Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience. Postoperative adjuvant chemotherapy with 1-hexylcarbamoyl-5-fluorouracil in patients with colorectal cancer and at a high risk for recurrence. Chemotherapy as an Adjuvant to Surgery for Colorectal Cancer Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC) Postoperative radiation and concomitant bolus fluorouracil with or without additional chemotherapy with fluorouracil and high-dose leucovorin in patients with high-risk rectal cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer: multicenter prospective randomized trial Randomised clinical trial of adjuvant postoperative RT vs. sequential postoperative RT plus 5-FU and levamisole in patients with stage II-III resectable rectal cancer: a final report. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. The diagnosis and management of rectal cancer: expert discussion and recommendations derived from the 9th World Congress on Gastrointestinal Cancer, Barcelona, 2007. 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Impact of the introduction and training of total mesorectal excision on recurrence and survival in rectal cancer in The Netherlands Neoadjuvant Capecitabine Combined with Standard Radiotherapy in Patients with Locally Advanced Rectal Cancer Adjuvant chemotherapy in cancer of the colon and rectum: demonstration of effectiveness of prolonged 5-FU chemotherapy in a prospectively controlled, randomized trial. A Prospective Randomized Trial Comparing Intravenous 5- Fluorouracil and Oral Doxifluridine As Postoperative Adjuvant Treatment for Advanced Rectal Cancer Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012. Effective surgical adjuvant therapy for high-risk rectal carcinoma. Oral adjuvant chemotherapy with carmofur (HCFU) for colorectal cancer: five-year follow-up. Tokai HCFU Study Group--third study on colorectal cancer. Chemotherapy as an adjuvant to surgery for colorectal cancer. A follow-up report. Surgical adjuvant therapy of rectal carcinoma: a controlled evaluation of leucovorin, 5-fluorouracil and radiation therapy with or without interferon-alpha2b. Adjuvant therapy in colorectal cancer. (A randomized trial comparing radio-chemotherapy and radio-chemotherapy combined with the methanol extraction residue of BCG, MER). Results of postoperative treatment of colorectal cancer by radiotherapy, chemotherapy and immunotherapy. Chemotherapy with preoperative radiotherapy in rectal cancer. Improved Overall Survival Among Responders to Preoperative Chemoradiation for Locally Advanced Rectal Cancer Randomized, controlled study of continuous 5-FU infusion starting immediately after curative surgery for advanced colorectal cancer. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. Postoperative Chemotherapy May Not Be Necessary for Patients With ypN0-Category After Neoadjuvant Chemoradiotherapy of Rectal Cancer Adjuvant chemotherapy with uracil-tegafur for pathological stage III rectal cancer after mesorectal excision with selective lateral pelvic lymphadenectomy: a multicenter randomized controlled trial. Importance of 5-fluorouracil dose-intensity in a double randomised trial on adjuvant portal and systemic chemotherapy for Dukes B2 and C colorectal cancer. Improved survival with preoperative radiotherapy in resectable rectal cancer. Preoperative concurrent radiotherapy with capecitabine before total mesorectal excision in locally advanced rectal cancer.
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 mg/day for 2 years following surgery were compared . A total of 320 patients were registered between March 1991 and April 1994 , and 289 of these patients were analyzed as a full- analysis set . Results : The 5-year disease-free survival rate was 75.7 % in the UFT group and 60.1 % in the control group , respectively , and the stratified log-rank test showed the statistical significance ( P=0.0081 ) . This difference was marked in rectal cancer ( P=0.0016 ) and , in particular , the local recurrence was reduced . No significant difference was observed in the 5-year survival rate . The incidence of adverse reactions on administration of UFT was low , and there was no serious adverse reaction . Conclusion : It is suggested that the consecutive administration of UFT at 400 mg/day was an effective and highly safe therapeutic method as postoperative adjuvant chemotherapy for rectal cancer BACKGROUND AND OBJECTIVES A r and omised clinical trial was performed in patients undergoing radical surgery for rectal cancer to compare the efficacy and