Search

Background: This review update has been managed by both the Childhood Cancer and Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Groups.The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. To prevent this cardiotoxicity, different anthracycline dosage schedules have been studied., Objectives: To determine the occurrence of cardiotoxicity with the use of different anthracycline dosage schedules (that is peak doses and infusion durations) in people with cancer., Search Methods: We searched the databases of the Cochrane Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 11, 2015), MEDLINE (1966 to December 2015), and EMBASE (1980 to December 2015). We also searched reference lists of relevant articles, conference proceedings, experts in the field, and ongoing trials databases., Selection Criteria: Randomised controlled trials (RCTs) in which different anthracycline dosage schedules were compared in people with cancer (children and adults)., Data Collection and Analysis: Two review authors independently performed the study selection, the 'Risk of bias' assessment, and data extraction. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions., Main Results: We identified 11 studies: 7 evaluated different infusion durations (803 participants), and 4 evaluated different peak doses (5280 participants). Seven studies were RCTs addressing different anthracycline infusion durations; we identified long-term follow-up data for one of the trials in this update. The meta-analysis showed a statistically significant lower rate of clinical heart failure with an infusion duration of six hours or longer as compared to a shorter infusion duration (risk ratio (RR) 0.27; 95% confidence interval 0.09 to 0.81; 5 studies; 557 participants). The majority of participants included in these studies were adults with different solid tumours. For different anthracycline peak doses, we identified two RCTs addressing a doxorubicin peak dose of less than 60 mg/m(2) versus 60 mg/m(2) or more, one RCT addressing a liposomal doxorubicin peak dose of 25 mg/m(2) versus 50 mg/m(2), and one RCT addressing an epirubicin peak dose of 83 mg/m(2) versus 110 mg/m(2). A significant difference in the occurrence of clinical heart failure was identified in none of the studies. The participants included in these studies were adults with different solid tumours. High or unclear 'Risk of bias' issues were present in all studies., Authors' Conclusions: An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure, and it seems to reduce the risk of subclinical cardiac damage. Since there is only a small amount of data for children and data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children.We identified no significant difference in the occurrence of clinical heart failure in participants treated with a doxorubicin peak dose of less than 60 mg/m(2) or 60 mg/m(2) or more. Only one RCT was available for the other identified peak doses, so we can make no definitive conclusions about the occurrence of cardiotoxicity. More high-quality research is needed, both in children and adults and in leukaemias and solid tumours.

Background: The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied., Objectives: To determine the occurrence of cardiotoxicity with the use of different anthracycline derivates in cancer patients., Search Strategy: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 to 29 May 2009) and EMBASE (1980 to 2 June 2009). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing-trials-databases., Selection Criteria: Randomised controlled trials (RCTs) in which different anthracycline derivates were compared in cancer patients (children and adults)., Data Collection and Analysis: Two authors independently performed study selection, assessment of risk of bias and data-extraction including adverse effects., Main Results: We identified five RCTs of varying quality addressing epirubicin versus doxorubicin (1036 patients) with the same dose. The meta-analysis showed no evidence for a significant difference in the occurrence of clinical heart failure between the treatment groups (RR = 0.36, 95% CI 0.12 to 1.11). However, there is some suggestion of a lower rate of clinical heart failure in patients treated with epirubicin.We identified two RCTs with varying quality addressing liposomal-encapsulated doxorubicin versus conventional doxorubicin (521 patients). The meta-analysis showed a significantly lower rate of both clinical heart failure and clinical and subclinical heart failure combined in patients treated with liposomal-encapsulated doxorubicin (RR = 0.20, 95% CI 0.05 to 0.75 and RR = 0.38, 95% CI 0.24 to 0.59 respectively). It should be noted that in one of the studies patients in the liposomal-encapsulated doxorubicin group received a higher cumulative anthracycline dose than patients in the doxorubicin group.For the other possible combinations of different anthracycline derivates only one RCT (epirubicin versus liposomal-encapsulated doxorubicin) or no RCT was identified., Authors' Conclusions: We are not able to favour either epirubicin or doxorubicin when given with the same dose. Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin. For both epirubicin versus doxorubicin and liposomal-encapsulated doxorubicin versus conventional doxorubicin no conclusions can be made about the effects of treatment in children treated with anthracyclines and also not in patients diagnosed with leukaemia. More research is needed. For other combinations of anthracycline derivates not enough evidence was available to make definitive conclusions about the occurrence of cardiotoxicity in patients treated with anthracyclines.

