***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 Bosutinib is an oral Src/Abl tyrosine kinase inhibitor . The phase III Bosutinib Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia ( BELA ) trial compared bosutinib with imatinib in newly diagnosed , chronic-phase chronic myeloid leukemia ( CML ) . PATIENTS AND METHODS A total of 502 patients were r and omly assigned 1:1 to bosutinib 500 mg per day or imatinib 400 mg per day . RESULTS The complete cytogenetic response ( CCyR ) rate at 12 months was not different for bosutinib ( 70 % ; 95 % CI , 64 % to 76 % ) versus imatinib ( 68 % ; 95 % CI , 62 % to 74 % ; two-sided P = .601 ) ; therefore , the study did not achieve its primary end point . The major molecular response ( MMR ) rate at 12 months was higher with bosutinib ( 41 % ; 95 % CI , 35 % to 47 % ) compared with imatinib ( 27 % ; 95 % CI , 22 % to 33 % ; two-sided P < .001 ) . Time to CCyR and MMR was faster with bosutinib compared with imatinib ( two-sided P < .001 for both ) . On-treatment transformation to accelerated/blast phase occurred in four patients ( 2 % ) on bosutinib compared with 10 patients ( 4 % ) on imatinib . A total of three CML-related deaths occurred on the bosutinib arm compared with eight on the imatinib arm . The safety profiles of bosutinib and imatinib were distinct ; GI and liver-related events were more frequent with bosutinib , whereas neutropenia , musculoskeletal disorders , and edema were more frequent with imatinib . CONCLUSION This ongoing trial did not meet its primary end point of CCyR at 12 months , despite the observed higher MMR rate at 12 months , faster times to CCyR and MMR , fewer on-treatment transformations to accelerated/blast phase , and fewer CML-related deaths with bosutinib compared with imatinib . Each drug had a distinct safety profile BACKGROUND Imatinib slows development of chronic myeloid leukemia ( CML ) . However , available information on morbidity and mortality is largely based on sponsored trials , whereas independent long-term field studies are lacking . PATIENTS AND METHODS Consecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission ( CCyR ) after 2 years ( ± 3 months ) were eligible for enrollment in the independent multicenter Imatinib Long-Term ( Side ) Effects ( ILTE ) study . Incidence of the first serious and nonserious adverse events and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the st and ard log-rank test . Attainment of negative Philadelphia chromosome hematopoiesis was assessed with cytogenetics and quantitative polymerase chain reaction . Cumulative incidence of death related or unrelated to CML progression was estimated , accounting for competing risks , according to the Kalbleisch-Prentice method . St and ardized incidence ratios were calculated based on population rates specific for sex and age classes . Confidence intervals were calculated by the exact method based on the χ(2 ) distribution . All statistical tests were two-sided . RESULTS A total of 832 patients who were treated for a median of 5.8 years were enrolled . There were 139 recorded serious adverse events , of which 19.4 % were imatinib-related . A total of 830 nonserious adverse events were observed in 53 % of patients ; 560 ( 68 % ) were imatinib-related . The most frequent were muscle cramps , asthenia , edema , skin fragility , diarrhea , tendon , or ligament lesions . Nineteen patients ( 2.3 % ) discontinued imatinib because of drug-related toxic effects . Forty-five patients lost CCyR , at a rate of 1.4 per 100 person-years . Durable ( > 1 year ) negative Philadelphia chromosome hematopoiesis was attained by 179 patients . Twenty deaths were observed , with a 4.8 % mortality incidence rate ( st and ardized incidence ratio = 0.7 ; 95 % confidence interval = 0.40 to 1.10 , P = .08 ) , with only six ( 30 % ) associated with CML progression . CONCLUSIONS In this study , CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib , and survival was not statistically significantly different from that of the general population BACKGROUND Imatinib , a selective inhibitor of the BCR-ABL tyrosine kinase , produces high response rates in patients with chronic-phase chronic myeloid leukemia ( CML ) who have had no response to interferon alfa . We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML . METHODS We r and omly assigned 1106 patients to receive imatinib ( 553 patients ) or interferon alfa plus low-dose cytarabine ( 553 patients ) . Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met . Patients were evaluated for hematologic and cytogenetic responses , toxic effects , and rates of progression . RESULTS After a median follow-up of 19 months , the estimated rate of a major cytogenetic response ( 0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome ) at 18 months was 87.1 percent ( 95 percent confidence interval , 84.1 to 90.0 ) in the imatinib group and 34.7 percent ( 95 percent confidence interval , 29.3 to 40.0 ) in the group given interferon alfa plus cytarabine ( P<0.001 ) . The estimated rates of complete cytogenetic response were 76.2 percent ( 95 percent confidence interval , 72.5 to 79.9 ) and 14.5 percent ( 95 percent confidence interval , 10.5 to 18.5 ) , respectively ( P<0.001 ) . At 18 months , the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group ( P<0.001 ) . Imatinib was better tolerated than combination therapy . CONCLUSIONS In terms of hematologic and cytogenetic responses , tolerability , and the likelihood of progression to accelerated-phase or blast-crisis CML , imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML Underst and ing the impact of second-line tyrosine kinase inhibitor therapy on the health-related quality of life ( HRQOL ) of  imatinib (IM)-resistant and IM-intolerant chronic phase chronic myeloid leukemia ( CP CML ) patients is important given the increased survival that comes with therapy . As part of a bosutinib single-arm phase 2 trial , 200 IM-resistant and 88 IM-intolerant CP CML patients '  HRQOL