steinherz L, Steinherz P. Delayed cardiac toxicity from anthracycline therapy. Pediatrician. 1991; 18:49-52.
22. Goorin AM, Borow KM, Goldman A, Williams RG, Henderson IC, Sallan SE, et al. Congestive heart failure due to adriamycin cardiotoxicity: its natural history in children. Cancer. 1981; 47:2810-6.
23. Moreb JS, Oblon DJ. Outcome of clinical congestive heart failure induced by anthracycline chemotherapy. Cancer. 1992; 70:2637-41.
24. Lewis AB, Crouse VL, Evans W, Takahashi M, Siegel SE. Recovery of left ventricular function following discontinuation of anthracycline chemotherapy in children. Pediatrics. 1981; 68:67-72.
25. Legha SS, Benjamin RS, Mackay B, Ewer M, Wallace S, Valdivieso M, et al. Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med. 1982; 96:133-9.
26. Bristow MR, Mason JW, Billingham ME, Daniels JR. Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. Ann Intern Med. 1978; 88:168-75.
27. Cortes EP, Lutman G, Wanka J, Wang JJ, Pickren J, Wallace J, et al. Adriamycin (NSC-123127) cardiotoxicity: a clinicopathologic correlation. Cancer Chemother Rep. 1975; 6:215-25.
28. Pratt CB, Ransom JL, Evans WE. Age-related adriamycin cardiotoxicity in children. Cancer Treat Rep. 1978; 62:1381-5.
29. Cuthbertson DD, Epstein ST, Lipshultz SE, Goorin AM, Epstein ML, Krischer JP. Anthracycline cardiotoxicity in children with cancer [Abstract]. Circulation. 1994; 90(Suppl):1-50.
30. Torti FM, Bristow MR, Howes AE, Aston D, Stockdale FE, Carter SK, et al. Reduced cardiotoxicity of doxorubicin delivered on a weekly schedule. Assessment by endomyocardial biopsy. Ann Intern Med. 1983; 99:745-9.
31. Henderson IC, Allegra JC, Woodcock T, Wolff S, Bryan S, Cartwright K, et al. Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer. J Clin Oncol. 1989; 7:560-71.
32. Speyer JL, Green MD, Dubin N, Blum RH, Wernz JC, Roses D, et al. Prospective evaluation of cardiotoxicity during a six-hour doxorubicin infusion regimen in women with adenocarcinoma of the breast. Am J Med. 1985; 78:555-63.
33. Bristow MR, Thompson PD, Martin RP, Mason JW, Billingham ME, Harrison DC. Early anthracycline cardiotoxicity. Am J Med. 1978; 65:823-32.
34. Leandro J, Dyck J, Poppe D, Shore R, Airhart C, Greenberg M, et al. Cardiac dysfunction late after cardiotoxic therapy for childhood cancer. Am J Cardiol. 1994; 74:1152-6.
35. Jakacki R, Silber J, Larsen R, Barber G, Goldwein J, Meadows A. Cardiac dysfunction following "low risk" cardiotoxic treatment for childhood malignancy [Abstract]. Pediatr Res. 1991; 29:143A.
36. LaMonte CS, Yeh SD, Straus DJ. Long-term follow-up of cardiac function in patients with Hodgkin's disease treated with mediastinal irradiation and combination chemotherapy including doxorubicin. Cancer Treat Rep. 1986; 70:439-44.
37. Lipshultz SE, Lipsitz SR, Mone SM, Goorin AM, Sallan SE, Sanders SP, et al. Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med. 1995; 332:1738-43.
38. Silber JH, Jakacki RI, Larsen RL, Goldwein JW, Barber G. Increased risk of cardiac dysfunction after anthracyclines in girls. Med Pediatr Oncol. 1993; 21:477-9.
39. Bu'Lock FA, Martin RP, Mott MG. Increased risk of cardiac dysfunction after anthracyclines in girls [Letter]. Med Pediatr Oncol. 1995; 24:143-4.
40. Ito H, Miller SC, Billingham ME, Akimoto H, Torti SV, Wade R, et al. Doxorubicin selectively inhibits muscle gene expression in cardiac muscle cells in vivo and in vitro. Proc Natl Acad Sci U S A. 1990; 87:4275-9.
41. Doroshow JH. Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res. 1983; 43:460-72.
42. Rajagopalan S, Politi PM, Sinha BK, Myers CE. Adriamycin-induced free radical formation in the perfused rat heart: implications for cardiotoxicity. Cancer Res. 1988; 48:4766-9.
43. Jackson JA, Reeves JP, Muntz KH, Kruk D, Prough RA, Willerson JT, et al. Evaluation of free radical effects and catecholamine alterations in adriamycin cardiotoxicity. Am J Pathol. 1984; 117:140-53.
44. Myers CE, McGuire WP, Liss RH, Ifrim I, Grotzinger K, Young RC. Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response. Science. 1977; 197:165-7.
45. Doroshow JH, Locker GY, Myers CE. Enzymatic defenses of the mouse heart against reactive oxygen metabolites: alterations produced by doxorubicin. J Clin Invest. 1980; 65:128-35.
46. Siveski-Iliskovic N, Kaul N, Singal PK. Probucol promotes endogenous antioxidants and provides protection against adriamycin-induced cardiomyopathy in rats. Circulation. 1994; 89:2829-35.
47. Siveski-Iliskovic N, Hill M, Chow DA, Singal PK. Probucol protects against adriamycin cardiomyopathy without interfering with its antitumor effect. Circulation. 1995; 91:10-5.
