***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 In metastatic colorectal cancer , phase III studies have demonstrated the superiority of fluorouracil ( FU ) with leucovorin ( LV ) in combination with irinotecan or oxaliplatin over FU + LV alone . This phase III study investigated two sequences : folinic acid , FU , and irinotecan ( FOLFIRI ) followed by folinic acid , FU , and oxaliplatin ( FOLFOX6 ; arm A ) , and FOLFOX6 followed by FOLFIRI ( arm B ) . PATIENTS AND METHODS Previously untreated patients with assessable disease were r and omly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2 ) or dl-LV 400 mg/m(2 ) followed by a FU bolus 400 mg/m(2 ) and 46-hour infusion 2,400 to 3,000 mg/m(2 ) every 46 hours every 2 weeks , either with irinotecan 180 mg/m(2 ) or with oxaliplatin 100 mg/m(2 ) as a 2-hour infusion on day 1 . At progression , irinotecan was replaced by oxaliplatin ( arm A ) , or oxaliplatin by irinotecan ( arm B ) . RESULT Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI ( P = .99 ) . Median second progression-free survival ( PFS ) was 14.2 months in arm A versus 10.9 in arm B ( P = .64 ) . In first-line therapy , FOLFIRI achieved 56 % response rate ( RR ) and 8.5 months median PFS , versus FOLFOX6 which achieved 54 % RR and 8.0 months median PFS ( P = .26 ) . Second-line FOLFIRI achieved 4 % RR and 2.5 months median PFS , versus FOLFOX6 which achieved 15 % RR and 4.2 months PFS . In first-line therapy , National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis , nausea/vomiting , and grade 2 alopecia were more frequent with FOLFIRI , and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6 . CONCLUSION Both sequences achieved a prolonged survival and similar efficacy . The toxicity profiles were different PURPOSE In North America , no effective therapy has been available for patients with progressive metastatic colorectal cancer after front-line treatment with irinotecan , bolus fluorouracil ( FU ) , and leucovorin ( IFL ) .  PATIENTS AND METHODS Patients with metastatic colorectal cancer who progressed after IFL therapy  were r and omly assigned to bolus and infusional FU and leucovorin ( LV5FU2 ) , single-agent oxaliplatin , or the combination ( FOLFOX4 ) . This planned interim analysis evaluated objective response rate ( RR ) , time to tumor progression ( TTP ) , and alleviation of tumor-related symptoms ( TRS ) in an initial cohort of patients . RESULTS Between November 2000 and September 2001 , 463 patients from 120 sites in North America were r and omly assigned to treatment . FOLFOX4 proved superior to LV5FU2 in all measures of clinical efficacy . Objective RRs determined by an independent radiology panel were 9.9 % for FOLFOX4 versus 0 % for LV5FU2 ( Fisher 's exact test , P < .0001 ) . Median TTP was 4.6 months for FOLFOX4 versus 2.7 months for LV5FU2 ( two-sided , stratified log-rank test , P < .0001 ) . Relief of TRS occurred in 33 % of patients treated with FOLFOX4 versus 12 % of patients treated with LVFU2 ( chi2 test , P < .001 ) . Single-agent oxaliplatin was not superior to LV5FU2 in any measure of efficacy . Patients treated with FOLFOX4 experienced a higher incidence of clinical ly significant toxicities than patients treated with LV5FU2 , but these toxicities were predictable and did not result in a higher rate of treatment discontinuation or 60-day mortality rate . CONCLUSION For patients with metastatic colorectal cancer , second-line treatment with FOLFOX4 is superior to treatment with LVFU2 in terms of RR , TTP , and relief of TRS PURPOSE We performed this phase III study to compare the irinotecan , leucovorin ( LV ) , and fluorouracil ( FU ) regimen ( FOLFIRI ) versus the oxaliplatin , LV , and FU regimen ( FOLFOX4 ) in previously untreated patients with advanced colorectal cancer . PATIENTS AND METHODS A total of 360 chemotherapy-naive patients were r and omly assigned to receive , every 2 weeks , either arm A ( FOLFIRI : irinotecan 180 mg/m(2 ) on day 1 with LV 100 mg/m(2 ) administered as a 2-hour infusion before FU 400 mg/m(2 ) administered as an intravenous bolus injection , and FU 600 mg/m(2 ) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [ LV5FU2 ] ) or arm B ( FOLFOX4 : oxaliplatin 85 mg/m(2 ) on day 1 with LV5FU2 regimen ) . RESULTS One hundred sixty-four and 172 patients were assessable in arm A and B , respectively . Overall response rates ( ORR ) were 31 % in arm A ( 95 % CI , 24.6 % to 38.3 % ) and 34 % in arm B ( 95 % CI , 27.2 % to 41.5 % ; P = .60 ) . In both arms A and B , median time to progression ( TTP ; 7 v 7 months , respectively ) , duration of response ( 9 v 10 months , respectively ) , and overall survival ( OS ; 14 v 15 months , respectively ) were similar , without any statistically