***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 The aim of this r and omised trial was to evaluate the activity and toxicity of a biweekly regimen including 6S-leucovorin-modulated 5-fluorouracil ( LFA-5-FU ) , combined with either irinotecan ( CPT-11 + LFA 5-FU ) or raltitrexed ( Tomudex ) ( TOM + LFA-5-FU ) , in advanced colorectal cancer patients , and to make a preliminary comparison of both these experimental regimens with a biweekly administration of LFA-5-FU modulated by methotrexate ( MTX + LFA-5-FU ) . PATIENTS AND METHODS One hundred fifty-nine patients with advanced colorectal carcinoma previously untreated for the metastatic disease ( 34 of them previously exposed to adjuvant 5-FU ) were r and omly allocated to receive : CPT-11 , 200 mg/m2 i.v . on day 1 , followed on day 2 by LFA , 250 mg/m2 i.v . infusion and 5-FU , 850 mg/m2 s i.v . bolus ( arm A ) ; TOM , 3 mg/m2 i.v . on day 1 , followed on day 2 by LFA , 250 mg/m2 i.v . infusion and 5-FU , 1050 mg/m2 i.v . bolus ( arm B ) ; or MTX , 750 mg/m2 i.v . on day 1 , followed on day 2 by LFA , 250 mg/m2 i.v . infusion and 5-FU , 800 mg/m2 i.v . bolus ( arm C ) . Courses were repeated every two weeks in all arms of the trial . Response rate ( RR ) was evaluated after every four courses . The sample size was defined to have an 80 % power to detect a 35 % RR for each experimental treatment , and to show a difference of at least 4 % in RR with the st and ard treatment if the true difference is 15 % or more . RESULTS The RRs were : 34 % ( 95 % confidence interval ( 95 % , CI ) : 21%-48 % ) in arm A , including 3 complete responses ( CRs ) and 15 partial responses ( PRs ) , 24 % ( 95 % CI : 14%-38 % ) in arm B , including 2 CRs and 11 PRs , and 24 % ( 95 % CI : 14%-38 % ) , with 2 CRs and 11 PRs , in arm C. After a median follow-up time of 62 ( range 18 - 108 ) weeks , the median time to progression was 38 , 25 , and 27 weeks for arm A , B , and C , respectively . With 94 patients still alive , the one-year probability of survival was 61 % , 54 % , and 59 % , respectively . WHO grade 3 or 4 neutropenia and diarrhoea affected 46 % and 16 % , respectively , of patients treated with CPT-11 + LFA 5-FU .  Median relative dose intensity over eight cycles ( DI8 ) was 78 % for CPT-11 and 82 % for 5-FU .  Severe toxicities of TOM + LFA-5-FU were neutropenia ( 16 % ) and diarrhoea ( 16 % ) , but median relative DI8 was 93 % for TOM , and 82 % for 5-FU . CONCLUSIONS CPT-11 + LFA-5-FU compares favorably in term of activity and toxicity with other combination regimens including CPT-11 and continuous infusional 5-FU . The hypothesis of a RR 15 % higher than the MTX + LFA-5-FU treatment can not be ruled out after this interim analysis . The TOM + LFA 5-FU regimen showed a RR and a toxicity profile very close to the MTX + LFA 5-FU combination , and dose not deserve further evaluation in advanced colorectal cancer patients Elderly patients are recommended to have a reduced starting dose ( 300 mg m−2 once every 3 weeks ) of irinotecan monotherapy . The aims of this analysis are to compare toxicity and survival according to age , performance status ( PS ) , gender and prior radical pelvic radiotherapy ( RT ) . The primary end points were overall survival and an irinotecan-specific toxicity composite end point ( TCE ) defined as the occurrence of grade 3 or 4 diarrhoea , neutropenia , febrile neutropenia , fever , infection or nausea and vomiting .  Between 1997 and 2003 , 339 eligible patients with advanced colorectal cancer ( CRC ) progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospect ively registered in a multicentre r and omised trial . All patients commenced irinotecan at 350 mg m−2 once every 3 weeks . There were no differences in proportions of patients developing TCE by age ( < 70 vs ⩾70 : 37.8 vs 45.8 % ; P=0.218 ) , PS ( 0–1 vs 2 : 39.3 vs 41.5 % ; P=0.793 ) or prior RT ( RT vs no RT : 45.1 vs 38.5 % ; P=0.377 ) . Males experienced more toxicity than females ( 44.3 vs 32.6 % ; P=0.031 ) , but this was not significant after controlling for other co-variates ( P=0.06 ) . Patients aged ⩾70 had similar objective responses ( 11.1 vs 9 % ; P=0.585 ) and survival ( median 9.4 vs 9 months ; log rank P=0.74 ) compared to younger patients . Elderly patients derive the same benefit without experiencing more toxicity  with second-line irinotecan treatment for advanced CRC . Our data do not support the recommendation to reduce the starting dose for the elderly patients PURPOSE Irinotecan given until disease progression is an accepted st and ard treatment for advanced colorectal cancer ( CRC ) resistant to fluoropyrimidines . It is not known whether a predefined period of irinotecan treatment would result in similar duration of disease control . We performed a multicenter phase III trial to compare the two policies of defined- duration versus continuous irinotecan treatment . PATIENTS AND METHODS Three hundred thirty-three eligible patients with advanced CRC progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospect ively registered . After receiving