48. Singal PK, Siveski-Iliskovic N, Hill M, Thomas TP, Li T. Combination therapy with probucol prevents adriamycin-induced cardiomyopathy. J Mol Cell Cardiol. 1995; 27:1055-63.
49. Singal PK, Pierce GN. Adriamycin stimulates low-affinity Ca2+ binding and lipid peroxidation but depresses myocardial function. Am J Physiol. 1986; 250(3 Pt 2):H419-25.
50. Olson HM, Young DM, Prieur DJ, LeRoy AF, Reagan RL. Electrolyte and morphologic alterations of myocardium in adriamycin-treated rabbits. Am J Pathol. 1974; 77:439-54.
51. Kusuoka H, Futaki S, Koretsune Y, Kitabatake A, Suga H, Kamada T, et al. Alterations of intracellular calcium homeostasis and myocardial energetics in acute adriamycin-induced heart failure. J Cardiovasc Pharmacol. 1991; 18:437-44.
52. Holmberg SR, Williams AJ. Patterns of interaction between anthraquinone drugs and the calcium-release channel from cardiac sarcoplasmic reticulum. Circ Res. 1990; 67:272-83.
53. Wang YX, Korth M. Effects of doxorubicin on excitation-contraction coupling in guinea pig ventricular myocardium. Circ Res. 1995; 76:645-53.
54. Wakasugi S, Wada A, Hasegawa Y, Nakano S, Shibata N. Detection of abnormal cardiac adrenergic neuron activity in adriamycin-induced cardiomyopathy with iodine-125-metaiodobenzylguanidine. J Nucl Med. 1992; 33:208-14.
55. Valdes Olmos RA, ten Bokkel Huinink WW, Greve JC, Hoefnagel CA. 1-123 MIBG and serial radionuclide angiocardiography in doxorubicin-related cardiotoxicity. Clin Nucl Med. 1992; 17:163-7.[Medline]
56. Valdes Olmos RA, ten Bokkel Huinink WW, ten Hoeve RF, van Tinteren H, Bruning PF, van Vlies B, et al. Assessment of anthracycline-related myocardial adrenergic derangement by123 I)metaiodobenzylguanidine scintigraphy. Eur J Cancer. 1995; 31A:26-31.
57. Bristow MR, Minobe WA, Billingham ME, Marmor JB, Johnson GA, Ishimoto BM, et al. Anthracycline-associated cardiac and renal damage in rabbits. Evidence for mediation by vasoactive substances. Lab Invest. 1981; 45:157-68.
58. Bristow MR, Kantrowitz NE, Harrison WD, Minobe WA, Sageman WS, Billingham ME, et al. Mediation of subacute anthracycline cardiotoxicity in rabbits by cardiac histamine release. J Cardiovasc Pharmacol. 1983; 5:913-9.
59. Minotti G, Cavaliere AF, Mordente A, Rossi M, Schiavello R, Zamparelli R, et al. Secondary alcohol metabolites mediate iron delocalization in cytosolic fractions of myocardial biopsies exposed to anticancer anthracyclines. Novel linkage between anthracycline metabolism and iron-induced cardiotoxicity. J Clin Invest. 1995; 95:1595-605.
60. Boucek RJ Jr, Olson RD, Brenner DE, Ogunbunmi EM, Inui M, Fleischer S. The major metabolite of doxorubicin is a potent inhibitor of membrane-associated ion pumps. A correlative study of cardiac muscle with isolated membrane fractions. J Biol Chem. 1987; 262:15851-6.
61. Matsumori A, Yamada T, Suzuki H, Matoba Y, Sasayama S. Increased circulating cytokines in patients with myocarditis and cardiomyopathy. Br Heart J. 1994; 72:561-6.
62. Ferrari R, Bachetti T, Confortini R, Opasich C, Febo O, Corti A, et al. Tumor necrosis factor soluble receptors in patients with various degrees of congestive hear failure. Circulation. 1995; 92:1479-86.
63. Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann DL. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the studies of left ventricular dysfunction (SOLVD). J Am Coll Cardiol. 1996: [in press].
64. Mann DL, Young JB. Basic mechanisms in congestive heart failure. Recognizing the role of proinflammatory cytokines. Chest. 1994; 105:897-904.
65. Holmberg SR, Cumming DV, Kusama Y, Hearse DJ, Poole-Wilson PA, Shattock MJ, et al. Reactive oxygen species modify the structure and function of the cardiac sarcoplasmic reticulum calcium-release channel. Cardioscience. 1991; 2:19-25.
66. Burton KP, Morris AC, Massey KD, Buja LM, Hagler HK. Free radicals alter ionic calcium levels and membrane phospholipids in cultured rat ventricular myocytes. J Mol Cell Cardiol. 1990; 22:1035-47.
67. Fujita N, Hiroe M, Ohta Y, Horie T, Hosoda S. Chronic effects of metoprolol on myocardial ß-adrenergic receptors in doxorubicin-induced cardiac damage in rats. J Cardiovasc Pharmacol. 1991; 17:656-61.
68. Robison TW, Giri SN. Effects of chronic administration of doxorubicin on myocardial ß-adrenergic receptors. Life Sci. 1986; 39:731-6.
69. Tong J, Ganguly PK, Singal PK. Myocardial adrenergic changes at two stages of heart failure due to adriamycin treatment in rats. Am J Physiol. 1991; 260(3 Pt 2):H909-16.
70. Yoshikawa T, Handa S, Suzuki M, Nagami K. Abnormalities in sympathoneuronal regulation are localized to failing myocardium in rabbit heart. J Am Coll Cardiol. 1994; 24:210-5.
