***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: In this prospect i ve r and omized trial , we compared the efficacy and toxicity of cladribine ( 2-CdA ) alone to 2-CdA combined with cyclophosphamide ( CC ) or cyclophosphamide and mitoxantrone ( CMC ) in untreated progressive chronic lymphocytic leukemia ( CLL ) . Study end points were complete response ( CR ) , overall response , minimal residual disease ( MRD ) , progression-free survival , overall survival , and toxicity .  From January 1 , 1998 to December 31 , 2003 , 508 patients from 15 hematology departments were r and omized . Compared with 2-CdA , CMC induced higher CR rate ( 36 % vs 21 % , P = .004 ) , and a trend for higher CR rate with CC was observed ( 29 % vs 21 % , P = .08 ) . Furthermore , the percentage of patients who were in CR and were MRD negative was higher in CMC compared with 2-CdA ( 23 % vs 14 % , P = .042 ) . There were no differences in overall response , progression-free survival , and overall survival among treatment groups . Grade 3/4 neutropenia occurred more frequently in CC ( 32 % ) and CMC ( 38 % ) than in 2-CdA ( 20 % ) ( P = .01 and P = .004 , respectively ) . Infections were more frequent in CMC compared with 2-CdA ( 40 % vs 27 % , P = .02 ) . In conclusion , CMC used in first-line treatment of CLL results in a higher CR rate and suppresses MRD more efficiently than 2-CdA monotherapy , although associates with increased toxicity . No important differences in efficacy and toxicity were found between CC and 2-CdA regimens 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 Abstract : Objectives : Therapeutic results in advanced chronic lymphocytic leukemia ( CLL ) are still unsatisfactory in terms of complete remission achievement and duration , in spite of the extensive use of purine analogs . The objective of this study was to describe the clinical characteristics and treatment results from a series of 32 patients managed with a therapeutic program based on the combination of fludarabine and cyclophosphamide ( CTX ) PURPOSE Richter 's syndrome ( RS ) and fludarabine-refractory chronic lymphocytic leukemia ( CLL ) are associated with poor clinical outcomes . We conducted a phase I-II trial of oxaliplatin , fludarabine , cytarabine , and rituximab ( OFAR ) in these diseases . PATIENTS AND METHODS The OFAR regimen consisted of increasing doses of oxaliplatin ( 17.5 , 20 , or 25 mg/m(2)/d ) on days 1 to 4 ( phase I ) , fludarabine 30 mg/m(2 ) on days 2 to 3 , cytarabine 1 g/m(2 ) on days 2 to 3 , rituximab 375 mg/m(2 ) on day 3 of cycle 1 and day 1 of subsequent cycles , and pegfilgrastim 6 mg on day 6 , every 4 weeks for a maximum of six courses . Dose-limiting toxicity ( DLT ) was defined as any nonhematologic , treatment-related toxicity > /= grade 3 . RESULTS Fifty patients were treated ( 20 patients had RS , and 30 had CLL ) . The highest tolerated oxaliplatin dose was 25 mg/m(2 ) , which was the highest dose tested . DLT was not observed . Pharmacodynamic analyses demonstrated enhanced leukemia cell killing by oxaliplatin in the presence of fludarabine and cytarabine . The overall response rates were 50 % in RS and 33 % in fludarabine-refractory CLL . The overall response rate  in 14 patients with age > /= 70 years was 50 % . Responses were achieved in seven ( 35 % ) of 20 patients with 17p deletion , two ( 29 % ) of seven patients with 11q deletion , all four patients with trisomy 12 , and two ( 40 % ) of five patients with 13q deletion . The median response duration was 10 months . Toxicities were mainly hematologic ; prolonged myelosuppression was not observed . CONCLUSION The OFAR regimen is highly active in RS and has activity in fludarabine-refractory patients with CLL . This regimen warrants further investigation in the treatment of these disorders The efficacy and toxicity of cladribine ( 2-CdA ) + prednisone ( P ) versus chlorambucil ( Chl ) + P were compared in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia ( CLL ) in a r and omized , multicenter prospect i ve trial . Eligible patients were assigned to either 2-CdA 0.12 mg/kg per day in 2-hour infusions and P 30 mg/m(2 ) per day for 5 consecutive days or Chl 12 mg/m(2 ) per day and P 30 mg/m(2 ) per day for 7 consecutive days . Three courses were administered at 28-day intervals or longer if myelosuppression developed . The therapy was finished if complete response ( CR ) was achieved . Of 229 available patients 126 received 2-CdA+P and 103 received Chl+P as a first-line treatment . CR and overall response rates were significantly higher in the patients treated with 2-CdA+P ( 47 % and 87 % , respectively ) than in the patients treated with Chl+P ( 12 % and 57 % , respectively ) ( P = .001 ) . Progression-free survival was significantly longer in the 2-CdA-treated group ( P = .01 ) , but event-free survival was not statistically different . Thirteen percent of patients were refractory to 2-CdA+P and 43 % to Chl+P ( P = .001 ) . Drug-induced neutropenia was more frequently observed during 2-CdA+P ( 23 % ) than Chl+P therapy ( 11 % ) ( P = .02 ) , but thrombocytopenia occurred with similar frequency in both groups ( 36 % and 27 % , respectively ) . Infections were seen more frequently in the 2-CdA+P-treated group ( 56 % ) than in the Chl+P-treated group ( 40 % ; P = .02 ) . Death rates have so far been similar in patients treated with 2-CdA ( 20 % ) and with Chl ( 17 % ) . The probability of overall survival calculated from Kaplan-Meier curves at 24 months was also similar for both groups ( 78 % and 82 % , respectively ) . ( Blood . 