toxicity of adjuvant postoperative radiation therapy ( RT ) to sequential RT and chemotherapy ( CT ) with 5-fluorouracil ( 5-FU ) plus levamisole ( LEV ) . The primary end point was overall survival ( OS ) ; secondary end points were disease-free survival ( DFS ) , the rate of loco-regional recurrence , and treatment-related toxicity ; the final results of this trial are reported . METHODS Patients in arm I underwent RT ( 50 Gy ) in daily fractions of 2 Gy , 5 days/week for 5 weeks . Patients in arm II began with 5-FU ( 450 mg/sqm/day intravenous ( i.v . ) bolus , days 1 - 5 ) plus LEV ( 150 mg/day orally , days 1 - 3 ) ; postoperative RT was delivered during week 2 at the same dosage and schedule as in arm I. The other five cycles of CT ( 5-FU every 28 days and LEV every 15 days for the length of 5-FU administration ) continued after the end of RT if clinical and hemato-biochemical parameters were in the normal range . RESULTS From May 1992 to December 1998 , 218 patients were enrolled into the r and omised clinical trial ( 144 men , 74 women ; age range : 28 - 75 , median 64 years ) . The median follow-up time was 58.1 months ( range : 1 - 3,271 days ) . No significant difference was observed between the two arms of treatment as regards OS and DFS ( P = 0.18 and P = 0.66 , respectively ) . Cox regression analysis for OS confirmed what was observed by univariate analysis for all variables except age . Older age ( > 60 years ) and pathologic lymph-node involvement defined the subgroups with the worst prognosis . Cox regression analysis for DFS confirmed what was observed by univariate analysis for all variables : the only independent variable in predicting DFS was pathologic lymph-node involvement . CONCLUSIONS Our findings suggest no difference in OS , loco-regional and distant site progressions of postoperative RT alone compared to sequential postoperative RT and CT ; notably , this latter regimen was associated with higher toxicity which seriously impaired the patient 's compliance to CT . The low loco-regional recurrence rate ( 9.2 % ) observed in our patients undergoing postoperative RT alone compared to similarly treated patients in previously performed clinical trials ( 20 - 25 % ) underline the role of radical surgery ( mesorectal excision ) coupled with a complete postoperative RT regimen . On the other h and , the similar efficacy of these two adjuvant modalities of treatment might be conditioned by both the low compliance ( 59 % ) to the CT regimen as well as the sequential , instead of concurrent , schedule of administration of RT and CT , which may have decreased further the expected efficacy of the combined regimen BACKGROUND The combination of radiation therapy and chemotherapy with fluorouracil plus semustine after surgery has been established as an effective approach to decreasing the risk of tumor relapse and improving survival in patients with rectal cancer who are at high risk for relapse or death . We sought to determine whether the efficacy of chemotherapy could be improved by administering fluorouracil by protracted infusion throughout the duration of radiation therapy and whether the omission of semustine would reduce the toxicity and delayed complications of chemotherapy without decreasing its antitumor efficacy . METHODS Six hundred sixty patients with TNM stage II or III rectal cancer received intermittent bolus injections or protracted venous infusions of fluorouracil during postoperative radiation to the pelvis . They also received systemic chemotherapy with semustine plus fluorouracil or with fluorouracil alone in a higher dose , administered before and after the pelvic irradiation . RESULTS With a median follow-up of 46 months among surviving patients , patients who received a protracted infusion of fluorouracil had a significantly increased time to relapse ( P = 0.01 ) and improved survival ( P = 0.005 ) . There was no evidence of a beneficial effect in the patients who received semustine plus fluorouracil . CONCLUSIONS A protracted infusion of fluorouracil during pelvic irradiation improved the effect of combined-treatment postoperative adjuvant therapy in patients with high-risk rectal cancer .  