71. Floras JS. Clinical aspects of sympathetic activation and parasympathetic withdrawal in heart failure. J Am Coll Cardiol. 1993; 22(4 Suppl A):72A-84A.
72. Benedict CR, Weiner DH, Johnstone DE, Bourassa MG, Ghali JK, Nicklas J, et al. Comparative neurohormonal responses in patients with preserved and impaired left ventricular ejection fraction: results of the Studies of Left Ventricular Dysfunction (SOLVD) Registry. J Am Coll Cardiol. 1993; 22(4 Suppl A):146A-53A.
73. Ehrke MJ, Maccubbin D, Ryoyama K, Cohen SA, Mihich E. Correlation between adriamycin-induced augmentation of interleukin 2 production and of cell-mediated cytotoxicity in mice. Cancer Res. 1986; 46:54-60.
74. Shi F, MacEwen EG, Kurzman ID. In vitro and in vivo effect of doxorubicin combined with liposome-encapsulated muramyl tripeptide on canine monocyte activation. Cancer Res. 1993; 53:3986-91.
75. Abdul Hamied TA, Parker D, Turk JL. Effects of adriamycin, 4-hydroperoxycyclophosphamide and ASTA Z 7557 (INN mafosfamide) on the release of IL-2 and IL-1 in vitro. Int J Immunopharmacol. 1987; 9:355-61.[Medline]
76. Torre-Amione G, Kapadia S, Lee J, Bies RD, Lebovitz R, Mann DL. Expression and functional significance of tumor necrosis factor receptors in human myocardium. Circulation. 1995:92:1487-93.
77. Hegewisch S, Weh HJ, Hossfeld DK. TNF-induced cardiomyopathy [Letter]. Lancet. 1990; 335:294-5.
78. Beck AC, Ward JH, Hammond EH, Wray RB, Samlowski WE. Cardiomyopathy associated with high-dose interleukin-2 therapy. West J Med. 1991; 155:293-6.
79. Raziuddin S, Sheikha A, Abu-Eshy S, al-Janadi M. Circulating levels of cytokines and soluble cytokine receptors in various T-cell malignancies. Cancer. 1994; 73:2426-31.
80. Elbaz O, Mahmoud LA. Tumor necrosis factor and human acute leukemia. Leuk Lymphoma. 1994; 12:191-5.
81. Anastasopoulos E, Reclos GJ, Baxevanis CN, Gritzapis AD, Tsilivakos V, Panagiotopoulos N, et al. Monocyte disorders associated with T cell defects in patients with solid tumors. Anticancer Res. 1992; 12:489-94.
82. Sorensen K, Levitt G, Sebag-Montefiore D, Bull C, Sullivan I. Cardiac function in Wilms' tumor survivors. J Clin Oncol. 1995; 13:1546-56.
83. Hancock SL, Tucker MA, Hoppe RT. Factors affecting late mortality from heart disease after treatment of Hodgkin's disease. JAMA. 1993; 270:1949-55.
84. Lipshultz SE, Lipsitz SR, Mone SM, Sallan SE, Colan SD. Left ventricular structure and function eleven years after doxorubicin treatment for childhood leukemia: is this a restrictive cardiomyopathic process? [Abstract] J Am Coll Cardiol. 1995; 25:54A.
85. Ali MK, Ewer MS, Gibbs HR, Swafford J, Graff KL. Late doxorubicin-associated cardiotoxicity in children. The possible role of intercurrent viral infection. Cancer. 1994; 74:182-8.
86. Billingham ME, Bristow MR. Evaluation of anthracycline cardiotoxicity: predictive ability and functional correlation of endomyocardial biopsy. Cancer Treatment Symposia. 1984; 3:71-6.
87. Mason JW, Bristow MR, Billingham ME, Daniels JR. Invasive and noninvasive methods of assessing adriamycin cardiotoxic effects in man: superiority of histopathologic assessment using endomyocardial biopsy. Cancer Treat Rep. 1978; 62:857-64.
88. Isner JM, Ferrans VJ, Cohen SR, Witkind BG, Virmani R, Gottdiener JS, et al. Clinical and morphologic cardiac findings after anthracycline chemotherapy. Analysis of 64 patients studied at necropsy. Am J Cardiol. 1983; 51:1167-74.
89. Mortensen SA, Olsen HS, Baandrup U. Chronic anthracycline cardiotoxicity: haemodynamic and histopathological manifestations suggesting a restrictive endomyocardial disease. Br Heart J. 1986; 55:274-82.
90. Pegelow CH, Popper RW, de Wit SA, King OY, Wilbur JR. Endomyocardial biopsy to monitor anthracycline therapy in children. J Clin Oncol. 1984; 2:443-6.
91. Alexander J, Dainiak N, Berger HJ, Goldman L, Johnstone D, Reduto L, et al. Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide angiocardiography. N Engl J Med. 1979; 300:278-83.
92. Piver MS, Marchetti DL, Parthasarathy KL, Bakshi S, Reese P. Doxorubicin hydrochloride (Adriamycin) cardiotoxicity evaluated by sequential radionuclide angiocardiography. Cancer. 1985; 56:76-80.
93. Ritchie JL, Singer JW, Thorning D, Sorensen SG, Hamilton GW. Anthracycline cardiotoxicity: clinical and pathologic outcomes assessed by radionuclide ejection fraction. Cancer. 1980; 46:1109-16.
94. Zaret BL, Schwartz PE, Berger HJ, Schwartz RG. Evaluation of doxorubicin cardiotoxicity with radionuclide angiocardiography at rest. Cancer Treatment Symposia. 1984; 3:61-6.
