human
***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 European Organisation for Research and Treatment of Cancer ( EORTC ) trial 22921 compared adjuvant fluorouracil-based chemotherapy ( CT ) to no adjuvant treatment in a 2 x 2 factorial trial with r and omization for preoperative (chemo)radiotherapy in patients with resectable T3 - 4 rectal cancer . The results showed no significant impact of adjuvant CT on progression-free or overall survival , although a difference seemed to emerge at approximately , respectively , 2 and 5 years after the start of preoperative treatment . We further explored the data with the aim of refining our underst and ing of the long-term results . PATIENTS AND METHODS Data of 785 of the 1,011 r and omly assigned patients who whose disease was M0 at curative surgery were used . Using meta-analytic methods , we investigated the homogeneity of the effect of adjuvant CT on the time to relapse or death after surgery ( disease-free survival [ DFS ] ) and survival in patient subgroups . RESULTS Although there was no statistically significant impact of adjuvant CT on DFS for the whole group ( P > .5 ) , the treatment effect differed significantly between the ypT0 - 2 and the ypT3 - 4 patients ( heterogeneity P = .009 ) : only the ypT0 - 2 patients seemed to benefit from adjuvant CT ( P = .011 ) . The same pattern was observed for overall survival . CONCLUSION Exploratory analyses suggest that only good-prognosis patients ( ypT0 - 2 ) benefit from adjuvant CT . This could explain why , in the whole group , the progression-free and overall survival diverged only after the poor-prognosis patients ( ypT3 - 4 ) had experienced treatment failure . Patients in whom no downstaging was achieved did not benefit . This also suggests that the same prognostic factors may drive both tumor sensitivity for the primary treatment and long-term clinical benefit from further adjuvant CT The Gastrointestinal Tumor Study Group ( GITSG ) protocol GI-7175 r and omized 227 patients between 1975 and 1980 following complete surgical resection of stages B2 and C rectal adenocarcinoma to four treatment arms : ( 1 ) no adjuvant therapy , ( 2 ) chemotherapy only , ( 3 ) radiotherapy only , and ( 4 ) radiotherapy and chemotherapy ( combined  modality ) . The results of the study showed an advantage for combined modality treatment over no adjuvant therapy for time to recurrence ( p = 0.005 ) and for survival ( p = 0.01 ) . Severe acute toxicity was frequent in the combined modality arm ( 61 % ) but late effects , including radiation enteritis , have been infrequent . We conclude that postoperative adjuvant therapy is indicated in certain stages of rectal carcinoma and that the present state of knowledge suggests combined modality therapy We examined the effects of postoperative 5-fluorouracil ( 5-FU ) infusions and oral treatment with 1-hexylcarbamoyl-5-fluorouracil ( HCFU ) on patients curatively resected for stages II-IV colorectal cancer . The study was prospect ively r and omized , and 251 ( 93.3 % ) of 269 patients were valid c and i date s for statistical assessment . The inductive regimen for group A included 5-FU 10 mg intravenous ( i.v . ) injections on days 0 , 1 , 2 , 7 , 8 and 9 , postoperatively . For maintenance therapy , group A received HCFU 300 mg orally and daily for 52 weeks beginning 2 weeks after surgery . The regimen for group B included only 5-FU injections . The effects of this chemotherapy were also retrospectively analyzed for groups at a high risk for recurrence , stages III-IV , transmural invasion-positive and lymph node metastasis-positive cases . There was no statistical difference in survival time between the groups for 251 eligible cases ( p = 0.079 ) . In group A given 5-FU plus HCFU , there was a reduction in the recurrence rate for patients with stages III-IV or lymph node metastasis-positive colorectal cancers ( p < 0.05 ) and prolongation of the survival time for patients with stage III-IV , transmural invasion-positive or lymph node-positive colorectal cancers ( p < 0.05 ) . Our findings show that the combination of 5-FU infusion and the continuous administration of HCFU is effective in treating patients with surgically resected colorectal cancer who are at high risk for a recurrence A combined intraoperative and postoperative adjuvant program of 5 minus Fluorouracil ( 5 FU ) for patients undergoing " curative " resection for adenocarcinoma of the colon and rectum was initiated as a r and omized clinical trial in January 1968 . Patients at the Medical College of Virginia and the University of Virginia were r and omly assigned to an intraluminal 5 FU or intraluminal control ( Saline ) group and were so treated at the time of surgical resection if findings at operation indicated that all gross neoplastic disease could be resected . Patients with operative findings denoting incurability