Semustine plus fluorouracil was not more effective than a higher dose of systemic fluorouracil given alone Knowledge of the biology and management of rectal cancer continues to improve . A multidisciplinary approach to a patient with rectal cancer by an experienced expert team is m and atory , to assure optimal diagnosis and staging , surgery , selection of the appropriate neo-adjuvant and adjuvant strategy and chemotherapeutic management . Moreover , optimal symptom management also requires a dedicated team of health care professionals . The introduction of total mesorectal excision has been associated with a decrease in the rate of local failure after surgery . High quality surgery and the achievement of pathological measures of quality are a prerequisite to adequate locoregional control . There are now r and omized data in favour of chemoradiotherapy or short course radiotherapy in the preoperative setting . Preoperative chemoradiotherapy is more beneficial and has less toxicity for patients with resectable rectal cancer than postoperative chemoradiotherapy . Furthermore chemoradiotherapy leads also to downsizing of locally advanced rectal cancer . New strategies that decrease the likelihood of distant metastases after initial treatment need be developed with high priority . Those involved in the care for patients with rectal cancer should be encouraged to participate in well- design ed clinical trials , to increase the evidence -based knowledge and to make further progress . Health care workers involved in the care of rectal cancer patients should be encouraged to adopt quality control processes leading to increased expertise BACKGROUND Postoperative chemoradiotherapy is the recommended st and ard therapy for patients with locally advanced rectal cancer . In recent years , encouraging results with preoperative radiotherapy have been reported . We compared preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally advanced rectal cancer . METHODS We r and omly assigned patients with clinical stage T3 or T4 or node-positive disease to receive either  preoperative or postoperative chemoradiotherapy . The preoperative treatment consisted of 5040 cGy delivered in fractions of 180 cGy per day , five days per week , and fluorouracil , given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per square meter of body-surface area per day during the first and fifth weeks of radiotherapy . Surgery was performed six weeks after the completion of chemoradiotherapy . One month after surgery , four five-day cycles of fluorouracil ( 500 mg per square meter per day ) were given . Chemoradiotherapy was identical in the postoperative-treatment group , except for the delivery of a boost of 540 cGy . The primary end point was overall survival . RESULTS Four hundred twenty-one patients were r and omly assigned to receive preoperative chemoradiotherapy  and 402 patients to receive postoperative chemoradiotherapy . The overall five-year survival rates were 76 percent and 74 percent , respectively ( P=0.80 ) . The five-year cumulative incidence of local relapse was 6 percent for patients assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-treatment group ( P=0.006 ) . Grade 3 or 4 acute toxic effects occurred in 27 percent of the patients in the preoperative-treatment group , as compared with 40 percent of the patients in the postoperative-treatment group ( P=0.001 ) ; the corresponding rates of long-term toxic effects were 14 percent and 24 percent , respectively ( P=0.01 ) . CONCLUSIONS Preoperative chemoradiotherapy , as compared with postoperative chemoradiotherapy , improved local control and was associated with reduced toxicity but did not improve overall survival Based on the first favourable results of adjuvant therapy of 5FU plus levamisole in Dukes C colonic cancer in 1990 , we conducted a prospect i ve trial . 1029 patients were r and omised to receive one year 5FU plus levamisole or no further treatment following curative surgery for stage II or III colon ( n = 730 ) or rectal cancer ( n = 299 ) . 45 % were in stage II and 55 % in stage III . With a median follow-up of 4 years and 9 months a significant reduction in odds of death ( 25 % , SD 9 % , P = 0.007 ) was observed for those with adjuvant treatment ( 65 % at 5 year ) compared to the observation group ( 55 % ) . Improved relative survival was present in stage III ( 56 % vs 44 % ) , and in stage II patients ( 78 % vs 70 % ) . In rectal cancer a non-significant difference in disease-free or overall survival was observed . Distant metastases developed in 76 % , while local recurrence alone occurred in 14 % . An early start of adjuvant treatment ( < 4 weeks ) did not affect results . Compliance to 5FU plus levamisole  was 69 % . Severe toxicity did not occur . In conclusion , one year 5FU plus levamisole was of benefit in stage II and III colonic cancer ; in rectal cancer