95. Bristow MR, Mason JW, Billingham ME, Daniels JR. Dose-effect and structure-function relationships in doxorubicin cardiomyopathy. Am Heart J. 1981; 102:709-18.
96. McKillop JH, Bristow MR, Goris ML, Billingham ME, Bockemuehl K. Sensitivity and specificity of radionuclide ejection fractions in doxorubicin cardiotoxicity. Am Heart J. 1983; 106:1048-56.
97. Steinherz LJ, Graham T, Hurwitz R, Sondheimer HM, Schwartz RG, Shaffer EM, et al. Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Childrens Cancer Study Group. Pediatrics. 1992; 89(5 Pt 1):942-9.
98. Lipshultz SE, Sanders SP, Goorin AM, Krischer JP, Sallan SE, Colan SD, et al. Monitoring for anthracycline cardiotoxicity. Pediatrics. 1994; 93:433-37.
99. Steinherz LJ, Graham T, Hurwitz R, Sondheimer HM, Schwartz RG, Sandor G, et al. Guidelines for monitoring of anthracycline cardiomyopathy: a rebuttal [Letter]. Pediatrics. 1994; 94:782-4.
100. Borow KM, Henderson IC, Neuman A, Colan S, Grady S, Papish S, et al. Assessment of left ventricular contractility in patients receiving doxorubicin. Ann Intern Med. 1983; 99:750-6.
101. Marchandise B, Schroeder E, Bosly A, Doyen C, Weynants P, Kremer R, et al. Early detection of doxorubicin cardiotoxicity: interest of Doppler echocardiographic analysis of left ventricular filling dynamics. Am Heart J. 1989; 118:92-8.
102. Lee BH, Goodenday LS, Muswick GJ, Yasnoff WA, Leighton RF, Skeel RT. Alternations in left ventricular diastolic function with doxorubicin therapy. J Am Coll Cardiol. 1987; 9:184-8.
103. Stoddard MF, Seeger J, Liddell NE, Hadley TJ, Sullivan DM, Kupersmith J. Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans. J Am Coll Cardiol. 1992; 20:62-9.
104. Ganz WI, Sridhar KS, Forness TJ. Detection of early anthracycline cardiotoxicity by monitoring the peak filling rate. Am J Clin Oncol. 1993; 16:109-12.
105. Hausdorf G, Morf G, Beron G, Erttmann R, Winkler K, Landbeck G, et al. Long term doxorubicin cardiotoxicity in childhood: non-invasive evaluation of the contractile state and diastolic filling. Br Heart J. 1988; 60:309-15.
106. Ewer MS, Ali MK, Gibbs HR, Swafford J, Graff KL, Cangir A, et al. Cardiac diastolic function in pediatric patients receiving doxorubicin. Acta Oncol. 1994; 33:645-9.
107. Cottin Y, Touzery C, Coudert B, Gilles A, Walker P, Massing JL, et al. Impairment of diastolic function during short-term anthracycline chemotherapy. Br Heart J. 1995; 73:61-4.
108. Schmitt K, Tulzer G, Merl M, Alchhorn G, Grillenberger A, Wiesinger G, et al. Early detection of doxorubicin and daunorubicin cardiotoxicity by echocardiography: diastolic versus systolic parameters. Eur J Pediatr. 1995; 154:201-4.
109. Klewer SE, Goldberg SJ, Donnerstein RL, Berg RA, Hutter JJ Jr. Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer. J Am Coll Cardiol. 1992; 19:394-401.
110. Weesner KM, Bledsoe M, Chauvenet A, Wofford M. Exercise echocardiography in the detection of anthracycline cardiotoxicity. Cancer. 1991; 68:435-8.
111. Gottdiener JS, Mathisen DJ, Borer JS, Bonow RO, Myers CE, Barr LH, et al. Doxorubicin cardiotoxicity: assessment of late left ventricular dysfunction by radionuclide cineangiography. Ann Intern Med. 1981; 94(4 Pt 1):430-5.
112. Bu'Lock FA, Mott MG, Oakhill A, Martin RP. Left ventricular diastolic function after anthracycline chemotherapy in childhood: relation with systolic function, symptoms, and pathophysiology. Br Heart J. 1995; 73:340-50.
113. Dell'ltalia LJ, Freeman GL, Gaasch WH. Cardiac function and functional capacity: implications for the failing heart. Curr Probl Cardiol. 1993; 18:705-58.
114. Pai RG, Shah PM. Echocardiographic and other noninvasive measurements of cardiac hemodynamics ventricular function. Curr Probl Cardiol. 1995; 20:681-770.
115. Rihal CR, Nishimura RA, Hatle LK, Bailey KR, Tajik AJ. Systolic and diastolic dysfunction in patients with clinical diagnosis of dilated cardiomyopathy. Relation to symptoms and prognosis. Circulation. 1994; 90:2772-9.
116. Werner GS, Schaefer C, Dirks R, Figulla HC, Kreuzer H. Prognostic value of Doppler echocardiographic assessment of left ventricular filling in idiopathic dilated cardiomyopathy. Am J Cardiol. 1994; 73:792-8.
117. Belardinelli R, Georgiou D, Cianci G, Berman N, Gintzon L, Purcaro A. Exercise training improves left ventricular diastolic filling in patients with dilated cardiomyopathy. Clinical and prognostic implications. Circulation. 1995; 91:2775-84.