were eliminated from the study after surgical exploration . Those patients receiving intraluminal 5 FU ( 30mg/kg ) received intravenous 5 FU ( 10mg/kg ) on each of the two first postoperative days and 5 subsequent postoperative courses of oral 5FU ( 90 mg/kg in each 18 day course ) over a one year period . By December 31 , 1973 ( 6 years ) 156 patients undergoing " curative " resection were entered into the study . SU therapy with the control or " No Treat " group reveal no significant benefit from this intensive adjuvant course of 5 FU thus far . Continued assessment of these patient groups and their subgroups will be required to develop confidence in these findings but the data thus far suggest no potential benefit from this particular adjuvant program BACKGROUND The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence , for whom the indication for such treatment is unclear . METHODS After apparently curative resections of colon or rectal cancer , 3239 patients ( 2963 [ 91 % ] with stage II [ node negative ] disease , 2291 [ 71 % ] with colon cancer , median age 63 [ IQR 56 - 68 ] years ) enrolled between May , 1994 , and December , 2003 , from 150 centres in 19 countries were r and omly assigned to receive chemotherapy with fluorouracil and folinic acid ( n=1622 ) or to observation ( with chemotherapy considered on recurrence ; n=1617 ) . Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil ( 370 mg/m2 ) with high-dose ( 175 mg ) L-folinic acid or low-dose ( 25 mg ) L-folinic acid . Until 1997 , levamisole ( 12 courses of 450 mg over 3 days repeated every 2 weeks ) or placebo was added . After 1997 , patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only . The primary outcome was all-cause mortality . Analyses were done by intention to treat . This trial is registered with the International Clinical Trial Registry , number IS RCT N82375386 . FINDINGS At the time of analysis , 61 ( 3.8 % ) patients in the chemotherapy group and 50 ( 3.1 % ) in the observation group had missing follow-up . After a median follow-up of 5.5 ( range 0 - 10.6 ) years , there were 311 deaths in the chemotherapy group and 370 in the observation group ; the relative risk of death from any cause with chemotherapy versus observation alone was 0.82 ( 95 % CI 0.70 - 0.95 ; p=0.008 ) . There were 293 recurrences in the chemotherapy group and 359 in the observation group ; the relative risk of recurrence with chemotherapy versus observation alone was 0.78 ( 0.67 - 0.91 ; p=0.001 ) . Treatment efficacy did not differ significantly by tumour site , stage , sex , age , or chemotherapy schedule . Eight ( 0.5 % ) patients in the chemotherapy group and four ( 0.25 % ) in the observation group died from non-colorectal cancer causes within 30 weeks of r and omisation ; only one of these deaths was deemed to be possibly chemotherapy related . INTERPRETATION Chemotherapy with fluorouracil and folinic acid could improve survival of patients with stage II colorectal cancer , although the absolute improvements are small : assuming 5-year mortality without chemotherapy is 20 % , the relative risk of death seen here translates into an absolute improvement in survival of 3.6 % ( 95 % CI 1.0 - 6.0 ) Objective In the latter 1990s , adjuvant chemotherapy for completely resected Stage III colorectal cancer remained controversial in Japan . We conducted two independent r and omized controlled trials in patients with Stage III colon and rectal cancer . Methods Patients were r and omly assigned to receive surgery alone or surgery followed by treatment with UFT ( 400 mg/m2/day ) , given for five consecutive days per week for 1 year . The primary endpoint was relapse-free survival ( RFS ) , and the secondary endpoint was overall survival ( OS ) . Results A total of 334 patients with colon cancer and 276 with rectal cancer were enrolled . The patients ’ characteristics were similar between the UFT group and the Surgery-alone group . There was no significant difference in RFS or OS in colon cancer . In rectal cancer , however , RFS and OS were significantly better in the UFT group than in the Surgery-alone group . The only grade 4 toxicity in the UFT group was diarrhea , occurring in one patient with colon cancer and one patient with rectal cancer . Conclusions Postoperative adjuvant chemotherapy with UFT is successfully tolerated and improves RFS and OS in patients with Stage III rectal cancer . In colon cancer , the expected benefits were not obtained ( hazard ratio = 0.89 ) BACKGROUND R and omized studies have shown that postoperative chemotherapy with or without radiation therapy ( RT ) improved local control and survival of patients with stages II or III rectal cancer . However , the optimal sequence of treatments and the optimal chemotherapeutic regimen have not been defined . Modulation of fluorouracil ( FU ) by leucovorin ( LV ) has yielded a highly