***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: The National Surgical Adjuvant Breast and Bowel Project ( NSABP ) implemented protocol B-15 to compare 2 months of Adriamycin ( doxorubicin ; Adria Laboratories , Columbus , OH ) and cyclophosphamide ( AC ) with 6 months of conventional cyclophosphamide , methotrexate , and fluorouracil ( CMF ) in patients with breast cancer nonresponsive to tamoxifen ( TAM , T ) . A second aim was to determine whether AC followed in 6 months by intravenous ( IV ) CMF was more effective than AC without reinduction therapy . Through 3 years of follow-up , findings from 2,194 patients indicate no significant difference in disease-free survival ( DFS , P = .5 ) , distant disease-free survival ( DDFS , P = .5 ) or survival ( S , P = .8 ) among the three groups . Since the outcome from AC and CMF was almost identical , the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients . AC seems preferable since , following total mastectomy , AC was completed on day 63 versus day 154 for conventional CMF ; patients visited health professionals three times as often for conventional CMF as for AC ; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF ; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC . The difference in the amount of alopecia between the two treatment groups was less than anticipated . While alopecia was almost universally observed following AC therapy , 71 % of the CMF patients also had hair loss and , in 41 % , the loss was greater than 50 % . This study and NSABP B-16 , which evaluates the worth of AC therapy in TAM-responsive patients , indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients PURPOSE We evaluated the efficacy of cyclophosphamide , methotrexate , and fluorouracil ( CMF ) versus cyclophosphamide , doxorubicin , and fluorouracil ( CAF ) in node-negative breast cancer patients with and without tamoxifen ( TAM ) , overall and by hormone receptor ( HR ) status . PATIENTS AND METHODS Node-negative patients identified by tumor size ( > 2 cm ) , negative HR , or high S-phase fraction ( n = 2,690 ) were r and omly assigned to CMF , CAF , CMF + TAM ( CMFT ) , or CAF + TAM ( CAFT ) . Cox regression evaluated overall survival ( OS ) and disease-free survival ( DFS ) for CAF versus CMF and TAM versus no TAM separately . Two-sided CIs and one-sided P values for planned comparisons were calculated . RESULTS Ten-year estimates indicated that CAF was not significantly better than CMF ( P = .13 ) for the primary outcome of DFS ( 77 % v 75 % ; HR = 1.09 ; 95 % CI , 0.94 to 1.27 ) . CAF had slightly better OS than CMF ( 85 % v 82 % , HR = 1.19 for CMF v CAF ; 95 % CI , 0.99 to 1.43 ) ; values were statistically significant in the planned one-sided test ( P = .03 ) . Toxicity was greater with CAF and did not increase with TAM . Overall , TAM had no benefit ( DFS , P = .16 ; OS , P = .37 ) , but the TAM effect differed by HR groups . For HR-positive patients , TAM was beneficial ( DFS , HR = 1.32 for no TAM v TAM ; 95 % CI , 1.09 to 1.61 ; P = .003 ; OS , HR = 1.26 ; 95 % CI , 0.99 to 1.61 ; P = .03 ) , but not for HR-negative patients ( DFS , HR = 0.81 for no TAM v TAM ; 95 % CI , 0.64 to 1.03 ; OS , HR = 0.79 ; 95 % CI , 0.60 to 1.05 ) . CONCLUSION CAF did not improve DFS compared with CMF ; there was a slight effect on OS . Given greater toxicity , we can not conclude CAF to be superior to CMF . TAM is effective in HR-positive disease , but not in HR-negative disease PURPOSE To determine whether the combination of pegylated liposomal doxorubicin ( PLD ) and docetaxel significantly prolongs time to disease progression compared with docetaxel alone without an increase in cardiac toxicity in women with advanced breast cancer who had experienced relapse at least 1 year after prior adjuvant or neoadjuvant anthracycline therapy . PATIENTS AND METHODS This international , phase III study r and omly assigned 751 patients to receive either docetaxel 75 mg/m(2 ) ( n = 373 ) or PLD 30 mg/m(2 ) followed by docetaxel 60 mg/m(2 ) every 21 days ( n = 378 ) and continued until disease progression or prohibitive toxicity . The primary end point was time to progression ( TTP ) . Secondary end points were overall survival ( OS ) , objective response rate ( ORR ) , cardiac toxicity , and safety . RESULTS Treatment with PLD-docetaxel significantly improved median TTP from 7.0 to 9.8 months ( hazard ratio [ HR ] = 0.65 ; 95 % CI , 0.55 to 0.77 ; P = .000001 ) and the ORR from 26 % to 35 % ( P = .0085 ) . OS was similar between the two groups ( HR = 1.02 ; 95 % CI , 0.86 to 1.22 ) . The incidence of grade 3 or 4 adverse events were similar ( 78 % v 72 % ) , although a higher incidence of h and -foot syndrome ( 24 % v 0 % ) and mucositis/stomatitis ( 12 % v 1 % ) were observed in the PLD-docetaxel combination . Protocol -defined left ventricular ejection fraction decreases and congestive heart failure were reported in 5 % and 1 % in both treatment arms , respectively . CONCLUSION The PLD-docetaxel combination was more effective than docetaxel alone in women with metastatic breast cancer who had experienced relapse at least 1 year after prior adjuvant anthracycline therapy without