118. Bielack SS, Erttmann R, Winkler K, Landbeck G. Doxorubicin: effect of different schedules on toxicity and anti-tumor efficacy. Eur J Cancer Clin Oncol. 1989; 25:873-82.
119. Treat J, Greenspan A, Forst D, Sanchez JA, Ferrans VJ, Potkul LA, et al. Antitumor activity of liposome-encapsulated doxorubicin in advanced breast cancer: phase II study. J Natl Cancer Inst. 1990; 82:1706-10.
120. Speyer JL, Green MD, Zeleniuch-Jacquotte A, Wernz JC, Rey M, Sanger J, et al. ICRF-187 permits longer treatment with doxorubicin in women with breast cancer. J Clin Oncol. 1992; 10:117-27.
121. Speyer JL, Green MD, Kramer E, Rey M, Sanger J, Ward C, et al. Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer. N Engl J Med. 1988; 319:745-52.
122. Seifert CF, Nesser ME, Thompson DF. Dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity. Ann Pharmacother. 1994; 28:1063-72.
123. Kolaric K, Bradamante V, Cervek J, Cieslinska A, Cisarz-Filipcak E, Denisov LE, et al. A phase-II trial of cardioprotection with Cardioxane (ICRF-187) in patients with advanced breast cancer receiving 5-fluorouracil, doxorubicin and cyclophosphamide. Oncology. 1995; 52:251-5.
124. Bu'Lock FA, Gabriel HM, Oakhill A, Mott MG, Martin RP. Cardioprotection by ICRF187 against high dose anthracycline toxicity in children with malignant disease. Br Heart J. 1993; 70:185-8.
125. Sehested M, Jensen PB, Sorensen BS, Holm B, Friche E, Demant EJ. Antagonistic effect of the cardioprotector (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF-187) on DNA breaks and cytotoxicity induced by the topoisomerase II directed drugs daunoribicin and etoposide (VP-16). Biochem Pharmacol. 1993; 46:389-93.
126. Bristow MR, Sageman WS, Scott RH, Billingham ME, Bowden RE, Kernoff RS, et al. Acute and chronic cardiovascular effects of doxorubicin in the dog: the cardiovascular pharmacology of drug-induced histamine release. J Cardiovasc Pharmacol. 1980; 2:487-515.
127. Wikman-Coffelt J, Rapcsak M, Sievers R, Rouleau JL, Parmley WW. Verapamil, propranolol, and hydralazine protect against the acute cardiac depression induced by adriamycin. Cardiovasc Res. 1983; 17:43-9.
128. Santostasi G, Kutty RK, Krishna G. Increased toxicity of anthracycline antibiotics induced by calcium entry blockers in cultured cardiomyocytes. Toxicol Appl Pharmacol. 1991; 108:140-9.
129. Akimoto H, Bruno NA, Slate DL, Billingham ME, Torti SV, Torti FM. Effect of verapamil on doxorubicin cardiotoxicity: altered muscle gene expression in cultured neonatal rat cardiomyocytes. Cancer Res. 1993; 53:4658-64.
130. Milei J, Marantz A, Ale J, Vazquez A, Buceta JE. Prevention of adriamycin-induced cardiotoxicity by prenylamine: a pilot double blind study. Cancer Drug Deliv. 1987; 4:129-36.
131. Fu LX, Bergh CH, Hoebeke J, Liang QM, Sjogren KG, Waagstein F, et al. Effect of metoprolol on activity of ß-adrenoceptor coupled to guanine nucleotide binding regulatory proteins in adriamycin-induced cardiotoxicity. Basic Res Cardiol. 1991; 86:117-26.
132. Mak IT, Weglicki WB. Protection by ß-blocking agents against free radical-mediated sarcolemmal lipid peroxidation. Circ Res. 1988; 63:262-6.
133. Kramer JH, Mak IT, Freedman AM, Weglicki WB. Propranolol reduces anoxia/reoxygenation-mediated injury of adult myocytes through an antiradical mechanism. J Mol Cell Cardiol. 1991; 23:1231-44.
134. Liu XK, Engelman RM, Agrawal HR, Das DK. Preservation of membrane phospholipids by propranolol, pindolol, and metoprolol: a novel mechanism of action of ß-blockers. J Mol Cell Cardiol. 1991; 23:1091-100.
135. Shaddy RE, Olsen SL, Bristow MR, Taylor DO, Bullock EA, Tani LY, et al. Efficacy and safety of metoprolol in the treatment of doxorubicin-induced cardiomyopathy in pediatric patients. Am Heart J. 1995:129; 197-9.
136. Waagstein F, Bristow MR, Swedberg K, Camerini F, Fowler MB, Silver MA, et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group. Lancet. 1993; 342:1441-6.
137. Fisher ML, Gottlieb SS, Plotnick GD, Greenberg NL, Patten RD, Bennett SK, et al. Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial. J Am Coll Cardiol. 1994; 23:943-50.
138. Bleyer WA. The impact of childhood cancer in the United States and the world. CA Cancer J Clin. 1990; 40:355-67.
139. Wingo PA, Tong T, Bolden S. Cancer statistics, 1995. CA Cancer J Clin. 1995; 45:8-30.
140. "Effect of enalapril on survival in patients with reduced left ventricular fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med. 1991; 325:293-302.".
141. Gaasch WH. Diagnosis and treatment of heart failure based on left ventricular systolic or diastolic dysfunction. JAMA. 1994; 271:1276-80.
142. Dorent R, Pavie A, Nataf P, Tedy G, Vaissier E, Ghoussoub JJ, et al. Heart transplantation is a valid therapeutic option for anthracycline cardiomyopathy. Transplant Proc. 1995; 27:1683.
