***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 To compare the efficacy of cediranib ( a vascular endothelial growth factor receptor tyrosine kinase inhibitor [ VEGFR TKI ] ) with that of bevacizumab ( anti-VEGF-A monoclonal antibody ) in combination with chemotherapy as first-line treatment for advanced metastatic colorectal cancer ( mCRC ) . PATIENTS AND METHODS HORIZON III [ Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer ] had an adaptive phase II/III design . Patients r and omly assigned 1:1:1 received mFOLFOX6 [ oxaliplatin 85 mg/m(2 ) and leucovorin 400 mg/m(2 ) intravenously followed by fluorouracil 400 mg/m(2 ) intravenously on day 1 and then continuous infusion of 2,400 mg/m(2 ) over the next 46 hours every 2 weeks ] with cediranib ( 20 or 30 mg per day ) or bevacizumab ( 5 mg/kg every 14 days ) . An independent end-of-phase II analysis concluded that mFOLFOX6/cediranib 20 mg met predefined criteria for continuation ; subsequent patients received mFOLFOX6/cediranib 20 mg or mFOLFOX6/bevacizumab ( r and omly assigned 1:1 ) . The primary objective was to compare progression-free survival ( PFS ) . RESULTS In all , 1,422 patients received mFOLFOX6/cediranib  20 mg ( n = 709 ) or mFOLFOX6/bevacizumab ( n = 713 ) . Primary analysis revealed no significant difference between arms for PFS ( hazard ratio [ HR ] , 1.10 ; 95 % CI , 0.97 to 1.25 ; P = .119 ) , overall survival ( OS ; HR , 0.95 ; 95 % CI , 0.82 to 1.10 ; P = .541 ) , or overall response rate ( 46.3 % v 47.3 % ) . Median PFS and OS were 9.9 and 22.8 months for mFOLFOX6/cediranib and 10.3 and 21.3 months for mFOLFOX6/bevacizumab . The PFS upper 95 % CI was outside the predefined noninferiority limit ( HR < 1.2 ) . Common adverse events with more than 5 % incidence in the cediranib arm included diarrhea , neutropenia , and hypertension .  Cediranib-treated patients completed fewer chemotherapy cycles than bevacizumab-treated patients ( median 10 v 12 cycles ) . Patient-reported outcomes ( PROs ) were significantly less favorable in cediranib-treated versus bevacizumab-treated patients ( P < .001 ) . CONCLUSION Cediranib activity , in terms of PFS and OS , was comparable to that of bevacizumab when added to mFOLFOX6 ; however , the predefined boundary for PFS noninferiority was not met . The cediranib  safety profile was consistent with previous studies but led to less favorable PROs compared with bevacizumab . Investigation of oral TKIs in CRC continues BACKGROUND A week on/week off capecitabine schedule with oxaliplatin/bevacizumab was evaluated in patients with metastatic colorectal cancer ( mCRC ) . PATIENTS AND METHODS Forty patients were required . The projected median progression-free survival ( PFS ) was 12 months ( 81 % power , 1-sided level 0.1 log-rank test ) . Capecitabine dose was 2500 mg/m(2)/day on days 1 - 7 ( n = 11 ) and was increased to 3000 mg/m(2)/day ( n = 29 ) in combination with oxaliplatin ( 85 mg/m(2 ) ) and bevacizumab ( 5 mg/kg ) . Cycles were repeated every 2 weeks . RESULTS Patient characteristics included Eastern Cooperative Oncology Group ( ECOG ) performance status 0 ( n = 24 ) or 1 ( n = 15 ) ; median age of 62 years ( range , 38 - 81 years ) . Median cycles administered were 7 ( range , 125 ) , corresponding to 3.5 months ' treatment duration . Pertinent grade 3/4 toxicities seen were diarrhea ( 18 % ) , h and -foot syndrome ( 10 % ) , and peripheral neuropathy ( 10 % ) . Bowel perforation in 1 patient ( 3 % ) and 1 death due to a cerebral hemorrhage ( 3 % ) were noted . Response rate ( RR ) was 38 % ( 1 complete and 14 partial responses ) . Median PFS was 8.6 months ( 95 % confidence interval [ CI ] , 4.7 - 10.2 months ) . Median overall survival was 17.2 months ( 95 % CI , 10.4 - 24.2 months ) . CONCLUSION The first US experience of capecitabine to our knowledge ( 3000 mg/m(2 ) on days 1 - 7 ) in combination with oxaliplatin/bevacizumab in mCRC does not appear to have advantages compared with current st and ard first-line mCRC treatment regimens Purpose The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival ( PFS ) in patients with metastatic colorectal cancer ( CRC ) . An increased risk of arterial thromboembolic events has been observed in some trials in older patients , and the potential benefit of a maintenance therapy with bevacizumab alone has not been clearly demonstrated . This phase II study was design ed to evaluate the efficacy and safety of XELOX ( capecitabine plus oxaliplatin ) plus bevacizumab followed by bevacizumab alone in elderly patients with advanced CRC . Methods Treatment consisted of bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1 , plus capecitabine 1,000 mg/m2 twice daily on days 1–14 , every 3 weeks up to a maximum of 8 cycles . Patients then received maintenance therapy consisting of bevacizumab alone ( 7.5 mg/kg ) once every 3 weeks up to disease progression . The primary study end-points were safety and response rate . Results A total of 44 patients were recruited . In an intention-to-treat