significant difference . Toxicity was mild in both groups : alopecia and gastrointestinal disturbances were the most common toxicities in arm A ; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms , and no statistical significant difference was observed . CONCLUSION There is no difference in ORR , TTP , and OS for patients treated with the FOLFIRI or FOLFOX4 regimen . Both therapies seemed effective as first-line treatment in these patients . The difference between these two combination therapies is mainly in the toxicity profile PURPOSE To determine the activity of biweekly oxaliplatin , combined with weekly bolus fluorouracil ( FU ) and low-dose leucovorin ( LV ) chemotherapy ( bFOL ) , as first-line therapy for patients with metastatic colorectal cancer . PATIENTS AND METHODS Patients with measurable metastatic colorectal cancer ; no previous therapy for advanced disease ( adjuvant therapy allowed if > 6 months since completion ) ; and performance status 0 , 1 , or 2 were eligible and were treated with oxaliplatin 85 mg/m2 days 1 and 15 plus LV 20 mg/m2 over 10 to 20 minutes , followed by a 500 mg/m2 bolus dose of FU on days 1 , 8 , and 15 every 28 days . Patients underwent response evaluation by computed tomographic scan every 2 months . RESULTS Forty-two patients were entered , and 41 patients were treated , including 20 men and 22 women , nine with previous adjuvant chemotherapy and four with radiation therapy .  Three patients achieved complete response , and 23 patients achieved partial response , for a response rate of 63 % ( 95 % CI , 49 % to 78 % ) . Major toxicities included cumulative neuropathy grade 2 ( 24 % ) and grade 3 ( 12 % ; requiring discontinuation of oxaliplatin ) , diarrhea grade 3 to 4 ( 29 % ) and grade 3 to 4 hematologic toxicity ( 10 % ) . Median time to progression was 9.0 months ( 95 % confidence interval , 7.1 to 10.8 months ) with median survival of 15.9 months ( 95 % confidence interval , 11.4 to 19.7 months ) . CONCLUSION The bFOL regimen seems to have activity comparable to be infusional programs of FU combined with oxaliplatin . Prospect i ve trials are warranted to determine the relative merits of this schedule compared with the currently indicated schedules PURPOSE In a previous study of treatment for advanced colorectal cancer , the LV5FU2 regimen , comprising leucovorin ( LV ) plus bolus and infusional fluorouracil ( 5FU ) every 2 weeks , was superior to the st and ard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen . This phase III study investigated the effect of combining oxaliplatin with LV5FU2 , with progression-free survival as the primary end point . PATIENTS AND METHODS Four hundred twenty previously untreated patients with measurable disease were r and omized to receive a 2-hour infusion of LV ( 200 mg/m(2)/d ) followed by a 5FU bolus ( 400 mg/m(2)/d ) and 22-hour infusion ( 600 mg/m(2)/d ) for 2 consecutive days every 2 weeks , either alone or together with oxaliplatin 85 mg/m(2 ) as a 2-hour infusion on day 1 . RESULTS Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival ( median , 9.0 v 6.2 months ; P = .0003 ) and better response rate ( 50.7 % v 22.3 % ; P = .0001 ) when compared with the control arm . The improvement in overall survival did not reach significance ( median , 16.2 v 14.7 months ; P = . 12 ) . LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia ( 41 . 7 % v 5.3 % of patients ) , grade 3/4 diarrhea ( 11.9 % v 5.3 % ) , and grade 3 neurosensory toxicity ( 18.2 % v 0 % ) , but this did not result in impairment of quality of life ( QoL ) . Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment ( P = .004 ) . CONCLUSION The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer , demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of 
    Output:
    
For second-line treatment after fluoropyrimidine monotherapy , folfox is a reasonable alternative for patients with contraindications to second-line irinotecan .
Evidence from a single r and omized trial suggests that additional benefits can be expected with the addition of bevacizumab to the folfox regimen in second-line treatment .
The folfox regimen has superior rates of median survival and tumour response .
Compared with ifl , folfox has lower incidences of severe nausea , vomiting , diarrhea , and febrile neutropenia , but a higher incidence of peripheral neuropathy .
The folfox regimen is a reasonable alternative for patients with contraindications to the use of second-line irinotecan .
After progression on both irinotecan and an anti-thymidylate synthase agent , folfox is the preferred therapy .
Recent trials suggest that , as compared with folfox alone , folfox combined with bevacizumab provides additional survival benefits .