Background: The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied., Objectives: To determine the occurrence of cardiotoxicity with the use of different anthracycline derivates in cancer patients., Search Strategy: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 to 29 May 2009) and EMBASE (1980 to 2 June 2009). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing-trials-databases., Selection Criteria: Randomised controlled trials (RCTs) in which different anthracycline derivates were compared in cancer patients (children and adults)., Data Collection and Analysis: Two authors independently performed study selection, assessment of risk of bias and data-extraction including adverse effects., Main Results: We identified five RCTs of varying quality addressing epirubicin versus doxorubicin (1036 patients) with the same dose. The meta-analysis showed no evidence for a significant difference in the occurrence of clinical heart failure between the treatment groups (RR = 0.36, 95% CI 0.12 to 1.11). However, there is some suggestion of a lower rate of clinical heart failure in patients treated with epirubicin.We identified two RCTs with varying quality addressing liposomal-encapsulated doxorubicin versus conventional doxorubicin (521 patients). The meta-analysis showed a significantly lower rate of both clinical heart failure and clinical and subclinical heart failure combined in patients treated with liposomal-encapsulated doxorubicin (RR = 0.20, 95% CI 0.05 to 0.75 and RR = 0.38, 95% CI 0.24 to 0.59 respectively). It should be noted that in one of the studies patients in the liposomal-encapsulated doxorubicin group received a higher cumulative anthracycline dose than patients in the doxorubicin group.For the other possible combinations of different anthracycline derivates only one RCT (epirubicin versus liposomal-encapsulated doxorubicin) or no RCT was identified., Authors' Conclusions: We are not able to favour either epirubicin or doxorubicin when given with the same dose. Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin. For both epirubicin versus doxorubicin and liposomal-encapsulated doxorubicin versus conventional doxorubicin no conclusions can be made about the effects of treatment in children treated with anthracyclines and also not in patients diagnosed with leukaemia. More research is needed. For other combinations of anthracycline derivates not enough evidence was available to make definitive conclusions about the occurrence of cardiotoxicity in patients treated with anthracyclines.

Background: The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. To prevent this cardiotoxicity, different anthracycline dosage schedules have been studied., Objectives: To determine the occurrence of cardiotoxicity with the use of different anthracycline dosage schedules (i.e. peak doses and infusion durations) in cancer patients., Search Strategy: We searched the databases of The Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2008), MEDLINE (1966 to November 2008) and EMBASE (1980 to November 2008). Also, we searched reference lists of relevant articles, conference proceedings and ongoing trials databases., Selection Criteria: Randomised controlled trials (RCTs) in which different anthracycline dosage schedules were compared in cancer patients (children and adults)., Data Collection and Analysis: Two authors independently performed the study selection, the risk of bias assessment and the data-extraction., Main Results: We identified seven RCTs addressing different anthracycline infusion durations. The meta-analysis showed a statistically significant lower rate of clinical heart failure with an infusion duration of 6 hours or longer as compared to a shorter infusion duration (relative risk (RR) = 0.27; 95% confidence interval (CI) 0.09 to 0.81; 5 studies; 557 patients). The majority of patients included in these studies were adults with different solid tumours. For different anthracycline peak doses we identified two RCTs addressing a doxorubicin peak dose of less than 60 mg/m(2) versus 60 mg/m(2) or more, one RCT addressing a liposomal doxorubicin peak dose of 25 mg/m(2) versus 50 mg/m(2) and one RCT addressing an epirubicin peak dose of 83 mg/m(2) versus 110 mg/m(2). In none of the studies a significant difference in the occurrence of clinical heart failure was identified. All patients included in these studies were adults with different solid tumours., Authors' Conclusions: An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure and it seems to reduce the risk of subclinical cardiac damage. Since there is only a small amount of data for children and data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children.No significant difference in the occurrence of clinical heart failure was identified in patients treated with a doxorubicin peak dose of less than 60 mg/m(2) or 60 mg/m(2) or more. For the other identified peak doses only one RCT was available, so no definitive conclusions can be made about the occurrence of cardiotoxicity. More high quality research is needed, both in children and adults and in leukaemias and solid tumours.

