***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 Total mesorectal excision with fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy is a st and ard treatment of locally advanced rectal cancer . This study investigated the addition of oxaliplatin with and without preoperative radiotherapy . METHODS In this multicenter , open-label , phase III trial , we r and omly assigned ( 1:1:1 ) Chinese adults ( age 18 to 75 years ) with locally advanced stage II/III rectal cancer to three treatments : five 2-week cycles of infusional fluorouracil ( leucovorin 400 mg/m(2 ) , fluorouracil 400 mg/m(2 ) , and fluorouracil 2.4 g/m(2 ) over 48 h ) plus radiotherapy ( 46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 through 4 ) followed by surgery and seven cycles of infusional fluorouracil , the same treatment plus intravenous oxaliplatin 85 mg/m(2 ) on day 1 of each cycle ( modified FOLFOX6 [ mFOLFOX6 ] ) , or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6 . R and om assignment was performed by using computer-generated block r and omization codes . The primary end point was 3-year disease-free survival . Secondary end points of histopathologic response and toxicity are reported . RESULTS A total of 495 patients were enrolled from June 2010 to February 2015 ; 475 were evaluable  ( fluorouracil-radiotherapy , n = 155 ; mFOLFOX6-radiotherapy , n = 157 ; mFOLFOX6 , n = 163 ) . In the fluorouracil-radiotherapy , mFOLFOX6-radiotherapy , and mFOLFOX6 groups , the rate of pathologic complete response ( pCR ) was 14.0 % , 27.5 % , and 6.6 % , and downstaging ( ypStage 0 to 1 ) was achieved by 37.1 % , 56.4 % , and 35.5 % of patients , respectively . Higher toxicity and more postoperative complications were observed in patients who received radiotherapy . CONCLUSION mFOLFOX6-based preoperative chemoradiotherapy results in a higher pCR rate  than fluorouracil-based treatment . Perioperative mFOLFOX6 alone had inferior results and a lower pCR rate than chemoradiotherapy but led to a similar downstaging rate as fluorouracil-radiotherapy , with less toxicity and fewer postoperative complications PURPOSE The purpose of this study was to evaluate the rate of pathologic complete response ( pCR ) in patients with locally advanced rectal cancer ( LARC ) treated with neoadjuvant chemoradiation therapy ( CRT ) with leucovorin ( FL ) versus irinotecan/S-1 ( IS ) . METHODS AND MATERIAL S Patients with resectable LARC ( clinical stage T3/4 , lymph node positive , or both ) were r and omly assigned to receive preoperative radiation ( 45 - 50.4 Gy in 25 to 28 daily fractions ) and concomitant chemotherapy either with a bolus injection of FL ( 400 mg/m(2)/day 5-fluorouracil and 20 mg/m(2)/day leucovorin ) for 3 consecutive days every 4 weeks for 2 cycles ( FL group ) or with 40 mg/m(2 ) irinotecan on days 1 , 8 , 15 , 22 , and 29 , and 35 mg/m(2 ) S-1 twice on the day of irradiation ( IS group ) . Curative surgery was performed approximately 4 to 8 weeks after the completion of CRT . The postoperative chemotherapy regimen was FL with a primary endpoint of a pCR rate evaluation . RESULTS One hundred forty-two eligible patients were r and omly assigned , and the median follow-up duration was 43.8 months ( 95 % confidence interval , 40.8 - 46.8 months ) . One hundred thirty-three patients ( 93.7 % ) of 142 underwent total mesorectal excision ; pCR was achieved in 11 ( 16.7 % ) of 66 patients in the FL group and 17 ( 25.8 % ) of 67 patients in the IS group ( P=.246 ) . When good responders were defined as patients with M and ard grade s 1 and 2 , the rate of good responders was significantly higher in the IS group than in the FL group ( 54.6 % vs 36.4 % , respectively , P=.036 ) . The preoperative rates of grade 3 and 4 toxicities were higher in the IS group ( 7.0 % ) than in the FL group ( 1.4 % , P=.095 ) . The 3-year disease-free survival was not significantly different between the 2 groups ( 79.7 % vs 76.6 % , respectively , P=.896 ) . CONCLUSIONS IS-based preoperative CRT did not increase pCR rate , but it did increase acute toxicities compared with st and ard 5-FU treatment . Therefore , further investigation is needed Clinical trials investigating the effects of addition of oxaliplatin to neoadjuvant radiochemotherapy in locally advanced rectal cancers ( LARCs ) have brought controversial results for pathologic complete response as an endpoint . This r and omized clinical trial investigated downstaging as a short‐term surrogate for progression‐free survival ( PFS ) PURPOSE Three-year disease-free survival ( DFS ) was significantly improved in patients who had undergone resection with curative intent for stage II or III colon cancer who received bolus plus continuous-infusion fluorouracil plus leucovorin ( LV5FU2 ) with the addition of oxaliplatin ( FOLFOX4 ) . Final results of the study , including 6-year overall survival ( OS ) and 5-year up date d DFS , are reported . PATIENTS AND METHODS A total of 2,246 patients were r and omly assigned to receive LV5FU2 or FOLFOX4 for 6 months . The primary end point was DFS . Secondary end points were OS and safety . Results Five-year DFS rates were 73.3 % and 67.4 % in the FOLFOX4 and LV5FU2 groups , respectively ( hazard ratio [ HR ] = 0.80 ; 95 % CI , 0.68 to 0.93 ; P = .003 ) . Six-year OS rates were 78.5 % and 76.0 % in the FOLFOX4 and LV5FU2 groups , respectively ( HR = 0.84 ; 95 % CI , 0.71 to 1.00 ; P = .046 ) ; corresponding 6-year OS rates for patients with stage III disease were 72.9 % and 68.7 % , respectively ( HR = 0.80 ; 95 % CI , 0.65 to 0.97 ; P = .023 ) . No difference in OS was seen in the stage II population . The incidence of second noncolorectal cancers was 5.5 % and 6.1 % in the FOLFOX4 and LV5FU2 groups , respectively . Among patients receiving oxaliplatin , the frequency of grade 3 peripheral sensory neuropathy was 1.3 % 12 months after treatment and 0.7 % at 48 months . CONCLUSION Adding oxaliplatin to LV5FU2 significantly improved 5-year DFS and 6-year OS in the adjuvant treatment of stage II or III colon cancer and should be considered after surgery for patients with stage III disease Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background In locally advanced rectal cancer ( LARC )  preoperative chemoradiation ( CRT ) is the st and ard of care , but the risk of local recurrence is low with good quality total mesorectal excision ( TME ) , although many still develop metastatic disease . Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease . Neoadjuvant systemic chemotherapy ( NACT ) alone may reduce local and systemic recurrences , and may be more effective than postoperative treatments which often have poor compliance . Investigation of intensified NACT is warranted to improve outcomes for patients with LARC . The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection . Methods / design This is a multi-centre , r and omized phase II trial . Eligible patients must have histologically confirmed LARC with distal part of the tumour 4–12 cm from anal verge , no metastases , and poor prognostic features on pelvic MRI . Sixty patients will be r and omly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin ( FOLFOX ) + bevacizumab ( BVZ ) or FOLFOX + irinotecan ( FOLFOXIRI ) + BVZ , given in 2 weekly cycles for up to 6 cycles prior to TME . Patients stop treatment if they fail to respond after 3 cycles ( defined as ≥ 30 % decrease in St and ardised Uptake Value ( SUV ) compared to baseline PET/CT).The primary endpoint is pathological complete response rate . Secondary endpoints include objective response rate , MRI tumour regression grade , involved circumferential resection margin rate , T and N stage downstaging , progression-free survival , disease-free survival , overall survival , local control , 1-year colostomy rate , acute toxicity , compliance to chemotherapy . Discussion In LARC , a neoadjuvant chemotherapy regimen - if feasible , effective and tolerable would be suitable for testing as the novel arm against the current st and ards of short course preoperative radiotherapy ( SCPRT ) and /or fluorouracil (5FU)-based CRT in a future r and omised phase III trial . Trial registration Clinical trial identifier BACCHUS : BACKGROUND Whether there is any benefit derived from adding oxaliplatin to fluoropyrimidine-based preoperative chemoradiation is currently unknown in cases of advanced cT3 or cT4 tumours . Our aim was to evaluate this issue by analysing a r and omized trial , which compared two schedules of preoperative treatment ( chemoradiation vs. 5 × 5 Gy with 3 cycles of consolidation chemotherapy ) for cT4 or fixed cT3 rectal cancer . PATIENTS AND METHODS Delivery of oxaliplatin was m and atory to the first part of the study . For the second part , its delivery in both treatment-assigned groups was left to the discretion of the local investigator . We analysed a subgroup of 272 patients ( 136 in the oxaliplatin group and 136 in the fluorouracil-only group ) from institutions that had omitted oxaliplatin in the second part of the study .  RESULTS Circumferential resection margin negative ( CRM- ) status rate was 68 % in the oxaliplatin group and 70 % in the fluorouracil-only group , p = 0.72 . The pathological complete response rate ( pCR ) was correspondingly 14 % vs. 7 % , p = 0.10 . Following multivariable analysis , when comparing the CRM- status in the oxaliplatin group to the fluorouracil-only group , the odds ratio was 0.79 ( 95 CI 0.35 - 1.74 ) , p = 0.54 ; there being no interaction between concomitant chemoradiation and 5 × 5 Gy with consolidation chemotherapy ; pinteraction = 0.073 . For pCR , the corresponding results were 0.47 ( 95 CI 0.19 - 1.16 ) , p = 0.10 , pinteraction = 0.84 . CONCLUSION No benefit was found of adding oxaliplatin in terms of CRM nor pCR rates for either concomitant or sequential setting s in preoperative radiochemotherapy for very advanced rectal cancer Purpose : To evaluate the efficacy and safety of oxaliplatin ( L-OHP ) in combination with leucovorin (LV)-modulated bolus plus infusional 5-fluorouracil ( 5-FU ; de Gramont schedule ) every 2 weeks in chemotherapy-naive patients with advanced colorectal cancer ( CRC ) . Patients and Methods : Thirty-two patients ( median age : 69 years ) with histologically confirmed and two-dimensionally measurable metastatic CRC were enrolled . The patients ’ performance status ( WHO ) was 0 in 14 ( 44 % ) , 1 in 15 ( 47 % ) , and 2 in 3 ( 9 % ) patients . Twenty ( 62.5 % ) patients had at least two metastatic sites .  LV was administered at a dose of 200 mg/m2/day as a 2-hour intravenous infusion , followed by 5-FU as an intravenous bolus at the dose of 400 mg/m2 and then , as a 22-hour continuous infusion at the dose of 600 mg/m2/day for 2 consecutive days . L-OHP was administered on day 1 at the dose of 85 
    Output:
    
The toxicity  of 5FU + OXA or CAP + OXA was significantly worse than that of 5FU alone or CAP alone .
CAP + OXA and CAP were ranked , respectively , the most and second most effective regimens in terms of pCR rate .
5FU alone and CAP alone likely had the lowest and second lowest toxicity , respectively .
Conclusion Among the currently available CRT regimens for locally advanced rectal cancer , this meta- analysis indicated that CAP + OXA provides the superior clinical results .
Adding OXA to 5FU or CAP significantly increases toxicity