***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: Background — An increase in troponin I soon after high-dose chemotherapy ( HDC ) is a strong predictor of poor cardiological outcome in cancer patients . This finding has important clinical implication s and provides a rationale for the development of prophylactic strategies for preventing cardiotoxicity . Angiotensin-converting enzyme inhibitors slow the progression of left ventricular dysfunction in different clinical setting s , but their role in the prevention of cardiotoxicity has never been investigated . Methods and Results — Of the 473 cancer patients evaluated , 114 ( 72 women ; mean age , 45±12 years ) who showed a troponin I increase soon after HDC were r and omized to receive ( angiotensin-converting enzyme inhibitor group ; 20 mg/d ; n=56 ) or not to receive ( control subjects ; n=58 ) enalapril . Treatment was started 1 month after HDC and continued for 1 year . Cardiological evaluation was performed at baseline and at 1 , 3 , 6 , and 12 months after HDC . The primary end point was an absolute decrease > 10 percent units in left ventricular ejection fraction , with a decline below the normal limit value . A significant reduction in left ventricular ejection fraction and an increase in end-diastolic and end-systolic volumes were observed only in untreated patients . According to the Kaplan-Meier analysis , the incidence of the primary end point was significantly higher in control subjects than in the angiotensin-converting enzyme inhibitor group ( 43 % versus 0 % ; P<0.001 ) . Conclusions — In high-risk , HDC-treated patients , defined by an increased troponin I value , early treatment with enalapril seems to prevent the development of late cardiotoxicity Anthracyclines are the most frequent cause of iatrogenic congestive heart failure ranging from acute reversible minor , irreversible reduction in the left ventricular ejection fraction and death despite preventive measures . Sensitive methods are needed to detect earliest pre clinical cardiotoxicity along with the development of new protective agents . Thirty breast cancer patients were r and omly treated with q 21 120 mg/m2 Epirubicin ( EPI ) x 3 , alone ( 10 patients ) , or + ICRF-187 ( 1000 mg/m2 ) ( 10 patients ) or + C0Q10 ( 50 mg/day ) ( 10 patients ) and monitored by Thoracic Electrical Bioimpedance ( TEB ) cardiography before ( T0 ) and at the end of chemotherapy ( T1 ) , then at 1 , 3 , 6 months of follow up ( F1 , F2 , F3 ) . a ) The group treated with EPI alone showed , between F1-F2 , a significant ( p < 0.05 ) decrease in Stroke Index ( S1 ) . Acceleration Index ( ACI ) and a significant ( p < 0.05 ) increase in Systemic Vascular Resistance Index ( SVRI ) , while between F2 and F3 it showed a significant ( p < 0.05 ) recovery in S1 and ACI . b ) The group treated with EPI + ICRF-187 showed , between F1 and F2 a significant decrease in S1 and ACI ( p < 0.05 , p < 0.01 respectively ) and a significant ( p < 0.05 ) increase in SVRI : between F2-F3 ACI had a significant ( p < 0.05 ) recovery : c ) The group treated with EPI + C0Q10 showed no modification in Sl , ACI , and SVRI during the study . The ejection Fraction ( EF ) remained unchanged during the study in all the groups . C0Q10 seems to prevent early decreases in cardiac performance and contractiling , thus avoiding an SVRI increase , while ICRF-187 did not . Since ICRF-187 acts by binding iron , we deem that the earliest cardiac involvement , may occur before iron overload ; therefore the role of ICRF-187 and C0Q10 in acute or chronic heart toxicity was correlated with high-dose anthracycline and needs to be further investigated BACKGROUND The current treatment of hematologic malignancies includes diverse potentially cardiotoxic chemotherapy agents , including high-dose myeloablative regimens used in autologous hematopoietic stem cell transplantation ( HSCT ) . Many of these treatments could induce left ventricular dysfunction ( LVD ) , and limit their efficacy . Angiotensin-converting enzime inhibitors and beta-blockers prevent LVD and prolong survival after infa rct ion , and recent animal and pilot clinical studies suggest that they can prevent the development of chemotherapy-induced cardiac toxicity . METHODS This is a prevention , parallel-assignment , r and omized , controlled , clinical efficacy study . Ninety patients recently diagnosed of acute leukemia or undergoing autologous HSCT and with normal LV ejection fraction will be r and omized to enalapril and carvedilol or to the control group . Echocardiogram and a cardiac magnetic resonance imaging studies will be performed at baseline and 6 - 9 months after r and omization . The primary efficacy endpoint is the change from baseline in LV ejection fraction . Secondary endpoints include the assessment of LV volumes and diastolic function , and the incidence of death , heart failure , or LVD . CONCLUSIONS The OVERCOME study will be the first clinical trial to test the preventive efficacy on LVD of combined treatment with enalapril and carvedilol administered to patients with hematologic malignancies su bmi tted to current treatment with intensive chemotherapy PURPOSE To test potential protection by ICRF-187 against cumulative doxorubicin-dose-related cardiac toxicity , we conducted a r and omized clinical trial in 150 women with advanced breast cancer . PATIENTS AND METHODS Patients received fluorouracil ( 5FU ) 500 mg/m2 , doxorubicin 50 mg/m2 , and cyclophosphamide 500 mg/m2 every 21 days intravenously ( IV ) ( control regimen , 74 patients ) , or the same regimen preceded by ICRF-187 1,000 mg/m2 IV ( experimental regimen , 76 patients ) . RESULTS We previously reported that ICRF-187 in this dose and schedule provides cardiac protection