significant difference in response rate from that of FU monotherapy , as suggested by an overview of r and omized trials in patients with advanced colorectal cancer . However , this difference in response rate did not translate into a survival benefit . PURPOSE To evaluate the impact on the disease-free survival ( DFS ) and overall survival ( OS ) of patients with stages II or III rectal cancer of postoperative RT and concomitant bolus FU  administration alone or with additional chemotherapy using FU and high-dose LV . PATIENTS AND METHODS From October 1989 until February 1997 , 220 patients were r and omized postoperatively to receive either one cycle of chemotherapy with FU ( 600 mg/m2/week x 6 followed by a two-week rest ) and leucovorin ( LV , 500 mg/m2/week x 6 as a two-hour infusion ) followed by pelvic RT with concomitant FU ( 400 mg/m2 ) as a rapid intravenous injection during the first three and last three days of RT , and three more cycles of the same chemotherapy with FU and LV ( st and ard , group A , 111 patients ) or pelvic RT with concomitant FU only ( experimental , group B , 109 patients ) . RESULTS As of August 1998 , after a median follow-up of 4.9 years , there was no significant difference in either three-year DFS ( Group A , 70.3 % ; group B , 68.2 % , P = 0.53 ) or OS ( group A , 77 % ; group B , 73.3 % . P = 0.75 ) . Cox multivariate analysis revealed stage of disease , number of infiltrated nodes , tumor grade , presence of regional implants and perforation to be significant prognostic factors . The incidence of severe side effects was significantly higher in the patients in group A than in those in group B ( 32.4 % vs. 4.6 % , P < 0.0001 ) . CONCLUSIONS The incorporation of additional chemotherapy with FU and LV into postoperative concomitant RT and bolus infusion of FU does not offer a > or = 10 % three-year survival benefit over that of concomitant RT and bolus infusion of FU , and significantly increases toxicity in patients with stages II or III rectal cancer Background : The purpose of this study is to evaluate the efficacy of postoperative adjuvant chemotherapy using uracil and tegafur ( UFT ) for colorectal cancer . Methods : In a multicenter trial among 43 institutions for patients who underwent curative resection of Dukes ’ B or C colorectal cancer , a  surgery alone group ( control group ) and a treatment group ( UFT group ) to which UFT was administered at 400 m 
    Output:
    
agent
***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 European Organisation for Research and Treatment of Cancer ( EORTC ) trial 22921 compared adjuvant fluorouracil-based chemotherapy ( CT ) to no adjuvant treatment in a 2 x 2 factorial trial with r and omization for preoperative (chemo)radiotherapy in patients with resectable T3 - 4 rectal cancer . The results showed no significant impact of adjuvant CT on progression-free or overall survival , although a difference seemed to emerge at approximately , respectively , 2 and 5 years after the start of preoperative treatment . We further explored the data with the aim of refining our underst and ing of the long-term results . PATIENTS AND METHODS Data of 785 of the 1,011 r and omly assigned patients who whose disease was M0 at curative surgery were used . Using meta-analytic methods , we investigated the homogeneity of the effect of adjuvant CT on the time to relapse or death after surgery ( disease-free survival [ DFS ] ) and survival in patient subgroups . RESULTS Although there was no statistically significant impact of adjuvant CT on DFS for the whole group ( P > .5 ) , the treatment effect differed significantly between the ypT0 - 2 and the ypT3 - 4 patients ( heterogeneity P = .009 ) : only the ypT0 - 2 patients seemed to benefit from adjuvant CT ( P = .011 ) . The same pattern was observed for overall survival . CONCLUSION Exploratory analyses suggest that only good-prognosis patients ( ypT0 - 2 ) benefit from adjuvant CT . This could explain why , in the whole group , the progression-free and overall survival diverged only after the poor-prognosis patients ( ypT3 - 4 ) had experienced treatment failure . Patients in whom no downstaging was achieved did not benefit . This also suggests that the same prognostic factors may drive both tumor sensitivity for the primary treatment and long-term clinical benefit from further adjuvant CT The Gastrointestinal Tumor Study Group ( GITSG ) protocol GI-7175 r and omized 227 patients between 1975 and 1980 following complete surgical resection of stages B2 and C rectal adenocarcinoma to four treatment arms : ( 1 ) no adjuvant therapy , ( 2 ) chemotherapy only , ( 3 ) radiotherapy only , and ( 4 ) radiotherapy and chemotherapy ( combined  modality ) . The results of the study showed an advantage for combined modality treatment over no adjuvant therapy for time to recurrence ( p = 0.005 ) and for survival ( p = 