143. Armitage JM, Kormos RL, Griffith BP, Fricker FJ, Hardesty RL. Heart transplantation in patients with malignant disease. J Heart Transplant. 1990; 9:627-9.
144. Edwards BS, Hunt SA, Fowler MB, Valantine HA, Stinson EB, Schroeder JS. Cardiac transplantation in patients with preexisting neoplastic diseases. Am J Cardiol. 1990; 65:501-4.
145. Lee TH, Goldman L. Development and analysis of observational data bases. J Am Coll Cardiol. 1989:14:44A-7A.
146. Diamond GA. Future imperfect: the limitations of clinical prediction models and the limits of clinical prediction. J Am Coll Cardiol. 1989; 14:12A-22A.
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 P. Venkatesh, B. Shantala, G. C. Jagetia, K. K. Rao, and M. S. Baliga Modulation of Doxorubicin-Induced Genotoxicity by Aegle marmelos in Mouse Bone Marrow: A Micronucleus Study Integr Cancer Ther, March 1, 2007; 6(1): 42 - 53. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Cardinale, A. Colombo, M. T. Sandri, G. Lamantia, N. Colombo, M. Civelli, G. Martinelli, F. Veglia, C. Fiorentini, and C. M. Cipolla Prevention of High-Dose Chemotherapy-Induced Cardiotoxicity in High-Risk Patients by Angiotensin-Converting Enzyme Inhibition Circulation, December 5, 2006; 114(23): 2474 - 2481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Piekarz, A. R. Frye, J. J. Wright, S. M. Steinberg, D. J. Liewehr, D. R. Rosing, V. Sachdev, T. Fojo, and S. E. Bates Cardiac Studies in Patients Treated with Depsipeptide, FK228, in a Phase II Trial for T-Cell Lymphoma. Clin. Cancer Res., June 15, 2006; 12(12): 3762 - 3773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Combs, N. Neil, and D. M. Aboulafia Liposomal Doxorubicin, Cyclophosphamide, and Etoposide and Antiretroviral Therapy for Patients with AIDS-Related Lymphoma: A Pilot Study. Oncologist, June 1, 2006; 11(6): 666 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Horan, M. F. McMullin, and P. P. McKeown Anthracycline cardiotoxicity Eur. Heart J., May 2, 2006; 27(10): 1137 - 1138. [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Moser, E. M. Noordijk, F. E. van Leeuwen, S. le Cessie, J. W. Baars, J. Thomas, P. Carde, J. H. Meerwaldt, M. van Glabbeke, and H. C. Kluin-Nelemans Long-term risk of cardiovascular disease after treatment for aggressive non-Hodgkin lymphoma Blood, April 1, 2006; 107(7): 2912 - 2919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tassan-Mangina, D. Codorean, M. Metivier, B. Costa, C. Himberlin, C. Jouannaud, A. M. Blaise, J. Elaerts, and P. Nazeyrollas Tissue Doppler imaging and conventional echocardiography after anthracycline treatment in adults: Early and late alterations of left ventricular function during a prospective study Eur J Echocardiogr, March 1, 2006; 7(2): 141 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Spallarossa, P. Altieri, S. Garibaldi, G. Ghigliotti, C. Barisione, V. Manca, P. Fabbi, A. Ballestrero, C. Brunelli, and A. Barsotti Matrix metalloproteinase-2 and -9 are induced differently by doxorubicin in H9c2 cells: The role of MAP kinases and NAD(P)H oxidase Cardiovasc Res, February 15, 2006; 69(3): 736 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E De Caro, F Fioredda, M G Calevo, A Smeraldi, M Saitta, G Hanau, M Faraci, F Grisolia, G Dini, G Pongiglione, et al. Exercise capacity in apparently healthy survivors of cancer Arch. Dis. Child., January 1, 2006; 91(1): 47 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wojnowski, B. Kulle, M. Schirmer, G. Schluter, A. Schmidt, A. Rosenberger, S. Vonhof, H. Bickeboller, M. R. Toliat, E.-K. Suk, et al. NAD(P)H Oxidase and Multidrug Resistance Protein Genetic Polymorphisms Are Associated With Doxorubicin-Induced Cardiotoxicity Circulation, December 13, 2005; 112(24): 3754 - 3762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Doyle, A. I. Neugut, J. S. Jacobson, V. R. Grann, and D. L. Hershman Chemotherapy and Cardiotoxicity in Older Breast Cancer Patients: A Population-Based Study J. Clin. Oncol., December 1, 2005; 23(34): 8597 - 8605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Mrozek, C. A. Rhoades, J. Allen, E. M. Hade, and C. L. Shapiro Phase I trial of liposomal encapsulated doxorubicin (MyocetTM; D-99) and weekly docetaxel in advanced breast cancer patients Ann. Onc., July 1, 2005; 16(7): 1087 - 1093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Hayek, E. Speakman, and E. Rehmus Acute Doxorubicin Cardiotoxicity N. Engl. J. Med., June 9, 2005; 352(23): 2456 - 2457. [Full Text] [PDF]
|
|
|
|
|
|