and does not substantially alter the noncardiac toxicity or antitumor efficacy of the control regimen . In this up date d analysis of the entire patient cohort , we provide additional support for these findings and demonstrate that patients in the ICRF-187 group received more cycles ( median , 11 ) and higher cumulative doses ( median , 500 mg/m2 ) of doxorubicin than patients in the control group ( median , nine cycles , P less than .01 ; and 441 mg/m2 , P less than .05 ) . Twenty-six patients in the ICRF-187 group received doxorubicin doses of at least 700 mg/m2 , and among them , 11 patients received 1,000 mg/m2 or more . Only three patients in the control group received doxorubicin doses of 700 mg/m2 ; the maximum dose administered to one patient in this group was 950 mg/m2 . ICRF-187 cardiac protection was demonstrated by difference in incidence of clinical congestive heart failure ( CHF ; two patients in the ICRF-187 group v 20 in the control group ; P less than .0001 ) and by differences in resting left ventricular ejection fraction ( LVEF ) determined by multigated radionuclide ( MUGA ) scan from baselines and that required patient removal from study ( five patients in the ICRF-187 group had a decrease in LVEF to less than 0.45 or a decrease from the baseline LVEF of 0.20 or more v 32 in the control group ; P less than .000001 ) . Among the 30 patients who had an assessable endomyocardial biopsy at cumulative doxorubicin 450 mg/m2 , none of 16 in the ICRF-187 group and six of 14 in the control group had a score of 2 ( P less than .05 ) . ICRF-187 cardiac protection was observed in patients with and without prior chest-wall radiation or other risk factors for developing doxorubicin cardiac toxicity . CONCLUSION By protecting against cumulative doxorubicin-induced cardiac toxicity , ICRF-187 permits significantly greater doses of doxorubicin to be administered to patients with greater safety PURPOSE To determine the cardioprotective effect of dexrazoxane ( DZR ) used in a doxorubicin-based combination therapy in advanced breast cancer . PATIENTS AND METHODS Between November 1988 and January 1991 , 534 patients with advanced breast cancer were r and omized to two multicenter , double-blind studies ( 088001 and 088006 ) . Patients received fluorouracil , doxorubicin , and cyclophosphamide ( FAC ) with either DZR ( DZR-to-doxorubicin ratio , 10:1 ) or placebo ( PLA ) every 3 weeks and were monitored with serial multiplegated acquisition ( MUGA ) scans . RESULTS The hazards ratio ( HR ) of PLA to DZR for a cardiac event , which was predefined ejection fraction changes or congestive heart failure ( CHF ) , was 2.63 ( 95 % confidence interval [ CI ] , 1.61 to 4.27 ; P < .001 ) for 088001 and 2.00 ( 95 % CI , 1.01 to 3.96 ; P = .038 ) for 088006 . The objective response rates for 088001 were 46.8 % for DZR and 60.5 % for PLA , a difference of 14 % ( 95 % CI , -25 % to -2 % ; P = .019 ) , and for 088006 were 53.7 % for DZR and 49.3 % for PLA , a difference of 4 % ( 95 % CI , -13 % to 22 % ; P = .63 ) . Time to progression and survival were not significantly different between treatment arms in either study . Toxicities on the DZR arms included lower granulocyte and platelet counts at nadir ( P = .009 and P = .004 , respectively ) and more pain on injection ( P = .001 ) , with no difference in the rates of fever , infection , or hemorrhage . CONCLUSION DZR had a significant cardioprotective effect as measured by noninvasive testing and clinical CHF . One of the two studies ( 088001 ) showed a lower response rate with DZR , but time to progression and survival were not significantly different . DZR is the first agent shown to reduce cardiotoxicity from doxorubicin Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more PURPOSE Dexrazoxane was found effective in reducing  doxorubicin cardiotoxicity when given at a dose ratio ( dexrazoxane : doxorubicin ) of 20:1 . Pre clinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity . The main objective of this study was to investigate the efficacy of dexrazoxane , given at a dose ratio of 10:1 against epirubicin cardiotoxicity . PATIENTS AND METHODS One hundred sixty-two advanced breast cancer patients were r and omized to receive epirubicin-based chemotherapy with or without dexrazoxane .  Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously ( IV ) , epirubicin 60 mg/m2 IV , and fluorouracil 600 mg/m2 IV , on day 1 every 3 weeks . The other patients were treated with epirubicin 120 mg/m2 IV on day 1 every 3 weeks . Cardiac toxicity was defined as clinical signs of congestive heart failure , a decrease in resting left ventricular ejection fraction ( LVEF ) to < or = 45 % , or a decrease from baseline resting LVEF of > or = 20 EF units . RESULTS One hundred sixty patients were evaluated .  Cardiotoxicity was recorded in 18 of 78 patients ( 23.1 % ) in the control arm and in six of 82 ( 7.3 % ) in the dexrazoxone arm . The cumulative probability of developing cardiotoxicity was significantly lower in  dexrazoxane-treated  patients than in control patients ( P = .006 ; odds ratio , 0.29 ; 95 % confidence limit [ CL ] , 0.09 to 0.78 ) . Noncardiac toxicity , objective response , progression-free survival , and overall survival were similar in both arms . CONCLUSION Dexrazoxane given at a dexrazoxane : epirubicin dose ratio of 10:1 protects against epirubicin-induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubic 
    Output:
    
Available data suggested that dexrazoxane and angiotensin antagonists did not affect malignancy response rate or risk of death .
Conclusion Moderate quality data suggest that dexrazoxane , and low quality data suggest angiotensin antagonists , are likely to be effective for cardiotoxicity prevention