analysis , the overall response rate was 52 % [ 95 % confidence interval ( CI ) 37 to 68 % ] , with 86 % of patients achieving disease control . Median PFS and overall survival were 11.5 months ( 95 % CI 10.0–12.9 months ) and 19.3 months ( 95 % CI 16.5–22.1 months ) , respectively . In all , 10 patients ( 23 % ) had grade 3/4 adverse events ( AEs ) , the most common being diarrhea ( 9 % ) , neutropenia ( 7 % ) , peripheral neuropathy ( 7 % ) , and stomatitis ( 7 % ) . No patients died because of treatment-related AEs . The rate of  bevacizumab-related AEs ( hypertension , thromboembolic events , and gastrointestinal perforation ) was consistent with that reported earlier in the general CRC population . Conclusion The combination of XELOX and bevacizumab is effective and has a manageable tolerability profile when administered to elderly patients with advanced CRC . Maintenance therapy with single-agent bevacizumab may be considered to extend PFS in this setting of patients Summary Purpose To assess safety and efficacy of folinic acid , 5-fluorouracil , gemcitabine ( FFG ) and folinic acid , fluorouracil , oxaliplatin ( FOLFOX4 ) regimens with added bevacizumab as first-line treatment in patients with advanced colorectal cancer ( CRC ) . Patients and Methods Patients with Stage III unresectable or Stage IV adenocarcinoma of the colon or rectum were r and omly assigned to either FFG weekly for 6 weeks of an 8-week cycle or FOLFOX4 every 2 weeks . After FDA approval , bevacizumab 5 mg/kg was added every 2 weeks . Treatment continued until disease progression . Planned enrollment was 190 patients . Primary endpoint was overall response rate ( ORR ) ; secondary endpoints included evaluation of adverse events , time to progression ( TTP ) , and overall survival ( OS ) . Disease Control Rate ( DCR ; % of patients with complete or partial responses or stable disease ) was a post hoc analysis . Results The trial was stopped prematurely due to low enrollment . Of 84 enrolled patients ( 42 to each arm ) , 36 patients ( 18 in each arm ) received  bevacizumab .  ORR was greater ( P = .002 ) for FOLFOX4 ( 17/42 ; 40.5 % ) than for FFG ( 4/42 ; 9.5 % ) ; however , TTP , OS , and DCR results were not statistically different comparing FOLFOX4 and FFG . Peripheral neuropathy was more frequent ( P = < .001 ) with FOLFOX4 ( 18/42 ; 42.9 % ) than with FFG ( 1/42 ; 2.4 % ) . Conclusions FFG and FOLFOX4 were generally well tolerated . Based on ORR , FOLFOX4 was superior to FFG . However , differences in TTP and OS comparing regimens were inconclusive . General use of gemcitabine as a biomodulator of 5-fluorouracil in CRC can not be recommended at this time and the regimen remains investigational BACKGROUND Cetuximab ( C ) , alone or with irinotecan , demonstrates activity in irinotecan-refractory colorectal cancer ( CRC ) . Activity of 5-fluorouracil ( 5-FU ) , leucovorin ( L ) , and bevacizumab ( B ) , and preliminary data of cetuximab + bevacizumab , and toxicity profiles suggests that FOLF-CB ( 5-FU , L , C+B ) may have activity with a favorable toxicity profile as first-line therapy . METHODS Eligible patients were r and omized at registration to either arm A ( mFOLFOX6-B ) ( modified , 5-FU . L ( folinic acid ) , oxaliplatin ( O ) + bevacizumab ) , administered days 1 and 15 of each 28-day cycle as bevacizumab 5 mg/kg , oxaliplatin 85 mg/m(2 ) , leucovorin 400 mg/m(2 ) , and 5-FU 400 mg/m(2 ) then 1200 mg/m(2)/day for 48 hours , or arm B ( FOLF-CB ) , which included bevacizumab , leucovorin , and 5-FU as in arm A and cetuximab 400 mg/m(2 ) day 1 cycle 1 ; all other weekly cetuximab doses were 250 mg/m(2 ) . RESULTS Two hundred forty-seven patients ( arm A/arm B 124/123 ) were enrolled , and 239 were treated ( 118/121 ) .  Twelve-month progression-free survival ( PFS ) was 45%/32 % , objective response rates ( ORR ) ( complete response [ CR ] + partial response [ PR ] ) were 52%/41 % , disease control rates ( CR+PR+stable disease [ SD ] ) were 87%/83 % , and median overall survival ( OS ) was 21/19.5 months , respectively . Grade 3 - 4 neutropenia was higher in arm A ( 28%/7 % ) , as was grade 3 fatigue ( 12%/3 % ) , and grade 3 neuropathy ( 11%/ < 1 % ) , whereas acneiform rash was confined to arm B. Retrospective analysis of KRAS mutational status did not demonstrate KRAS as a meaningful determinant of activity , except in arm B patients with KRAS-mutated tumors , which result ed in inferior PFS . Patient satisfaction favored the control ( mFOLFOX6-B ) . CONCLUSION FOLF-CB was not superior to mFOLFOX6-B in terms of 12-month PFS and ORR , and was not more acceptable to patients . This trial supports the conclusion of other recently reported trials that concurrent cetuximab+bevacizumab should not be routinely used in metastatic CRC 
    Output:
    
XELOX + B and FOLFOX + B are active combinations as first-line treatment of advanced CRC .
Both the XELOX + B and the FOLFOX + B arms represent 2 of the cornerstone combinations when B is used as first-line therapy