Background: The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied., Objectives: The primary objective was to determine the occurrence of cardiotoxicity with the use of different anthracycline derivates in cancer patients., Search Strategy: We searched the databases of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2005), MEDLINE (1966 to April 2005) and EMBASE (1980 to April 2005). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trials databases., Selection Criteria: Randomised controlled trials (RCTs) in which different anthracycline derivates were compared in cancer patients (children and adults)., Data Collection and Analysis: Two authors independently performed the study selection, quality assessment and data-extraction including adverse effects., Main Results: We identified five RCTs of varying quality addressing epirubicin versus doxorubicin (1036 patients) with the same dose. The meta-analysis showed no evidence for a significant difference in the occurrence of clinical heart failure between the treatment groups (RR = 0.36, 95% CI 0.12 to 1.11). However, there is some suggestion of a lower rate of clinical heart failure in patients treated with epirubicin. We identified two RCTs with varying quality addressing liposomal-encapsulated doxorubicin versus conventional doxorubicin (521 patients). The meta-analysis showed a significantly lower rate of both clinical heart failure and clinical and subclinical heart failure combined in patients treated with liposomal-encapsulated doxorubicin (RR = 0.20, 95% CI 0.05 to 0.75 and RR = 0.38, 95% CI 0.24 to 0.59 respectively). It should be noted that in one of the studies patients in the liposomal-encapsulated doxorubicin group received a higher cumulative anthracycline dose than patients in the doxorubicin group. For the other possible combinations of different anthracycline derivates only one RCT was identified., Authors' Conclusions: We are not able to favour either epirubicin or doxorubicin when given with the same dose. Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin. For both epirubicin versus doxorubicin and liposomal-encapsulated doxorubicin versus conventional doxorubicin no conclusions can be made about the effects of treatment in children treated with anthracyclines and also not in patients diagnosed with leukaemia. More research is needed. For other combinations of anthracycline derivates not enough evidence was available to make definitive conclusions about the occurrence of cardiotoxicity in patients treated with anthracyclines.

Background: The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline dosage schedules (i.e. peak doses and infusion durations) have been studied., Objectives: The primary objective was to determine the occurrence of cardiotoxicity with the use of different anthracycline dosage schedules in cancer patients., Search Strategy: We searched the databases of The Cochrane Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to June 2004) and EMBASE (1980 to June 2004). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trials databases., Selection Criteria: Randomised controlled trials (RCTs) in which different anthracycline dosage schedules were compared in cancer patients (children and adults)., Data Collection and Analysis: Two authors independently performed the study selection, quality assessment and data-extraction including adverse effects., Main Results: We identified six RCTs of varying quality addressing different anthracycline infusion durations (625 patients). The meta-analysis showed a statistically significant lower rate of clinical heart failure with an infusion duration of 6 hours or longer as compared to a shorter infusion duration, i.e. maximal duration of 1 hour (RR = 0.27; 95% confidence interval (CI) 0.09 to 0.81; 5 studies; 557 patients). In individual studies the infusion duration of 6 hours or longer also seemed to reduce the risk of subclinical cardiac damage. No statistically significant difference in response rate was found (RR = 0.83; 95% CI 0.45 to 1.54; 2 studies; 292 patients). No statistically significant difference in overall survival was found (HR = 1,42; 95% CI 0.61 to 3.30; 2 studies; 322 patients), but there was unexplained heterogeneity (I(2)=75%). No conclusions can be made regarding adverse effects. It should be emphasised that the majority of patients included in these studies were adults with different solid tumours. Children with leukaemia could not be included in the performed meta-analyses, but they were included in the descriptive results of non-pooled studies. No RCTs addressing different anthracycline peak doses with the same cumulative anthracycline dose in both treatment groups were identified., Authors' Conclusions: An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure, and it seems to reduce the risk of subclinical cardiac damage. There is no evidence which suggests a difference in response rate and survival between both treatment groups. Since there is only a small amount of data for children and also because data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children. For different anthracycline peak doses no high quality evidence was available and therefore, no definitive conclusions can be made about the occurrence of cardiotoxicity in patients treated with different anthracycline peak doses.

