***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: BACKGROUND We evaluated the activity and toxic effects of bortezomib in patients with mantle cell lymphoma . PATIENTS AND METHODS Thirty patients , including 29 eligible patients , were enrolled ; 13 had received no prior chemotherapy . The dose of bortezomib was 1.3 mg/m2 given on days 1 , 4 , 8 and 11 every 21 days . Response was assessed according to the International Workshop Criteria for non-Hodgkin 's lymphoma and toxicity grade d using the National Cancer Institute Common Toxicity Criteria version 2.0 . RESULTS There were 13 responding patients ( 46.4 % ; 95 % confidence interval=27.5 % to 66.1 % ) , including one unconfirmed complete remission . The median response duration was 10 months . Response rates were similar in previously untreated ( 46.2 % ) and treated ( 46.7 % ) patients . Neurological toxicity and myalgia led to treatment discontinuation in 10 patients after two to seven treatment cycles . Five serious adverse events ( including two deaths ) associated with fluid retention were observed in the first 12 patients . We subsequently excluded patients with baseline effusions , dyspnea or edema ; no further events were seen . CONCLUSIONS Bortezomib is active in treating patients with mantle cell lymphoma . While cumulative neuromuscular toxic effects limited therapy duration and specific issues related to fluid retention require further evaluation , continued study of this drug in combination regimens is warranted PURPOSE Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin 's lymphoma . PATIENTS AND METHODS Patients were stratified , based on pre clinical data , into arm A ( mantle-cell lymphoma ) or arm B ( other B-cell lymphomas ) without limitation in number of prior therapies . Bortezomib was administered as an intravenous push ( 1.5 mg/m2 ) on days 1 , 4 , 8 , and 11 every 21 days for a maximum of six cycles . RESULTS Sixty patients with a median number of prior therapies of 3.5 ( range , one to 12 therapies ) were enrolled ; 33 patients were in arm A and 27 were in arm B , including 12 diffuse large B-cell lymphomas , five follicular lymphomas ( FL ) , three transformed FLs , four small lymphocytic lymphomas ( SLL ) , two Waldenstrom 's macroglobulinemias ( WM ) , and one marginal zone lymphoma . In arm A , 12 of 29 assessable patients responded ( six complete responses [ CR ] and six partial responses [ PR ] ) for an overall response rate ( ORR ) of 41 % ( 95 % CI , 24 % to 61 % ) , and a median time to progression not reached yet , with a median follow-up of 9.3 months ( range , 1.7 to 24 months ) . In arm B , four of 21 assessable patients responded ( one SLL patient had a CR , one FL patient had a CR unconfirmed , one diffuse large B-cell lymphoma patient had a PR , and one WM patient had a PR ) for an ORR of 19 % ( 95 % CI , 5 % to 42 % ) . Grade 3 toxicity included thrombocytopenia ( 47 % ) , gastrointestinal ( 20 % ) , fatigue ( 13 % ) , neutropenia ( 10 % ) , and peripheral neuropathy ( 5 % ) . Grade 4 toxicity occurred in nine patients ( 15 % ) , and three deaths from progression of disease occurred within 30 days of withdrawal from study . CONCLUSION Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas . Future studies will explore bortezomib in combination with other cytotoxic or biologic agents Background The r and omized phase 3 LYM3001 trial in relapsed follicular lymphoma ( FL ) demonstrated higher overall ( ORR ) and complete response ( CR ) rates and prolonged progression-free survival ( PFS ) with bortezomib-rituximab versus rituximab . We report findings in high-risk patients ( FL International Prognostic Index [ FLIPI ] score ≥3 , and high tumor burden by modified Groupe d’Etude des Lymphomas Folliculaires [ GELF ] criteria ) . Methods Patients aged ≥18 years with grade 1/2 FL , ≥1 measurable lesion , and documented relapse or progression following prior therapy , rituximab-naïve or rituximab-sensitive , were enrolled at 164 centers in 29 countries across Europe , the Americas , and Asia-Pacific . Patients were r and omized ( 1:1 ) to five 5-week cycles of bortezomib-rituximab ( bortezomib 1.6 mg/m2 , days 1 , 8 , 15 , and 22 , all cycles ; rituximab 375 mg/m2 , days 1 , 8 , 15 , and 22 , cycle 1 , and day 1 , cycles 2–5 ; N=336 ) or rituximab alone ( N=340 ) . R and omization was stratified by FLIPI score , prior rituximab , time since last dose of anti-lymphoma therapy , and geographical region . The primary endpoint of the study was PFS . Results  103 bortezomib-rituximab and 98 rituximab patients had high-risk FL . The ORR was 59 % versus 37 % ( p=0.002 ) , the CR/CRu rate was 13 % versus 6 % ( p=0.145 ) , and the durable response rate was 45 % versus 26 % ( p=0.008 ) with bortezomib-rituximab versus  rituximab . Median PFS was 9.5 versus 6.7 months ( hazard ratio [ HR ] 0.667 , p=0.012 ) with bortezomib-rituximab versus rituximab ; median time to progression was 10.9 versus 6.8 months ( HR 0.656 , p=0.009 ) ; median time to next anti-lymphoma treatment was 14.8 versus 9.1 months ( HR 0.762 , p=0.103 ) ; and the 1-year Overall Survival rate was 83.1 % versus 76.6 % . Overall , 51 % of bortezomib-rituximab and 32 % of rituximab patients reported grade ≥3 adverse events , including neutropenia ( 18 % , 6 % ) , anemia ( 4 % , 5 % ) , diarrhea ( 8 % , 0 % ) , thrombocytopenia ( 5 % , 2 % ) , and sensory neuropathy ( 1 % , 0 % ) . Conclusions High-risk FL patients treated with bortezomib-rituximab had significantly higher ORR and longer PFS than patients receiving rituximab alone , with