2000;96:2723 - 2729 Purpose : Flavopiridol has in vitro activity in chronic lymphocytic leukemia ( CLL ) and promotes apoptosis independent of p53 function or prior fludarabine exposure . We sought to determine if flavopiridol has activity in previously treated CLL using two schedules of administration . Patients and Methods : Patients with previously treated CLL were enrolled in two sequentially done phase II studies . Patients in the first trial received flavopiridol ( 50 mg/m2/d ) as a continuous infusion ( CI ) for 72 hours every 2 weeks . Patients in the second trial received flavopiridol 50 mg/m2 as a 1-hour bolus ( IVB ) daily for 3 days repeated every 3 weeks . Patients received up to 12 ( CI cohort ) or 8 ( IVB cohort ) cycles of therapy . Results : Fifteen patients were enrolled in the 72-hour CI phase II trial ; 6 ( 40 % ) had intermediate-risk ( Rai stage I or II ) and 9 ( 60 % ) had high-risk ( Rai stage III and IV ) stages . No responses were noted in this group ; 27 % had stable disease and 73 % had progressive disease . Thirty-six patients were enrolled in the second IVB trial , with 13 ( 36 % ) having intermediate and 23 ( 64 % ) having high-risk disease . Four patients ( 11 % ) had partial responses , 19 ( 53 % ) had stable disease , and 13 ( 36 % ) had progressive disease . The progression-free survival for responders in the IVB trial was 3 , 3 , 9 , and 19 months . The median progression-free survival was 2 months [ 95 % confidence interval ( 95 % CI ) , 1.8 - 3.8 ] for patients in the CI trial and 3 months ( 95 % CI , 2.5 - 7.4 ) for the IVB trial . The median overall survival was 27 months ( 95 % CI , 20 - 42 ) for the CI trial and 24 months ( 95 % CI , 18 - 31 ) for the IVB trial . Toxicity was manageable and included mainly myelosuppression , infections , diarrhea , and fatigue . Conclusions : Flavopiridol has modest , schedule-dependent clinical activity in relapsed CLL and warrants future investigation utilizing alternative schedules of administration To comparatively assess first-line treatment with fludarabine and 2 anthracycline-containing regimens , namely CAP ( cyclophosphamide , doxorubicin plus prednisone ) and ChOP ( cyclophosphamide , vincristine , prednisone plus doxorubicin ) , in advanced stages of chronic lymphocytic leukemia ( CLL ) , previously untreated patients with stage B or C CLL were r and omly allocated to receive 6 monthly courses of either ChOP , CAP , or fludarabine ( FAMP ) , stratified based on the Binet stages . End points were overall survival , treatment response , and tolerance .  From June 1 , 1990 to April 15 , 1998 , 938 patients ( 651 stage B and 287 stage C ) were r and omized in 73 centers . Compared to ChOP and FAMP , CAP induced lower overall remission rates ( 58.2 % ; ChOP , 71.5 % ; FAMP ; 71.1 % ; P < .0001 for each ) , including lower clinical remission rates ( CAP , 15.2 % ; ChOP , 29.6 % ; FAMP , 40.1 % ; P = .003 ) . By contrast , median survival time did not differ significantly according to r and omization ( 67 , 70 , and 69 months in the ChOP , CAP , and FAMP groups , respectively ) . Incidences of infections ( < 5 % ) and autoimmune hemolytic anemia ( < 2 % ) during the 6 courses were similar in the r and omized groups , whereas fludarabine induced , compared to ChOP and CAP , more frequent protracted thrombocytopenia ( P = .003 ) and less frequent nausea-vomiting ( P = .003 ) and hair loss ( P < .0001 ) . For patients with stage B and C CLL first-line fludarabine and ChOP regimens both provided similar overall survival and close response rates , and better results than CAP . However , there was an increase in clinical remission rate and a trend toward a better tolerance of fludarabine over ChOP that may influence the choice between these regimens as front-line treatments in patients with CLL This study investigated the efficacy , safety , and clinical benefit of alemtuzumab ( Campath-1H ) for patients with relapsed or refractory B-cell chronic lymphocytic leukemia exposed to alkylating agents and having failed fludarabine therapy . Ninety-three patients received alemtuzumab in 21 centers worldwide , with the aim to obtain an overall response rate of at least 20 % . 
    Output:
    
A significant correlation between median pfs or ttp and median os was observed in second- and subsequent-line therapies , but not in the first-line setting .
Our study demonstrates a strong correlation between median pfs or ttp and median os in previously treated cll , which reinforce the hypothesis that pfs and ttp could be adequate surrogate endpoints for os in this cancer setting