eight cycles of irinotecan given at 350 mg/m2 once every 3 weeks , 55 patients with responding or stable disease were r and omly assigned to stop irinotecan ( n = 30 ) or continue until disease progression ( n = 25 ) . Registered patients were not r and omly assigned predominantly due to disease progression ( n = 236 ) and intolerable toxicity ( n = 38 ) . RESULTS From the time of r and om assignment , there were no differences in failure-free survival ( P = .999 ) or overall survival ( P = .11 ) between the two arms . No difference was seen in mean global health status quality -of-life score between the two arms at 12 weeks after r and om assignment . No grade 3 diarrhea and febrile neutropenia was seen in the continue-irinotecan arm after r and om assignment . CONCLUSION For most patients , the decision to continue on irinotecan beyond 24 weeks is influenced by disease progression or treatment-related toxicity . However , for 17 % of patients in whom this decision is clinical ly relevant , there seems to be little benefit from continuing irinotecan , though the drug was well tolerated without any deterioration in quality of life 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 To determine whether R115777 improves survival in patients with refractory advanced colorectal cancer ( CRC ) in a multicenter , double-blind , prospect i ve r and omized study . PATIENTS AND METHODS Three hundred sixty-eight patients were r and omly assigned to R115777 ( 300 mg twice daily ) orally for 21 days every 28 days or placebo in a 2:1 ratio . All patients received best supportive care . The primary end point was overall survival ; secondary end points were progression free survival , tumor response , toxicity , and quality of life . RESULTS The two treatment groups were well balanced for baseline demographics , including previous chemotherapy for advanced CRC . The median overall survival for R115777 was 174 days ( 95 % CI , 157 to 198 days ) , and 185 days ( 95 % CI , 158 to 238 days ) for those patients receiving placebo ( P = .376 ) . One patient achieved a partial response in the R115777 arm . Stable disease ( > 3 months ) was observed in 24.3 % patients in the R115777 group compared to 12.8 % in the placebo arm . This did not translate into a statistically significant increase in progression-free survival . Overall , treatment was well tolerated . There was an increased incidence of reversible myelosuppression ( neutropenia , thrombocytopenia ) , rash , and grade 1 to 2 diarrhea in the R115777 arm . There was no statistically significant difference in quality of life between arms . CONCLUSION Single agent R115777 , given at this dose and schedule , has an acceptable toxicity profile , but does not improve overall survival compared to best supportive care alone in refractory advanced CRC PURPOSE In the OPTIMOX1 trial , previously untreated patients with advanced colorectal cancer were r and omly assigned to two different schedules of leucovorin , fluorouracil , and oxaliplatin that were administered until progression in the control arm or in a stop- and -go fashion in the experimental arm . The r and omly assigned treatment groups did not differ significantly in terms of response rate , progression-free survival , and overall survival ( OS ) . However , the impact of oxaliplatin re introduction on OS was potentially masked by the fact that a large number of patients did not receive the planned oxaliplatin re introduction or received oxaliplatin after second-line therapy in both treatment groups . PATIENTS AND METHODS A Cox model was fitted with all significant baseline factors plus time-dependent variables reflecting tumor progression , re introduction of oxaliplatin , and use of second-line irinotecan . A shared frailty model was fitted with all significant baseline factors plus the number of lines of chemotherapy received by the patient and the percentage of patients with oxaliplatin re introduction in the center . An adjusted hazard ratio ( HR ) was calculated for three re introduction classes ( 1 % to 20 % , 21 % to 40 % , and > 40 % ) , using centers with no re introduction ( 0 % ) as the reference group . RESULTS Oxaliplatin re introduction had an independent and significant impact on OS ( HR = 0.56 , P = .009 ) . The percentage of patients with oxaliplatin re introduction s also had a significant impact on OS . Centers in which more than 40 % of the patients were reintroduced had an adjusted HR for OS of 0.59 compared with centers in which no patient was reintroduced . CONCLUSION Oxaliplatin re introduction is associated with improved survival in patients with advanced colorectal cancer Purpose To 
    Output:
    
Second-line chemotherapy ( irinotecan ) showed moderate benefits in overall survival and progression-free survival over Best Supportive Care ( BSC ) and fluorouracil ( 5-FU ) .
Fractionated administration has not proven to be more beneficial and is more toxic .
Second-line chemotherapy is effective in prolonging time to progression and survival in patients with advanced colorectal cancer .