0.01 ) . Severe acute toxicity was frequent in the combined modality arm ( 61 % ) but late effects , including radiation enteritis , have been infrequent . We conclude that postoperative adjuvant therapy is indicated in certain stages of rectal carcinoma and that the present state of knowledge suggests combined modality therapy We examined the effects of postoperative 5-fluorouracil ( 5-FU ) infusions and oral treatment with 1-hexylcarbamoyl-5-fluorouracil ( HCFU ) on patients curatively resected for stages II-IV colorectal cancer . The study was prospect ively r and omized , and 251 ( 93.3 % ) of 269 patients were valid c and i date s for statistical assessment . The inductive regimen for group A included 5-FU 10 mg intravenous ( i.v . ) injections on days 0 , 1 , 2 , 7 , 8 and 9 , postoperatively . For maintenance therapy , group A received HCFU 300 mg orally and daily for 52 weeks beginning 2 weeks after surgery . The regimen for group B included only 5-FU injections . The effects of this chemotherapy were also retrospectively analyzed for groups at a high risk for recurrence , stages III-IV , transmural invasion-positive and lymph node metastasis-positive cases . There was no statistical difference in survival time between the groups for 251 eligible cases ( p = 0.079 ) . In group A given 5-FU plus HCFU , there was a reduction in the recurrence rate for patients with stages III-IV or lymph node metastasis-positive colorectal cancers ( p < 0.05 ) and prolongation of the survival time for patients with stage III-IV , transmural invasion-positive or lymph node-positive colorectal cancers ( p < 0.05 ) . Our findings show that the combination of 5-FU infusion and the continuous administration of HCFU is effective in treating patients with surgically resected colorectal cancer who are at high risk for a recurrence A combined intraoperative and postoperative adjuvant program of 5 minus Fluorouracil ( 5 FU ) for patients undergoing " curative " resection for adenocarcinoma of the colon and rectum was initiated as a r and omized clinical trial in January 1968 . Patients at the Medical College of Virginia and the University of Virginia were r and omly assigned to an intraluminal 5 FU or intraluminal control ( Saline ) group and were so treated at the time of surgical resection if findings at operation indicated that all gross neoplastic disease could be resected . Patients with operative findings denoting incurability were eliminated from the study after surgical exploration . Those patients receiving intraluminal 5 FU ( 30mg/kg ) received intravenous 5 FU ( 10mg/kg ) on each of the two first postoperative days and 5 subsequent postoperative courses of oral 5FU ( 90 mg/kg in each 18 day course ) over a one year period . By December 31 , 1973 ( 6 years ) 156 patients undergoing " curative " resection were entered into the study . SU therapy with the control or " No Treat " group reveal no significant benefit from this intensive adjuvant course of 5 FU thus far . Continued assessment of these patient groups and their subgroups will be required to develop confidence in these findings but the data thus far suggest no potential benefit from this particular adjuvant program BACKGROUND The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence , for whom the indication for such treatment is unclear . METHODS After apparently curative resections of colon or rectal cancer , 3239 patients ( 2963 [ 91 % ] with stage II [ node negative ] disease , 2291 [ 71 % ] with colon cancer , median age 63 [ IQR 56 - 68 ] years ) enrolled between May , 1994 , and December , 2003 , from 150 centres in 19 countries were r and omly assigned to receive chemotherapy with fluorouracil and folinic acid ( n=1622 ) or to observation ( with chemotherapy considered on recurrence ; n=1617 ) . Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil ( 370 mg/m2 ) with high-dose ( 175 mg ) L-folinic acid or low-dose ( 25 mg ) L-folinic acid . Until 1997 , levamisole ( 12 courses of 450 mg over 3 days repeated every 2 weeks ) or placebo was added . After 1997 , patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only . The primary outcome was all-cause mortality . Analyses were done by intention to treat . This trial is registered with the International Clinical Trial Registry , number IS RCT N82375386 . FINDINGS At the time of analysis , 61 ( 3.8 % ) patients in the chemotherapy group and 50 ( 3.1 % ) in the observation group had missing follow-up . After a median follow-up of 5.5 ( range 0 - 10.6 ) years , there were 311 deaths in the chemotherapy group and 370 in the observation group ; the relative risk of death from any cause with chemotherapy versus observation alone was 0.82 ( 95 % CI 0.70 - 0.95 ; p=0.008 ) . There were 293 recurrences in the chemotherapy group and 359 in the observation group ; the relative risk of recurrence with chemotherapy versus