Over the last 40 years, great progress has been made in treating childhood and adult cancers. However, this progress has come at an unforeseen cost, in the form of emerging long-term effects of anthracycline treatment. A major complication of anthracycline therapy is its adverse cardiovascular effects. If these cardiac complications could be reduced or prevented, higher doses of anthracyclines could potentially be used, thereby further increasing cancer cure rates. Moreover, as the incidence of cardiac toxicity resulting in congestive heart failure or even heart transplantation dropped, the quality and extent of life for cancer survivors would improve. We review the proposed mechanisms of action of anthracyclines and the consequences associated with anthracycline treatment in children and adults. We summarise the most promising current strategies to limit or prevent anthracycline-induced cardiotoxicity, as well as possible strategies to prevent existing cardiomyopathy from worsening.

Asymptomatic anthracycline-induced cardiac damage (A-CD) is a serious problem among young childhood cancer survivors. The aim of this survey was to assess the current treatment policy in these patients in the Netherlands. A questionnaire was sent to all 136 departments of adult or pediatric cardiology in the Netherlands. It was returned by 61% of the departments. Sixty-six percent of the respondents started medical treatment (ie, an ACE inhibitor and/or a beta-blocker) in childhood cancer survivors with asymptomatic A-CD. Fifty-eight percent of the respondents indicated that their treatment decision was based on published findings in the literature, but none of them referred to studies evaluating the treatment of asymptomatic A-CD. A majority of adult and pediatric cardiologists started medical treatment in childhood cancer survivors with asymptomatic A-CD without knowledge of the benefits and risks of treatment in this patient group. Before ACE inhibitors and/or beta-blockers can be recommended as routine practice in childhood cancer survivors with asymptomatic A-CD, randomized controlled trials should be performed. Until then, the authors recommend centralizing the treatment of childhood cancer survivors with asymptomatic A-CD in a specialized center to cluster the available knowledge and experience.

Purpose: To determine the value of indium-111-antimyosin ((111)In-AM) scintigraphy in the early detection of myocardial damage in children treated with doxorubicin., Patients and Methods: Twelve planar scintigrams were made of eight patients (seven children and one young adult; mean age, 12 years). Three scans were obtained before doxorubicin therapy in three patients, and nine scans were obtained during doxorubicin therapy in seven patients. The heart-to-lung ratio (HLR) was calculated. Left ventricular function was assessed by echocardiography before and during therapy by measuring the fractional shortening (FS)., Results: The HLR of the three baseline scans was below 1.5, within the normal range for adults. Six of the seven patients whose scans were obtained during chemotherapy had abnormal HLR values (> 1.5). One patient had severe myocyte damage and showed an early increase in the HLR (2.3) after a cumulative doxorubicin dose of 150 mg/m(2). The FS measured by echocardiography was normal throughout therapy, and the final cumulative dose of doxorubicin was 450 mg/m(2). This patient developed fatal clinical heart failure 3 months after completion of chemotherapy. In one patient, who was pretreated with the cardioprotective agent dexrazoxane, the HLR remained within normal limits during therapy., Conclusion: (111)In-AM scintigraphy seems to be suitable to detect early myocardial damage after a cumulative doxorubicin dose of 150 mg/m(2 )in children and may be useful for identifying children who are at increased risk of developing cardiac sequelae.