***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 efficacy of bendamustine versus chlorambucil in a phase III trial of previously untreated patients with Binet stage B/C chronic lymphocytic leukaemia ( CLL ) was re‐evaluated after a median observation time of 54 months in May 2010 . Overall survival ( OS ) was analysed for the first time . At follow‐up , investigator‐assessed complete response ( CR ) rate ( 21·0 % vs 10·8 % ) , median progression‐free survival ( 21·2 vs 8·8 months ; P < 0·0001 ; hazard ratio 2·83 ) and time to next treatment ( 31·7 vs 10·1 months ; P < 0·0001 ) were improved for bendamustine over chlorambucil  . OS was not different between groups for all patients or those ≤65 years , > 65 years , responders and non‐responders . However , patients with objective response or a CR experienced a significantly longer OS than non‐responders or those without a CR . Significantly more patients on chlorambucil progressed to second/further lines of treatment compared with those on bendamustine ( 78·3 % vs 63·6 % ; P = 0·004 ) . The benefits of bendamustine over chlorambucil were achieved without reducing quality of life . In conclusion , bendamustine is significantly more effective than chlorambucil in previously untreated CLL patients , with the achievement of a CR or objective response appearing to prolong OS . Bendamustine should be considered as a preferred first‐line option over chlorambucil for CLL patients ineligible for fludarabine , cyclophosphamide and rituximab Although chronic lymphocytic leukemia ( CLL ) is a disease of elderly patients , subjects older than 65 years are heavily underrepresented in clinical trials . The German CLL study group ( GCLLSG ) initiated a multicenter phase III trial for CLL patients older than 65 years comparing first-line therapy with fludarabine with chlorambucil .  A total of 193 patients with a median age of 70 years were r and omized to receive fludarabine ( 25 mg/m(2 ) for 5 days intravenously , every 28 days , for 6 courses ) or chlorambucil ( 0.4 mg/kg body weight [ BW ] with an increase to 0.8 mg/kg , every 15 days , for 12 months ) . Fludarabine result ed in a significantly higher overall and complete remission rate ( 72 % vs 51 % , P = .003 ; 7 % vs 0 % , P = .011 ) . Time to treatment failure was significantly shorter in the chlorambucil arm ( 11 vs 18 months ; P = .004 ) , but no difference in progression-free survival time was observed ( 19 months with fludarabine , 18 months with chlorambucil ; P = .7 ) . Moreover , fludarabine did not increase the overall survival time ( 46 months in the fludarabine vs 64 months in the chlorambucil arm ; P = .15 ) . Taken together , the results suggest that in elderly CLL patients the first-line therapy with fludarabine alone does not result in a major clinical benefit compared with chlorambucil . This trial is registered with www.is rct n.org under identifier IS RCT N 36294212 BACKGROUND Previous studies of patients with chronic lymphocytic leukaemia reported high response rates to fludarabine combined with cyclophosphamide . We aim ed to establish whether this treatment combination provided greater survival benefit than did chlorambucil or fludarabine . METHODS 777 patients with chronic lymphocytic leukaemia requiring treatment were r and omly assigned to fludarabine ( n=194 ) or fludarabine plus cyclophosphamide ( 196 ) for six courses , or chlorambucil ( 387 ) for 12 courses . The primary endpoint was overall survival , with secondary endpoints of response rates , progression-free survival , toxic effects , and quality of life . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number NCT 58585610 . FINDINGS There was no significant difference in overall survival between patients given fludarabine plus cyclophosphamide , fludarabine , or chlorambucil .  Complete and overall response rates were better with fludarabine plus cyclophosphamide than with fludarabine ( complete response rate 38%vs 15 % , respectively ; overall response rate 94%vs 80 % , respectively ; p<0.0001 for both comparisons ) , which were in turn better than with chlorambucil ( complete response rate 7 % , overall response rate 72 % ; p=0.006 and 0.04 , respectively ) . Progression-free survival at 5 years was significantly better with fludarabine plus cyclophosphamide ( 36 % ) than with fludarabine ( 10 % ) or chlorambucil ( 10 % ; p<0.00005 ) . Fludarabine plus cyclophosphamide was the best combination for all ages , including patients older than 70 years , and in prognostic groups defined by immunoglobulin heavy chain gene ( V(H ) ) mutation status and cytogenetics , which were tested in 533 and 579 cases , respectively . Patients had more neutropenia and days in hospital with fludarabine plus cyclophosphamide , or fludarabine , than with chlorambucil . There was less haemolytic anaemia with fludarabine plus cyclophosphamide ( 5 % ) than with fludarabine ( 11 % ) or chlorambucil ( 12 % ) . Quality of life was better for responders , but preliminary analyses showed no significant difference between treatments . A meta- analysis of these data and those of two published phase III trials showed a consistent benefit for the fludarabine plus cyclophosphamide regimen in terms of progression-free survival . INTERPRETATION Fludarabine plus cyclophosphamide should now become the st and ard treatment for chronic lymphocytic leukaemia and the basis for new protocol s that incorporate monoclonal antibodies BACKGROUND Chronic lymphocytic leukemia ( CLL ) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression . We conducted an international , open-label , r and omized phase 3 trial to compare two oral agents , ibrutinib and chlorambucil , in previously untreated older patients with CLL or small lymphocytic lymphoma . METHODS We r and omly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil . The primary end point was progression-free survival as assessed by an independent review committee . RESULTS The median age of the patients was 73 years . During a median follow-up period of 18.4 months , ibrutinib result ed in significantly longer progression-free survival than did chlorambucil ( median , not reached vs. 18.9 months ) , with a risk of progression or death that was 84 % lower with ibrutinib than that with chlorambucil ( hazard ratio , 0.16 ; P<0.001 ) . Ibrutinib significantly prolonged overall survival ; the estimated survival rate at 24 months was 98 % with ibrutinib versus 85 % with chlorambucil , with a relative risk of death that was 84 % lower in the ibrutinib group than in the chlorambucil group ( hazard ratio , 0.16 ; P=0.001 ) . The overall response rate was higher with ibrutinib than with chlorambucil ( 86 % vs. 35 % , P<0.001 ) . The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib . Adverse events of any grade that occurred in at least 20 % of the patients receiving ibrutinib included diarrhea , fatigue , cough , and nausea ; adverse events occurring in at least 20 % of those receiving chlorambucil included nausea , fatigue , neutropenia , anemia , and vomiting . In the ibrutinib group , four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage . A total of 87 % of the patients in the ibrutinib group are continuing to take ibrutinib . CONCLUSIONS Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma , as assessed by progression-free survival , overall survival , response rate , and improvement in hematologic variables . ( Funded by Pharmacyclics and others ; RESONATE-2 Clinical Trials.gov number , NCT01722487 . ) Abstract Health-related quality of life ( HRQoL ) is a key issue for patients with chronic lymphocytic leukemia . The multicenter LRF CLL4 trial , in which 777 patients were r and omized to receive chlorambucil or fludarabine , alone or with cyclophosphamide ( FC ) , assessed HRQoL at baseline , months 3 , 6 and 12 , then annually until 5 years , using the European Organisation for Research and Treatment of Cancer quality of life question naire ( EORTC-QLQ-C30 ) . While on treatment , some HRQoL impairment was seen in patients receiving fludarabine , particularly FC , compared with chlorambucil . Thus at 3 months , role/social functioning and fatigue were ≥ 10 points worse than baseline in 41%/46%/56 % , respectively , of patients receiving fludarabine alone and 48%/54%/60 % receiving FC , compared with only 29%/31%/40 % of those receiving chlorambucil . Thereafter HRQoL appeared similar between treatment groups . Sustained remissions were associated with long-term HRQoL benefit . In the primary HRQoL domains patients still in complete or partial remission at each time-point had scores close to those reported in general population studies , while patients whose disease had progressed had mean scores up to 22 points worse , in spite of subsequent treatments . These data offer support for the use of primary treatment regimens likely to achieve and sustain remission in otherwise medically fit patients of all ages , including those aged > 70 years BACKGROUND The monoclonal anti-CD20 antibody rituximab , combined with chemotherapeutic agents , has been shown to prolong overall survival in physically fit patients with previously untreated chronic lymphocytic leukemia ( CLL ) but not in those with coexisting conditions . We investigated the benefit of the type 2 , glycoengineered antibody obinutuzumab ( also known as GA101 ) as compared with that of rituximab , each combined with chlorambucil , in patients with previously untreated CLL and coexisting conditions . METHODS We r and omly assigned 781 patients with previously untreated CLL and a score higher than 6 on the Cumulative Illness Rating Scale ( CIRS ) ( range , 0 to 56 , with higher scores indicating worse health status ) or an estimated creatinine clearance of 30 to 69 ml per minute to receive chlorambucil , obinutuzumab plus chlorambucil , or rituximab plus chlorambucil . The primary end point was investigator-assessed progression-free survival . RESULTS The patients had a median age of 73 years , creatinine clearance of 62 ml per minute , and CIRS score of 8 at baseline . Treatment with obinutuzumab-chlorambucil or rituximab-chlorambucil , as compared with chlorambucil monotherapy , increased response rates and prolonged progression-free survival ( median progression-free survival , 26.7 months with obinutuzumab-chlorambucil vs. 11.1 months with chlorambucil alone ; hazard ratio for progression or death , 0.18 ; 95 % confidence interval [ CI ] , 0.13 to 0.24 ; P<0.001 ; and 16.3 months with rituximab-chlorambucil vs. 11.1 months with chlorambucil alone ; hazard ratio , 0.44 ; 95 % CI , 0.34 to 0.57 ; P<0.001 ) . Treatment with obinutuzumab-chlorambucil , as compared with chlorambucil alone , prolonged overall survival ( hazard ratio for death , 0.41 ; 95 % CI , 0.23 to 0.74 ; P=0.002 ) . Treatment with obinutuzumab-chlorambucil , as compared with rituximab-chlorambucil , result ed in prolongation of progression-free survival ( hazard ratio , 0.39 ; 95 % CI , 0.31 to 0.49 ; P<0.001 ) and higher rates of complete response ( 20.7 % vs. 7.0 % ) and molecular response . Infusion-related reactions and neutropenia were more common with obinutuzumab-chlorambucil than with rituximab-chlorambucil , but the risk of infection was not increased . CONCLUSIONS Combining an anti-CD20 antibody with chemotherapy improved outcomes 
    Output:
    
PFS was longer with purine analogs compared with chlorambucil with an increased risk of infection .
The risk of secondary malignancies was not increased with chlorambucil .
In conclusion , our study showed that chlorambucil is an acceptable chemotherapy backbone for unfit patients with CLL .