observation alone was 0.78 ( 0.67 - 0.91 ; p=0.001 ) . Treatment efficacy did not differ significantly by tumour site , stage , sex , age , or chemotherapy schedule . Eight ( 0.5 % ) patients in the chemotherapy group and four ( 0.25 % ) in the observation group died from non-colorectal cancer causes within 30 weeks of r and omisation ; only one of these deaths was deemed to be possibly chemotherapy related . INTERPRETATION Chemotherapy with fluorouracil and folinic acid could improve survival of patients with stage II colorectal cancer , although the absolute improvements are small : assuming 5-year mortality without chemotherapy is 20 % , the relative risk of death seen here translates into an absolute improvement in survival of 3.6 % ( 95 % CI 1.0 - 6.0 ) Objective In the latter 1990s , adjuvant chemotherapy for completely resected Stage III colorectal cancer remained controversial in Japan . We conducted two independent r and omized controlled trials in patients with Stage III colon and rectal cancer . Methods Patients were r and omly assigned to receive surgery alone or surgery followed by treatment with UFT ( 400 mg/m2/day ) , given for five consecutive days per week for 1 year . The primary endpoint was relapse-free survival ( RFS ) , and the secondary endpoint was overall survival ( OS ) . Results A total of 334 patients with colon cancer and 276 with rectal cancer were enrolled . The patients ’ characteristics were similar between the UFT group and the Surgery-alone group . There was no significant difference in RFS or OS in colon cancer . In rectal cancer , however , RFS and OS were significantly better in the UFT group than in the Surgery-alone group . The only grade 4 toxicity in the UFT group was diarrhea , occurring in one patient with colon cancer and one patient with rectal cancer . Conclusions Postoperative adjuvant chemotherapy with UFT is successfully tolerated and improves RFS and OS in patients with Stage III rectal cancer . In colon cancer , the expected benefits were not obtained ( hazard ratio = 0.89 ) BACKGROUND R and omized studies have shown that postoperative chemotherapy with or without radiation therapy ( RT ) improved local control and survival of patients with stages II or III rectal cancer . However , the optimal sequence of treatments and the optimal chemotherapeutic regimen have not been defined . Modulation of fluorouracil ( FU ) by leucovorin ( LV ) has yielded a highly significant difference in response rate from that of FU monotherapy , as suggested by an overview of r and omized trials in patients with advanced colorectal cancer . However , this difference in response rate did not translate into a survival benefit . PURPOSE To evaluate the impact on the disease-free survival ( DFS ) and overall survival ( OS ) of patients with stages II or III rectal cancer of postoperative RT and concomitant bolus FU  administration alone or with additional chemotherapy using FU and high-dose LV . PATIENTS AND METHODS From October 1989 until February 1997 , 220 patients were r and omized postoperatively to receive either one cycle of chemotherapy with FU ( 600 mg/m2/week x 6 followed by a two-week rest ) and leucovorin ( LV , 500 mg/m2/week x 6 as a two-hour infusion ) followed by pelvic RT with concomitant FU ( 400 mg/m2 ) as a rapid intravenous injection during the first three and last three days of RT , and three more cycles of the same chemotherapy with FU and LV ( st and ard , group A , 111 patients ) or pelvic RT with concomitant FU only ( experimental , group B , 109 patients ) . RESULTS As of August 1998 , after a median follow-up of 4.9 years , there was no significant difference in either three-year DFS ( Group A , 70.3 % ; group B , 68.2 % , P = 0.53 ) or OS ( group A , 77 % ; group B , 73.3 % . P = 0.75 ) . Cox multivariate analysis revealed stage of disease , number of infiltrated nodes , tumor grade , presence of regional implants and perforation to be significant prognostic factors . The incidence of severe side effects was significantly higher in the patients in group A than in those in group B ( 32.4 % vs. 4.6 % , P < 0.0001 ) . CONCLUSIONS The incorporation of additional chemotherapy with FU and LV into postoperative concomitant RT and bolus infusion of FU does not offer a > or = 10 % three-year survival benefit over that of concomitant RT and bolus infusion of FU , and significantly increases toxicity in patients with stages II or III rectal cancer Background : The purpose of this study is to evaluate the efficacy of postoperative adjuvant chemotherapy using uracil and tegafur ( UFT ) for colorectal cancer . Methods : In a multicenter trial among 43 institutions for patients who underwent curative resection of Dukes ’ B or C colorectal cancer , a  surgery alone group ( control group ) and a treatment group ( UFT group ) to which UFT was administered at 400 m 
    Output:
    