greater clinical benefit than in the overall study population ; additional toxicity was acceptable and did not affect treatment feasibility . Trial registration The phase 3 LYM3001 trial is registered with Clinical Trials.gov , with the identifier NCT00312845 PURPOSE Bortezomib has previously demonstrated activity in indolent lymphomas including follicular lymphoma with response rate ranging from 13 % to 56 % . However , the optimal schedule of bortezomib remains to be investigated in follicular lymphoma . EXPERIMENTAL DESIGN We conducted a r and omised phase II study where patients with follicular lymphoma in relapse or refractory receive either bortezomib 1.5 mg/m(2 ) biweekly on days 1 , 4 , 8 and 11 of a 21-day cycle ( arm A ) or 1.6 mg/m(2 ) weekly on days 1 , 8 , 15 and 22 of a 35-day cycle ( arm B ) . An interim analysis was planned after 15 fully evaluable patients r and omised in each treatment arm . If only five subjects or fewer respond , the treatment arm was concluded to be ineffective and was closed to inclusion . RESULTS Eighty-seven patients were included in the trial . Arm B was closed to inclusion after interim analysis . 15/50 patients ( 30 % ) in arm A and 8/37 patients ( 22 % ) in arm B achieved a response . Median duration of response was 16 and 15 months for arms A and B , respectively . Most drug-related adverse events ( AEs ) ( all grade s , all cycles ) were mild . CONCLUSION This study demonstrates tolerability and durable clinical benefit of bortezomib when given at 1.5 mg/m(2 ) biweekly . Despite a higher response rate in the biweekly arm , no major difference in patient 's outcome was observed between the two arms in the final analysis Purpose : To determine the safety and efficacy of substituting weekly or twice-weekly bortezomib for vincristine in the R-CVP ( rituximab , cyclophosphamide , vincristine , and prednisone ) regimen in patients with relapsed/refractory indolent and mantle cell lymphoma ( MCL ) . Experimental Design : Of the 57 patients in this phase I trial , 55 participated in 1 of 2 dosing schedules that included rituximab ( 375 mg/m2 ) and cyclophosphamide ( 750 or 1,000 mg/m2 ) administered on day 1 of each 21-day cycle and prednisone ( 100 mg orally ) days 2 to 6 . In the once-weekly schedule , bortezomib was administered on days 2 and 8 ; on the twice-weekly schedule , bortezomib was given on days 2 , 5 , 9 , and 12 . Bortezomib and cyclophosphamide were alternately escalated . A separate cohort of 10 patients in the twice-weekly schedule received concurrent pegfilgrastim ( PegG ) on day 2 . Results : Both schedules of R-CBorP ( rituximab , cyclophosphamide , bortezomib , and prednisone ) were well tolerated . Most toxicities across all dose levels and cycles were grade 1 or 2 . The overall response rates for patients on the weekly ( n = 13 ) and twice-weekly ( n = 33 ) schedules were 46 % [ 23 % complete response/complete response unconfirmed ( CR/CRu ) ] and 64 % ( 36 % CR/CRu ) , respectively . Concurrent PegG did not increase hematologic toxicities in this regimen . A r and omized phase II study is under way to further compare toxicity and efficacy of the 2 dosing schedules . Conclusions : R-CBorP is a safe and effective regimen in patients with relapsed/refractory indolent and MCLs . Most toxicities were grade 1 or 2 , and a promising response rate was seen in this phase I study . Clin Cancer Res ; 17(8 ) ; 2493–501 . © 2011 AACR OBJECTIVE To evaluate the efficacy and toxicity of the combination of VRCD ( velcade/rituximab/cyclophosphamide/dexamethasone ) in chemotherapy-naïve low- grade non-Hodgkin lymphoma or patients with transplantation-ineligible mantle cells . METHODS The patients were treated with velcade , at 1.6 mg/m(2 ) , on days 1 , 8 , 15 , and 22 on every 35-day cycle . Rituximab was given at 375 mg/m(2 ) on the same days as velcade during cycle 1 and then only on day 1 in subsequent cycles . Dexamethasone was given orally at 40 mg on days 1 , 2 , 8 , 9 , 15 , 16 , 22 , and 23 . Cyclophosphamide was administered orally at 400 mg/m(2 ) on days 1 - 4 . The patients had to meet criteria to initiate therapy and had to demonstrate adequate performance status and organ function . RESULTS Twelve patients were enrolled , after which the study was closed due to a lack of funding . The median age was 68 years ( 37 - 83 years ) , with 83 % having stage III/IV disease . Five patients had marginal zone , 4 had follicular , 2 had small lymphocytic , and 1 had mantle cell histologies . The overall response rate was 90 % ( complete response , 54 % ) . At a median follow-up of 22 months , 9 ( 75 % ) patients remain alive , and the median time to progression has not been reached . A third of the patients required dose reductions after a median of 6.5 cycles . No grade 3 or 4 peripheral neuropathy was witnessed . CONCLUSIONS Although the number of studied patients is small , VRCD appears safe and active as front-line therapy for low- grade non-Hodgkin lymphoma . Further studies are justified Given the significant activity and tolerability of bendamustine , rituximab , and bortezomib in patients with relapsed indolent and mantle cell non-Hodgkin lymphoma , and laboratory studies suggesting synergistic activity , 
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Furthermore , there were no significant differences between the two schedules of bortezomib for the main adverse events .
Interpretation The biweekly schedule of bortezomib was more effective than the weekly schedule in indolent lymphoma , with similar proportion of toxicities