***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE We conducted an open-label , r and omized trial to determine whether ICRF-187 would reduce doxorubicin-induced cardiotoxicity in pediatric sarcoma patients . METHODS Thirty-eight patients were r and omized to receive doxorubicin-containing chemotherapy ( given as an intravenous bolus ) with or without ICRF-187 .  Resting left ventricular ejection fraction ( LVEF ) was monitored serially with multigated radionuclide angiography ( MUGA ) scan . The two groups were compared for incidence and degree of cardiotoxicity , response rates to four cycles of chemotherapy , event-free and overall survival , and incidence and severity of noncardiac toxicities . RESULTS Eighteen ICRF-187-treated and 15 control patients were assessable for cardiac toxicity .  ICRF-187-treated patients were less likely to develop sub clinical cardiotoxicity ( 22 % v 67 % , P < .01 ) , had a smaller decline in LVEF per 100 mg/m2 of doxorubicin ( 1.0 v 2.7 percentage points , P = .02 ) , and received a higher median cumulative dose of doxorubicin ( 410 v 310 mg/m2 , P < .05 ) than did control patients . Objective response rates were identical in the two groups , with no significant differences seen in event-free or overall survival .  ICRF-187-treated patients had a significantly higher incidence of transient grade 1 serum transaminase elevations and a trend toward increased hematologic toxicity . CONCLUSION ICRF-187 reduces the risk of developing short-term sub clinical cardiotoxicity in pediatric sarcoma patients who receive up to 410 mg/m2 of doxorubicin . Response rates to chemotherapy , event-free and overall survival , and noncardiac toxicities appear to be unaffected by the use of ICRF-187 . Additional clinical trials with larger numbers of patients are needed to determine if the short-term cardioprotection afforded by ICRF-187 will reduce the incidence of late cardiac complications in long-term survivors of childhood cancer Anthracyclines are a group of drugs that are useful in the treatment of Hodgkin 's disease , but have been associated with severe , and in some cases lethal , cardiac toxicity . Apparently , cardiac toxicity is more frequent after 10 years of anthracycline therapy , but no longer studies of cardiac toxicity have been reported . Four hundred and seventy-six patients with Hodgkin 's disease , stages III and IV , were r and omly assigned to receive ABVD ( doxorubicin , bleomycin , vinblastine and dacarbazine ) compared with EBVD ( epirubicin instead of doxorubicin ) and MBVD ( mitoxantrone instead of doxorubicin ) at st and ard doses . The endpoint was the presence of a clinical cardiac event ( CCE ) or abnormalities in equilibrium radionuclide angiocardiography ( ERNA ) and echocardiogram . The patients did not receive radiation therapy and when relapsed they were censored from cardiac toxicity . The median follow-up was 11.5 years ( range 7.5 - 14.8 years ) . CCE was observed in 17 % in the MBVD arm , 9 % in the ABVD arm and 6 % in the EBVD arm ( P < 0.001 ) . Mortality associated with CCE was 12 % with MBVD , 7 % with ABVD and 2 % with EBVD . Abnormalities in ERNA and echocardiogram were observed 6 - 36 months before the presence of a CCE . An excess in the st and ard mortality ratio was observed with the 3 regimens when compared with the general population : 19.4 for EBVD , 46.0 for ABVD and 67.8 for MBVD , which was confirmed with an increase in absolute excess risk/10,000 person-years of 15.6 , 39.0 and 58.7 , respectively . Overall survival was better in patients treated with EBVD because less cardiac events were observed . The use of mitoxantrone was associated with a high rate of relapse and cardiac events . Thus , we would not recommend use of the drug in Hodgkin 's disease . ERNA and echocardiogram are early detection tests for cardiac toxicity and can be employed in surveillance studies BACKGROUND Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia ( ALL ) but also injures myocardial cells . Dexrazoxane , a free-radical scavenger , may protect the heart from doxorubicin-associated damage . METHODS To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes , we r and omly assigned 101 children with ALL to receive doxorubicin alone  ( 30 mg per square meter of body-surface area every three weeks for 10 doses ) and 105 to receive dexrazoxane ( 300 mg per square meter ) followed immediately by doxorubicin . Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin . A total of 2377 serum sample s ( mean , 15.1 sample s per patient ) were obtained before , during , and after treatment with doxorubicin .  Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated ( > 0.01 ng per milliliter)--the primary end point -- or extremely elevated ( > 0.025 ng per milliliter ) . RESULTS Elevations of troponin T occurred in 35 percent of the patients ( 55 of 158 ) . Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels ( 50 percent vs. 21 percent , P<0.001 ) and extremely elevated troponin T levels ( 32 percent vs. 10 percent , P<0.001 ) . The median follow-up was 2.7 years . The rate of event-free survival at 2.5 years was 83 percent in both groups ( P=0.87 by the log-rank test ) . CONCLUSIONS Dexrazoxane prevents or reduces cardiac injury , as reflected by elevations in troponin T , that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin . Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival Doxorubicin has been used in the the treatment of malignant tumors in children . Its use is limited by cardiotoxic effects beyond a cumulative dose of 450 mg/m2 . To detect cardiotoxicity at an early stage and identify patients at risk for development of cardiotoxicity are matters of concern . Recently , cardiac troponin I ( cTnI ) has been reported to be useful for detecting minor myocardial damage . In the present study , we investigated whether cumulative doxorubicin-related myocardial cell damage can potentially increase cTnI levels above the expected values in 22 patients treated with cumulative doxorubicin doses of 120 to 450 mg/m2 .  