***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: Two hundred and thirty five patients with osteosarcoma , aged less than 40 years , and treated by amputation or radiotherapy , were entered in a r and omised trial of two forms of adjuvant chemotherapy . A two drug regimen , namely vincristine 2 mg m-2 ( maximum 2 mg ) followed by methotrexate 200 mgm-2 , given every three weeks , was compared with a three drug regimen , comprising the same vincristine-methotrexate treatment , alternating every three weeks with doxorubicin 60 mg m-2 . Both regimens were continued for 54 weeks . Forty-one patients were excluded , most because of inadequate histology , leaving 194 patients for analysis . One hundred and seventy of these had immediate amputation , 14 were treated by a policy of radiotherapy , with surgery delayed for 9 months , provided no distant metastases had appeared , and 10 by a policy of radiotherapy only . Patients have been followed-up for between 26 and 94 months after entry to the trial . The 2- and 5-year survival rates were 48 % and 27 % . No significant difference in survival was observed between the two regimens , but toxicity was less with the two drug regimen 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 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 Stage III and IV epithelial ovarian cancer patients were prospect ively r and omized to receive eight courses of 60 mg/m2 of cisplatin plus either 75 mg/m2 of epirubicin ( 62 patients ) or 60 mg/m2 of doxorubicin ( 54 patients ) . Clinical response rates for cisplatin/epirubicin of 42 % [ 15 % complete response ( CR ) and 27 % partial response ( PR ) ] and for cisplatin/doxorubicin of 55 % ( 24 % CR and 31 % PR ) were not statistically different ( p = 0.14 ) . The negative second look rate was 35 % ( 10/29 ) for cisplatin/doxorubicin and 17 % ( 5/30 ) for cisplatin/epirubicin ( p = 0.12 ) . The progression-free interval for cisplatin/epirubicin ( 13 months ) was not statistically different ( p = 0.09 ) from that for cisplatin/doxorubicin ( 19 months ) . The median survivals for cisplatin/epirubicin ( 756 days ) and cisplatin/doxorubicin ( 739 days ) were similar ( p = 0.70 ) . Cardiotoxicity was greater for the cisplatin/doxorubicin group ( p = 0.0003 ) . With similar survival and less cardiotoxicity , the cisplatin/epirubicin regimen had the more favorable therapeutic index Fifty-one patients with ovarian cancer were entered in a r and omised trial comparing treatment with cisplatin + adriamycin + cyclophosphamide ( PAC ) to cisplatin + 4'epi-adriamycin + cyclophosphamide ( PEC ) .  Complete response rates for the two treatment arms were similar ( 9/27 PAC , 14/24 PEC ) . Patients with less than 2 cm residual disease had significantly higher rate of complete remission than those with greater than 2 cm residual disease . Cardiotoxicity was significantly less in the PEC-treated group ( 0/24 ) as compared with the PAC-treated group ( 6/27 , chi2 = 4.09 , p less than 0.05 ) A prospect i ve r and omized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin ( 60 mg/m2 every 3 to 4 weeks ) administered by bolus or 72‐hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high‐ grade soft tissue sarcoma of the extremity or superficial trunk .  Cardiac toxicity , defined as a 10 % or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography , was evaluated in 69 patients .  Cardiotoxicity was seen in 61 % of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2 . Among patients who received continuous infusion , 42 % had cardiotoxicity with a median dose of 540 mg/m2 . The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm ( P = 0.0017 ) . Two patients in each group had clinical congestive heart failure , with one cardiac death occurring in each . There was a trend toward a lower rate of metastasis ( P = 0.19 ) and a significantly lower rate of death of disease ( P = 0.036 ) for patients treated with the bolus dose . Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis : blood transfusion within 24 hours of operation ( P < 0.00001 ) , tumor deep to the fascia and 5 cm or more in size ( P = 0.0043 ) , and a histologic subtype other than liposarcoma ( P = 0.0002 ) . The unfavorable effect of continuous infusion was not selected in the model ( P = 0.16 ) . Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational . Furthermore , the impact of perioperative blood transfusion merits further study 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 Amifostine has emerged as a pancytoprotectant shown protection against nephrotoxicity , neurotoxicity and ototoxicity in pre clinical studies . Methods : We design ed a prospect i ve comparative r and omized trial to evaluate the cytoprotective effects of amifostine in patients with osteosarcoma receiving 
    Output:
    
A similar pattern of results were found for sub clinical cardiotoxicity ; with risk significantly greater with anthracycline containing regimens and bolus administration ; and significantly lower risk with epirubicin , liposomal doxorubicin versus doxorubicin but not epirubicin , and with concomitant use of a cardioprotective agent .
Conclusions Evidence is not sufficiently robust to support clear evidence -based recommendations on different anthracycline treatment regimens , or for routine use of cardiac protective agents or liposomal formulations .