Cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review

Bryant, Jackie; Picot, Joanna; Levitt, G.; Sullivan, Ian D.; Baxter, Laurence A.; Clegg, Andrew

doi:10.3310/hta11270

Cited by 49 publications

(32 citation statements)

References 27 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There is no agreement on the optimal method to assess and no standardization of reporting or outcome measures in studies of cardioprotection during anthracycline use. 6 Lipshultz et al 4 described the use of cardiac troponin T as a sensitive and specific marker of early myocardial injury was superior to echocardiography in children with ALL. The measure of troponin T levels is not available in every clinical setting.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Dexrazoxane for Clinical and Subclinical Cardiotoxicity in Children With Acute Myeloid Leukemia

Sánchez-Medina

González-Ramella²,

Gallegos-Castorena³

2010

Journal of Pediatric Hematology/Oncology

View full text Add to dashboard Cite

Cardiotoxicity is frequently present with anthracycline treatment. Most acute myeloid leukemia (AML) protocols use anthracyclines. Dexrazoxane has cardioprotective activity. The aim of this study was to evaluate cardioprotection of dexrazoxane in a prospective study. Fifty pediatric AML patients were treated with a Medical Research Council AML 10 modified protocol with dexrazoxane previous to any anthracycline dose. Cardiac function was evaluated at diagnosis, before every cycle, and every 6 months after the end of chemotherapy. Accumulative doses of anthracycline reached 424 mg/m (150 to 850 mg/m). Forty-eight patients (96%) received a dose higher than 300 mg/m. Twenty-eight percent had a grade of cardiotoxicity (24% grade 1 and 4% grade 2). Non 3 or 4 grade cardiotoxicity was seen. Cumulated anthracycline doses did not correlated with cardiotoxicity (P=0.815). The event-free survival was 53%, 15.7% died of disease, and 11.8% died free of leukemia. There is still not an agreement for the optimal method to reduce cardiotoxicity in children receiving anthracyclines. In our study, we could conclude that the use of dexrazoxane was effective cardioprotectant to allow a high-dose of anthracycline therapy. A randomized study is necessary to consolidate this asseveration.

show abstract

Section: Discussionmentioning

confidence: 99%

The Effect of Dexrazoxane for Clinical and Subclinical Cardiotoxicity in Children With Acute Myeloid Leukemia

Sánchez-Medina

González-Ramella²,

Gallegos-Castorena³

2010

Journal of Pediatric Hematology/Oncology

View full text Add to dashboard Cite

show abstract

“…The potential long-term cardiac risk that results from anthracycline-containing chemotherapy is relatively wellstudied in children, 39 but it is less well-studied in adult patients with cancer, particularly in the elderly population. Our study sought to examine whether anthracyclinebased or nonanthracycline-based chemotherapy is Original Article…”

Section: Discussionmentioning

confidence: 99%

Cardiac toxicity associated with anthracycline‐containing chemotherapy in older women with breast cancer

Xia

Liu

et al. 2009

Cancer

View full text Add to dashboard Cite

Objective To identify the autoantigen recognized by the autoantibody that is associated with clinically amyopathic dermatomyositis (C‐ADM) and rapidly progressive interstitial lung disease (ILD). Methods An anti–CADM‐140 antibody–positive prototype serum sample was used to screen a HeLa cell–derived complementary DNA (cDNA) library. Selected cDNA clones were further evaluated by immunoprecipitation of their in vitro–transcribed and in vitro–translated products using anti–CADM‐140 antibody–positive and anti‐CADM‐140 antibody–negative sera. The lysates of COS‐7 cells transfected with the putative antigen were similarly tested. An enzyme‐linked immunosorbent assay (ELISA) to detect the anti–CADM‐140 antibody was established using a recombinant CADM‐140 antigen, and its specificity and sensitivity for C‐ADM and rapidly progressive ILD were assessed in 294 patients with various connective tissue diseases. Results By cDNA library screening and immunoprecipitation of in vitro–transcribed and in vitro–translated products, we obtained a cDNA clone encoding melanoma differentiation–associated gene 5 (MDA‐5). The anti–CADM‐140 antibodies in patients' sera specifically reacted with MDA‐5 protein expressed in cells transfected with full‐length MDA‐5 cDNA, confirming the identity of MDA‐5 as the CADM‐140 autoantigen. The ELISA, using recombinant MDA‐5 protein as the antigen, showed an analytical sensitivity of 85% and analytical specificity of 100%, in comparison with the “gold standard” immunoprecipitation assay, and was useful for identifying patients with C‐ADM and/or rapidly progressive ILD. Conclusion Given that RNA helicase encoded by MDA‐5 is a critical molecule involved in the innate immune defense against viruses, viral infection may play an important role in the pathogenesis of C‐ADM and rapidly progressive ILD. Moreover, our ELISA using recombinant MDA‐5 protein makes detection of the anti–CADM‐140 antibody routinely available.