was assessed prior to and throughout treatment with the Functional Assessment of Cancer Therapy-Leukemia ( FACT-Leu ) . Little HRQOL impairment was demonstrated at baseline . Over the course of 96 weeks on bosutinib therapy , patients noted statistically significant and /or clinical ly meaningful improvements on several FACT-Leu scales Imatinib ( Gleevec ) , a highly effective specific tyrosine kinase inhibitor , demonstrates a better side effect profile than interferon-alpha ( IFN ) , which impairs patients ' quality of life ( QoL ) . This phase III international study evaluated QoL outcomes in 1,106 newly diagnosed patients with chronic-phase chronic myeloid leukemia ( CML ) who were r and omized to receive either imatinib 400 mg daily or IFN up to 5 MU/m(2)/d with cytarabine ( Ara-C ) 20 mg/m(2)/d added for 10 days every month ( IFN + LDAC ) . Crossover to the other treatment arm was permitted due to a lack of efficacy or treatment intolerance . QoL was assessed with the Functional Assessment of Cancer Therapy-Biologic Response Modifiers ( FACT-BRM ) at baseline , monthly for 6 months and then at months 9 , 12 , and 18 . The Trial Outcome Index ( TOI ; a composite endpoint of physical/functional/treatment-specific subscales ) was the primary endpoint . Secondary endpoints measured were social/family well-being ( SFWB ) and emotional well-being ( EWB ) . QoL was analyzed for the first 18 months of treatment using mixed effects growth curve models . The primary analyses were intention-to-treat ( ITT ) ; secondary analyses incorporated crossover as a time-dependent covariate . A total of 1,049 patients completed at least one QoL assessment . Two hundred sixty-one patients ( 50 % ) crossed over from IFN to imatinib and 11 ( 2 % ) crossed over from imatinib to IFN . There was a significant decline in TOI scores for the IFN treatment arm compared with preservation of baseline TOI scores in the imatinib arm ( P < .001 , ITT ) . Mean social/family and EWB scores were 22.8 and 19.5 , respectively , for imatinib and 21.6 and 17.6 , respectively , for IFN ( P < .001 , ITT ) . After crossing over from IFN to imatinib , patients experienced a significant ( P < .001 ) increase in TOI scores .  Imatinib offers clear QoL advantages over IFN as first-line treatment of chronic-phase CML . In addition , patients who crossed over to imatinib reported higher QoL than those who remained on IFN . Semin Hematol 40(suppl 2):31 - 36 PURPOSE Quality of life ( QOL ) outcomes in patients with chronic myeloid leukemia ( CML ) were evaluated in an international phase III study . PATIENTS AND METHODS Newly diagnosed patients with chronic phase CML were r and omly assigned to imatinib or interferon alfa plus subcutaneous low-dose cytarabine ( IFN+LDAC ) . Cross-over to the other treatment was permitted because of intolerance or lack of efficacy . Patients completed cancer-specific QOL ( Functional Assessment of Cancer Therapy-Biologic Response Modifiers ) and utility ( Euro QoL-5D ) question naires at baseline and during treatment ( n = 1,049 ) . The primary QOL end point was the Trial Outcome Index ( TOI ; a measure of physical function and well-being ) . Secondary end points included social and family well-being ( SFWB ) , emotional well-being ( EWB ) , and the utility score . Primary analyses were intention to treat with secondary analyses accounting for cross-over . RESULTS Patients receiving IFN+LDAC experienced a large decline in the TOI , whereas those receiving imatinib maintained their baseline level . Treatment differences at each visit were significant ( P < .001 ) and clinical ly relevant in favor of imatinib .  Mean SFWB , EWB , and utility scores were also significantly better for those patients taking imatinib . Patients who crossed over to imatinib experienced a large increase in TOI ; significant ( P < .001 ) differences were observed between patients who did and did not cross over in favor of imatinib . CONCLUSION Imatinib offers clear QOL advantages compared with IFN+LDAC as first-line treatment of chronic phase CML . In addition , patients who cross over to imatinib from IFN+LDAC experience a significant improvement in QOL compared with patients who continue to take IFN+LDAC Imatinib mesylate ( IM ) is a first-line treatment of chronic phase-chronic myeloid leukemia ( CP-CML ) . The primary objective of this study was to assess the quality of life ( QOL ) in patients with CP-CML treated with IM . Ninety patients with newly diagnosed CP-CML were assessed for QOL with first-line IM . Patients completed the cancer-specific FACT-BRM question naire ( functional assessment of cancer therapy-biologic response modifiers ) at baseline and at 3 and 6 months . FACT-BRM consists of subscales including physical well-being ( PWB ) , social and family well-being ( SFWB ) , emotional well-being ( EWB ) , functional well-being ( FWB ) , BRM-physical , and BRM-mental . The primary endpoint was the Trial Outcome Index ( TOI ) , created as a measure of physical function and well-being . An increase of ≥5 from baseline was considered to be a clinical ly significant improvement . The mean TOI score increased from 75.5 at baseline to 85.2 ( p<0.0001 ) at 6 months , representing a healthy QOL . When comparing the individual TOI subscales , there was a mean increase of 16.4 in the daily functioning and well-being score , and a mean decrease of 6.2 , 4.9 , and 16.1 was noted in fatigue , emotional/cognitive dysfunction , and side-effects scores at 6 months , respectively . Improvement was not affected by age , sex , or Sokal score . With prolonged treatment , IM results in a higher physical well- 
    Output:
    
The most solid data in this area indicate that CML patients receiving TKIs  have a worse HRQOL profile when compared to their peers , without cancer , in the general population and interventions to improve HRQOL outcomes are thus needed .
However , HRQOL assessment in these studies emphasize the unique information provided by the patient 's perspective .