an increase in cardiac toxicity , although mucocutaneous toxicity was more common Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Background To evaluate activity and tolerability of two anthracycline-containing regimens as first-line treatment for anthracycline-naïve relapsed breast cancer patients . Methods Patients with relapsed breast cancer not previously treated with adjuvant anthracyclines were r and omly assigned to epirubicin/vinorelbine ( arm A : EPI/VNB , EPI 90 mg/m2 on day 1 , VNB 25 mg/m2 on days 1,5 plus G-CSF subcutaneously on days 7 - 12 , with cycles repeated every 21 days ) , or to pegylated liposomal doxorubicin/VNB ( arm B : PLD/VNB , PLD 40 mg/m2 on day 1 , VNB 30 mg/m2 on days 1 , 15 , with cycles repeated every 4 weeks ) . Primary objective was to evaluate the efficacy of the two regimens in terms of response rate , secondarily toxicity , progression free survival and overall survival . Results One hundred and four patients have been enrolled ( arm A 54 , arm B 50 ) : characteristics were well balanced between the 2 arms . Responses were as follows : arm A , 3 ( 5.6 % ) CR , 20 ( 37 % ) PR , ( ORR 42.6 % , 95%CI 29.3%-55.9 % ) ; arm B , 8 ( 16 % ) CR , 18 ( 36 % ) PR , ( ORR 52 % , 95%CI 38.2%-65.8 % ) . Median progression free survival was 10.7 months in arm A ( 95 % CI , 8.7 - 12.6 ) , and 8.8 months in arm B ( 95 % CI , 7.1 - 10.5 ) . Median overall survival was 34.6 months in arm A ( 95%CI , 19.5 - 49.8 ) and 24.8 months in arm B ( 95%CI , 15.7 - 33.9 ) . As toxicity concerns , both treatment regimens were well tolerated ; myelosuppression was the dose-limiting toxicity , with G3 - 4 neutropenia occurring in 18.5 % and 22 % of the patients of arm A and B , respectively . No relevant differences in main toxic effects have been observed between the two arms , except for alopecia , more common in arm A , and cutaneous toxicity , observed only in arm B. No clinical congestive heart failures have been observed , one case of tachyarrhythmia was reported after the last EPI/VNB cycle , and two reversible ≥ 20 % LVEF decreases have been observed in arm A. Conclusions Both anthracycline- containing regimens evaluated in the present study seem to be active and with a satisfactory tolerability in anthracycline-naïve relapsed breast cancer patients The EORTC Breast Cancer Cooperative Group carried out a r and omized trial to compare doxorubicin with epirubicin as second-line chemotherapy in patients with metastatic breast cancer . Two hundred and fifty-nine patients with at least one site of metastatic disease entered this trial , of whom 232 patients were eligible . Treatment consisted of doxorubicin 75 mg m(-2 ) or epirubicin 90 mg m(-2 ) i.v . every 3 weeks . The overall response rates for doxorubicin and epirubicin were 36 % and 28 % respectively ( P = 0.173 ) . The median time to progression was 23 weeks for doxorubicin and 19 weeks for epirubicin ( P = 0.063 ) and the median duration of response was 40 weeks for doxorubicin and 32 weeks for epirubicin ( P = 0.059 ) . The median survival was 47 weeks for doxorubicin and 44 weeks for epirubicin ( P = 0.196 ) . Leucocyte count on retreatment day ( P = 0.011 ) and platelet nadir ( P = 0.031 ) were significantly lower in the doxorubicin-treated group . Also mucositis ( P < 0.001 ) , diarrhoea ( P = 0.005 ) and haemorrhage ( P = 0.048 ) were significantly worse in the doxorubicin arm . Nine patients on doxorubicin and two patients on epirubicin experienced congestive heart failure ( CHF ) . At the dose levels used in this study , no statistical differences in response rate and survival were found between the two treatment arms . Treatment with doxorubicin tended to result in a slightly longer duration of response and time to progression but doxorubicin was more toxic than epirubicin PURPOSE To compare a full-dose epirubicin-cyclophosphamide ( HEC ) regimen with classical cyclophosphamide , methotrexate , and fluorouracil ( CMF ) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen ( EC ) in the adjuvant therapy of node-positive breast cancer . PATIENTS AND METHODS Node-positive breast cancer patients who were aged 70 years or younger were r and omly allocated to one of the following treatments : CMF for six cycles ( oral cyclophosphamide ) ; EC for eight cycles ( epirubicin 60 mg/m(2 ) , cyclophosphamide 500 mg/m(2 ) ; day 1 every 3 weeks ) ; and HEC for eight cycles ( epirubicin 100 mg/m(2 ) , cyclophosphamide 830 mg/m(2 ) ; day 1 every 3 weeks ) . RESULTS Two hundred fifty-five , 267 , and 25 
    Output:
    
INTERPRETATION DOX has higher CE3 rates than NON does .
LD statistically trended to lower cardiac event rates than DOX .
Non-statistical significance among EPI , LD and DOX with regard to cardiac toxicity indicates that avoidance of CE3 should not motivate selection of a particular anthracycline in otherwise healthy women in whom total lifetime anthracycline exposure will likely be limited .
Overall low incidence of CE3 with any type of anthracycline indicates that we can safely use any anthracycline if cumulative dose limits are not exceeded .
While CE3 does not limit our choice of anthracycline LD appears to be the least cardiotoxic .