show abstract

“…1 However, cardiomyopathy is a dose-limiting complication; cardiac abnormalities develop in up to 60% of patients exposed to high doses of anthracyclines. 2 The dose-dependent increase in cardiomyopathy risk [3][4][5] is modified by younger age at exposure and chest radiation. 6 However, doses as low as 150 mg/m 2 result in cardiomyopathy in some patients, 3 suggesting a role for interindividual variability in anthracycline pharmacodynamics.…”

Section: Introductionmentioning

confidence: 99%

Anthracycline-Related Cardiomyopathy After Childhood Cancer: Role of Polymorphisms in Carbonyl Reductase Genes—A Report From the Children's Oncology Group

Blanco¹,

Sun²,

Landier³

et al. 2012

JCO

323

262

View full text Add to dashboard Cite

A B S T R A C T PurposeCarbonyl reductases (CBRs) catalyze reduction of anthracyclines to cardiotoxic alcohol metabolites. Polymorphisms in CBR1 and CBR3 influence synthesis of these metabolites. We examined whether single nucleotide polymorphisms in CBR1 (CBR1 1096GϾA) and/or CBR3 (CBR3 V244M) modified the dose-dependent risk of anthracycline-related cardiomyopathy in childhood cancer survivors. Patients and MethodsOne hundred seventy survivors with cardiomyopathy (patient cases) were compared with 317 survivors with no cardiomyopathy (controls; matched on cancer diagnosis, year of diagnosis, length of follow-up, and race/ethnicity) using conditional logistic regression techniques. 2 ) did not increase the risk of cardiomyopathy. Among individuals with CBR3 V244M homozygous G genotypes (CBR3:GG), exposure to low-to moderate-dose anthracyclines increased cardiomyopathy risk when compared with individuals with CBR3:GA/AA genotypes unexposed to anthracyclines (OR, 5.48; P ϭ .003), as well as exposed to low-to moderate-dose anthracyclines (OR, 3.30; P ϭ .006). High-dose anthracyclines (Ͼ 250 mg/m 2 ) were associated with increased cardiomyopathy risk, irrespective of CBR genotype status. Results ConclusionThis study demonstrates increased anthracycline-related cardiomyopathy risk at doses as low as 101 to 150 mg/m 2 . Homozygosis for G allele in CBR3 contributes to increased cardiomyopathy risk associated with low-to moderate-dose anthracyclines, such that there seems to be no safe dose for patients homozygous for the CBR3 V244M G allele. These results suggest a need for targeted intervention for those at increased risk of cardiomyopathy.

show abstract

Cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review

Cited by 49 publications

References 27 publications

The Effect of Dexrazoxane for Clinical and Subclinical Cardiotoxicity in Children With Acute Myeloid Leukemia

The Effect of Dexrazoxane for Clinical and Subclinical Cardiotoxicity in Children With Acute Myeloid Leukemia

Cardiac toxicity associated with anthracycline‐containing chemotherapy in older women with breast cancer

Anthracycline-Related Cardiomyopathy After Childhood Cancer: Role of Polymorphisms in Carbonyl Reductase Genes—A Report From the Children's Oncology Group

Contact Info

Product

Resources

About