S. Kilickap, I. Barista, E. Akgul, K. Aytemir, S. Aksoyek, S. Aksoy, I. Celik, S. Kes, and G. Tekuzman cTnT can be a useful marker for early detection of anthracycline cardiotoxicity Ann. Onc., May 1, 2005; 16(5): 798 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pentheroudakis and N. Pavlidis Juvenile cancer: improving care for adolescents and young adults within the frame of medical oncology Ann. Onc., February 1, 2005; 16(2): 181 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kilickap, E. Akgul, S. Aksoy, K. Aytemir, and I. Barista Doxorubicin-induced second degree and complete atrioventricular block Europace, January 1, 2005; 7(3): 227 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chan, N. Davidson, E. Juozaityte, F. Erdkamp, A. Pluzanska, N. Azarnia, and L. W. Lee Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer Ann. Onc., October 1, 2004; 15(10): 1527 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Briasoulis, G. Pentheroudakis, V. Karavasilis, E. Tzamakou, D. Rammou, and N. Pavlidis Weekly paclitaxel combined with pegylated liposomal doxorubicin (CaelyxTM) given every 4 weeks: dose-finding and pharmacokinetic study in patients with advanced solid tumors Ann. Onc., October 1, 2004; 15(10): 1566 - 1573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Perez, V. J. Suman, N. E. Davidson, P. A. Kaufman, S. Martino, S. R. Dakhil, J. N. Ingle, R. J. Rodeheffer, B. J. Gersh, and A. S. Jaffe Effect of Doxorubicin Plus Cyclophosphamide on Left Ventricular Ejection Fraction in Patients With Breast Cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial J. Clin. Oncol., September 15, 2004; 22(18): 3700 - 3704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I. Jung, H. H. Kim, S. H. Park, S. W. Song, M. H. Chung, H. S. Kim, K. J. Kim, M. I. Ahn, S. B. Seo, and S. T. Hahn Thoracic Manifestations of Breast Cancer and Its Therapy RadioGraphics, September 1, 2004; 24(5): 1269 - 1285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Cardinale, M. T. Sandri, A. Colombo, N. Colombo, M. Boeri, G. Lamantia, M. Civelli, F. Peccatori, G. Martinelli, C. Fiorentini, et al. Prognostic Value of Troponin I in Cardiac Risk Stratification of Cancer Patients Undergoing High-Dose Chemotherapy Circulation, June 8, 2004; 109(22): 2749 - 2754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Hequet, Q.H. Le, I. Moullet, E. Pauli, G. Salles, D. Espinouse, C. Dumontet, C. Thieblemont, P. Arnaud, D. Antal, et al. Subclinical Late Cardiomyopathy After Doxorubicin Therapy for Lymphoma in Adults J. Clin. Oncol., May 15, 2004; 22(10): 1864 - 1871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H.B. Wu, M. Packer, A. Smith, R. Bijou, D. Fink, J. Mair, L. Wallentin, N. Johnston, C. S. Feldcamp, D. M. Haverstick, et al. Analytical and Clinical Evaluation of the Bayer ADVIA Centaur Automated B-Type Natriuretic Peptide Assay in Patients with Heart Failure: A Multisite Study Clin. Chem., May 1, 2004; 50(5): 867 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Van Mieghem, M. Sabbe, and D. Knockaert The Clinical Value of the ECG in Noncardiac Conditions Chest, April 1, 2004; 125(4): 1561 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kattlove and R. J. Winn Ongoing Care of Patients After Primary Treatment for Their Cancer CA Cancer J Clin, May 1, 2003; 53(3): 172 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Limat, K. Demesmay, L. Voillat, Y. Bernard, E. Deconinck, A. Brion, A. Sabbah, M. C. Woronoff-Lemsi, and J. Y. Cahn Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin's lymphoma Ann. Onc., February 1, 2003; 14(2): 277 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kim, H. Sikder, and K. K. Singh A colony color method identifies the vulnerability of mitochondria to oxidative damage Mutagenesis, September 1, 2002; 17(5): 375 - 381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Childs, S. L. Phaneuf, A. J. Dirks, T. Phillips, and C. Leeuwenburgh Doxorubicin Treatment in Vivo Causes Cytochrome c Release and Cardiomyocyte Apoptosis, As Well As Increased Mitochondrial Efficiency, Superoxide Dismutase Activity, and Bcl-2:Bax Ratio Cancer Res., August 15, 2002; 62(16): 4592 - 4598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M T Meinardi, W T A van der Graaf, J A Gietema, M P van den Berg, D T Sleijfer, E G E de Vries, J Haaksma, F Boomsma, and D J van Veldhuisen Evaluation of long term cardiotoxicity after epirubicin containing adjuvant chemotherapy and locoregional radiotherapy for breast cancer using various detection techniques Heart, July 1, 2002; 88(1): 81 - 82. [Full Text] [PDF]
|
|
|
|
 |
|
 M.I. Gharib and A.K. Burnett Chemotherapy-induced cardiotoxicity: current practice and prospects of prophylaxis Eur J Heart Fail, June 1, 2002; 4(3): 235 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. V. Jensen, T. Skovsgaard, and S. L. Nielsen Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients Ann. Onc., May 1, 2002; 13(5): 699 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nakamura, H. Sugumi, A. Yamaguchi, T. Uenaka, Y. Kotake, T. Okada, J. Kamata, J. Niijima, T. Nagasu, N. Koyanagi, et al. Antitumor Activity of ER-37328, a Novel Carbazole Topoisomerase II Inhibitor Mol. Cancer Ther., January 1, 2002; 1(3): 169 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Levade, N. Auge, R. J. Veldman, O. Cuvillier, A. Negre-Salvayre, and R. Salvayre Sphingolipid Mediators in Cardiovascular Cell Biology and Pathology Circ. Res., November 23, 2001; 89(11): 957 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Shapiro and A. Recht Side Effects of Adjuvant Treatment of Breast Cancer N. Engl. J. Med., June 28, 2001; 344(26): 1997 - 2008. [Full Text] [PDF]