Impaired cardiac functions were found in three patients by echocardiography , but serum CTnI levels were within the ranges expected in healthy individuals both in patients with cumulative doxorubicin doses > or = 400 mg/m2 and in patients with disturbed cardiac functions . We found no relationship between serum cTnI , cumulative dose of doxorubicin , and echocardiographical findings Two hundred fourteen eligible patients with previously untreated , localized Ewing 's sarcoma of bone were r and omized on IESS-II to receive Adriamycin ( ADR ; doxorubicin ; Adria Laboratories , Columbus , OH ) , cyclophosphamide , vincristine , and dactinomycin by either a high-dose intermittent method ( treatment [ trt ] 1 ) or a moderate-dose continuous method ( trt 2 ) similar to the four-drug arm of IESS-I. Patient characteristics ( sex , primary site , type of surgery ) were stratified at the time of registration ; these and other patient characteristics ( age , time from symptoms to diagnosis , race ) were distributed similarly between treatments . Surgical resection was encouraged , but not m and atory . Local radiation therapy was the same as for IESS-I. The median follow-up time is 5.6 years . The overall outcome was significantly better on trt 1 than on trt 2 . At 5 years , the estimated percentages of patients who were disease-free , relapse-free , and surviving were 68 % , 73 % , and 77 % for trt 1 and 48 % , 56 % , and 63 % for trt 2 ( P = .02 , .03 , and .05 , respectively ) . The major reason for treatment failure for both treatment groups was the development of metastatic disease . The lung was the most common site of metastases followed by bone sites . The combined incidence of severe or worse toxicity ( 67 % ) was comparable between the treatments ; however , severe or worse cardiovascular toxicity was significantly greater on trt 1 . Tne only treatment-associated deaths ( N = 3 ) were on trt 1 and were cardiac-related The objective of this study is to assess the efficacy of ICRF-187 as a protective agent against anthracycline cardiotoxicity . Cardiac function was evaluated by echocardiography before and after each cycle of anthracycline chemotherapy associated with ICRF-187 and compared with that of a second group receiving anthracycline chemotherapy without ICRF-187 . The patients were a group of 15 consecutive children affected with various types of solid tumors who were treated with either doxorubicin-daunomycin or epirubicin ( average doses 340 and 280 mg/m2 , respectively ) , and treatment was associated with ICRF-187 . A second group of 15 consecutive children affected with different malignancies were simultaneously treated with either doxorubicin-daunomycin or epirubicin ( average doses 309 and 270 mg/m2 , respectively ) , but without ICRF-187 association . None of the patients treated with anthracyclines and ICRF-187 association showed abnormalities on echocardiographic examination . In the second group of patients treated with anthracyclines but without ICRF-187 association , we observed a decrease in the left ventricular ejection fraction to < 55 % and a decrease in the left ventricular fractional shortening to < 28 % in two patients ( 13.3 % ) . One of these ( 6.6 % ) showed a dilatative cardiomyopathy . Both groups of patients were treated with low doses of anthracyclines . Although this study was not r and omized , in patients without ICRF-87 cardioprotection , there was a trend for a worse evolution with one case of clinical cardiomyopathy as well as sub clinical cardiac abnormalities Doxorubicin is one of the most effective anticancer drug , but its usefulness is limited by the risk of developing cardiomyopathy , cardiac dysfunction and ventricular arrhythmias .  Dexrazoxane is used to protect against  doxorubicin cardiotoxicity . It is uncertain whether the dexrazoxane-mediated cardioprotective effect will be reflected in electrophysiological properties of the heart . The aim of the present study was to evaluate the occurrence of frequency-domain signal-averaged electrocardiographic ( SAECG ) abnormalities of the QRS complex and the initial ST segment in patients treated with and without dexrazoxane . Thirty children and young adults 2 months - 15 years after completion of doxorubicin-containing therapy for Hodgkin 's disease were evaluated with SAECG .  Patients from group I ( n = 13 ) received combined therapy with doxorubicin and dexrazoxane ( DOX/DZX ) , patients from group II ( n = 17 ) received doxorubicin without dexrazoxane ( DOX ) . Using fast Fourier transformation within the QRS complex and the initial ST segment , area ratio ( AR ) values 40 - 100/0 - 40 Hz were calculated . Significant differences in these frequency parameters in the QRS complex between DOX/DZX group and DOX group ( 19.45+/-12.72 vs 46.18+/-43.06 ; p = 0.03 ) might indicate protective effect of dexrazoxane on electrophysiological myocardial properties Doxorubicin is an anthracycline antibiotic with a broad spectrum of antineoplastic activity . Cardiotoxicity is a serious long-term complication of the drug . Simultaneous administration of carnitine has been proposed to prevent cardiotoxicity . We aim ed to monitor the serum carnitine levels during the treatment of doxorubicin and to determine a relationship between serum carnitine levels and cardiac dysfunction . Fifteen patients were evaluated prospect ively . Measurement of carnitine levels and evaluation of cardiac function were performed prior to treatment , and after cumulative doses of 180 and 300 mg/m2 of doxorubicin .  A group of 20 healthy children served as control group to obtain reference values . We found sub clinical abnormalities in cardiac function , while the cum 
    Output:
    
Two cohort studies considering atrial natriuretic peptide and two considering brain ( B-type ) natriuretic peptide suggested that these chemicals are elevated in some subgroups of children treated with anthracyclines for cancer .
This will have an impact on cardiac services and costs .