|
|
|
|
 |
|
 W. Darko, A. L Smith, E. L King, and S. J Grethlein Mitoxantrone-induced cardiotoxicity Journal of Oncology Pharmacy Practice, March 1, 2001; 7(1): 47 - 48. [Abstract] [PDF]
|
|
|
|
|
|
C. Geroni, M. Ripamonti, C. Arrigoni, F. Fiorentini, L. Capolongo, D. Moneta, S. Marchini, P. D. Torre, C. Albanese, M. G. Lamparelli, et al. Pharmacological and Toxicological Aspects of 4-Demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin (PNU-159548): A Novel Antineoplastic Agent Cancer Res., March 1, 2001; 61(5): 1983 - 1990. [Abstract] [Full Text]
|
|
|
|
|
|
M. Zambetti, A. Moliterni, C. Materazzo, M. Stefanelli, S. Cipriani, P. Valagussa, G. Bonadonna, and L. Gianni Long-Term Cardiac Sequelae in Operable Breast Cancer Patients Given Adjuvant Chemotherapy With or Without Doxorubicin and Breast Irradiation J. Clin. Oncol., January 1, 2001; 19(1): 37 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C.M. Kremer, E. C. van Dalen, M. Offringa, J. Ottenkamp, and P. A. Voute Anthracycline-Induced Clinical Heart Failure in a Cohort of 607 Children: Long-Term Follow-Up Study J. Clin. Oncol., January 1, 2001; 19(1): 191 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Burstein and E. P. Winer Primary Care for Survivors of Breast Cancer N. Engl. J. Med., October 12, 2000; 343(15): 1086 - 1094. [Full Text] [PDF]
|
|
|
|
|
|
G. L. Forrest, B. Gonzalez, W. Tseng, X. Li, and J. Mann Human Carbonyl Reductase Overexpression in the Heart Advances the Development of Doxorubicin-induced Cardiotoxicity in Transgenic Mice Cancer Res., September 1, 2000; 60(18): 5158 - 5164. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. Kimura, I. Fujita, N. Itoh, N. Muto, T. Nakanishi, K. Takahashi, J. Azuma, and K. Tanaka Metallothionein Acts as a Cytoprotectant against Doxorubicin Toxicity J. Pharmacol. Exp. Ther., January 1, 2000; 292(1): 299 - 302. [Abstract] [Full Text]
|
|
|
|
|
|
T. W. Cheung, S. C. Remick, N. Azarnia, J. A. Proper, J. R. Barrueco, and B. J. Dezube AIDS-related Kaposi's Sarcoma: A Phase II Study of Liposomal Doxorubicin Clin. Cancer Res., November 1, 1999; 5(11): 3432 - 3437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Cobleigh, C. L. Vogel, D. Tripathy, N. J. Robert, S. Scholl, L. Fehrenbacher, J. M. Wolter, V. Paton, S. Shak, G. Lieberman, et al. Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease J. Clin. Oncol., September 1, 1999; 17(9): 2639 - 2639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. ANDRIEU-ABADIE, J.-P. JAFFRÉZOU, S. HATEM, G. LAURENT, T. LEVADE, and J.-J. MERCADIER L-carnitine prevents doxorubicin-induced apoptosis of cardiac myocytes: role of inhibition of ceramide generation FASEB J, September 1, 1999; 13(12): 1501 - 1510. [Abstract] [Full Text]
|
|
|
|
|
|
E. Delpy, S. N Hatem, N. Andrieu, C. de Vaumas, M. Henaff, C. Rucker-Martin, J.-P. Jaffrezou, G. Laurent, T. Levade, and J.-J. Mercadier Doxorubicin induces slow ceramide accumulation and late apoptosis in cultured adult rat ventricular myocytes Cardiovasc Res, August 1, 1999; 43(2): 398 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Hashimoto, F. Ichida, M. Miura, T. Okabe, H. Kanegane, K.-i. Uese, Y. Hamamichi, T. Misaki, S. Koizumi, and T. Miyawaki Automatic Border Detection Identifies Subclinical Anthracycline Cardiotoxicity in Children With Malignancy Circulation, May 11, 1999; 99(18): 2367 - 2370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Valero, A. U. Buzdar, R. L. Theriault, N. Azarnia, G. A. Fonseca, J. Willey, M. Ewer, R. S. Walters, B. Mackay, D. Podoloff, et al. Phase II Trial of Liposome-Encapsulated Doxorubicin, Cyclophosphamide, and Fluorouracil as First-Line Therapy in Patients With Metastatic Breast Cancer J. Clin. Oncol., May 1, 1999; 17(5): 1425 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Shapiro, T. Ervin, L. Welles, N. Azarnia, J. Keating, and D. F. Hayes Phase II Trial of High-Dose Liposome-Encapsulated Doxorubicin With Granulocyte Colony-Stimulating Factor in Metastatic Breast Cancer J. Clin. Oncol., April 1, 1999; 17(5): 1435 - 1435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Saadane, L. Alpert, and L. E. Chalifour TAFII250, Egr-1, and D-type cyclin expression in mice and neonatal rat cardiomyocytes treated with doxorubicin Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H803 - H814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Lipshultz, M. A. Grenier, S. D. Colan, A. D. Ginsburg, S. M. Swain, F. M. Muggia, J. L. Speyer, P. K. Singal, C. L.M. Olweny, and T. Li Doxorubicin-Induced Cardiomyopathy N. Engl. J. Med., February 25, 1999; 340(8): 653 - 655. [Full Text]
|
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