a significant positive effect could not be demonstrated . © 2001 Cancer Research Campaign BACKGROUND The conviction that postoperative radiotherapy and chemotherapy represent an acceptable st and ard of care for patients with Dukes ' B ( stage II ) and Dukes ' C ( stage III ) carcinoma of the rectum evolved in the absence of data from clinical trials design ed to determine whether the addition of radiotherapy results in improved disease-free survival and overall survival . This study was carried out to address this issue . An additional aim was to determine whether leucovorin (LV)-modulated 5-fluorouracil ( 5-FU ) is superior to the combination of 5-FU , semustine , and vincristine ( MOF ) in men . PATIENTS AND METHODS Eligible patients ( n = 694 ) with Dukes ' B or C carcinoma of the rectum were enrolled in National Surgical Adjuvant Breast and Bowel Project ( NSABP ) Protocol R-02 from September 1987 through December 1992 and were followed . They were r and omly assigned to receive either postoperative adjuvant chemotherapy alone ( n = 348 ) or chemotherapy with postoperative radiotherapy ( n = 346 ) . All female patients ( n = 287 ) received 5-FU plus LV chemotherapy ; male patients received either MOF ( n = 207 ) or 5-FU plus LV ( n = 200 ) . Primary analyses were carried out by use of a stratified log-rank statistic ; P values are two-sided . RESULTS The average time on study for surviving patients is 93 months as of September 30 , 1998 . Postoperative radiotherapy result ed in no beneficial effect on disease-free survival ( P = .90 ) or overall survival ( P = .89 ) , regardless of which chemotherapy was utilized , although it reduced the cumulative incidence of locoregional relapse from 13 % to 8 % at 5-year follow-up ( P = .02 ) . Male patients who received 5-FU plus LV demonstrated a statistically significant benefit in disease-free survival at 5 years compared with those who received MOF ( 55 % versus 47 % ; P = .009 ) but not in 5-year overall survival ( 65 % versus 62 % ; P = .17 ) . CONCLUSIONS The addition of postoperative radiation therapy to chemotherapy in Dukes ' B and C rectal cancer did not alter the subsequent incidence of distant disease , although there was a reduction in locoregional relapse when compared with chemotherapy alone Background We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer , using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil ( carmofur , HCFU ) and uracil/tegafur ( UFT ) . Methods Patients with stage II , III , or IV ( Dukes ’ B , C ) colorectal cancer were enrolled and r and omly assigned to one of three groups : an immunochemotherapy group ( mitomycin C [ MMC ] + 5-fluorouracil [ 5-FU ] + HCFU + OK-432 ) , a chemotherapy group ( MMC + 5-FU + HCFU ) , and a control group ( surgery alone ) for those with colon cancer ( study 1 ) ; and an immunochemotherapy group ( MMC + 5-FU + UFT + OK-432 ) , a chemotherapy group ( MMC + 5-FU + UFT ) , and a control group ( surgery alone ) for those with rectal cancer ( study 2 ) . Results A total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this r and omized clinical trial ( RCT ) . The incidence of side-effects was in the order of : immunochemotherapy group ≫ chemotherapy group ≫ control group in both the cohort of patients with colon cancer and the cohort with rectal cancer . In particular , the frequency of leucopenia and skin disorders was significantly higher than control groups . There were no severe adverse events such as death related to the adjuvant therapy . In both the colon cancer and rectal cancer cohorts , no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups . Conclusion The results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer , but that both combinations were well tolerated as adjuvant therapy Colorectal cancer is one of the major malignant diseases and , recently , its incidence appears to be increasing . Surgical resectability is an important prognostic determinant ; however , recurrent tumors are commonly noted , even after apparently curative surgery . Because such metastatic disease can not be cured , better adjuvant therapies are urgently called for A prospect i ve controlled r and omized trial testing adjuvant postoperative combination chemotherapy ( 5‐fluorouracil , lomustine ( CNU ) and vincristine ) versus no adjuvant therapy in patients operated on for Dukes ' C colorectal cancer is reported . In total 334 patients aged less than 70 years were recruited : 205 patients with colonic and 99 with rectal cancer , but there were three protocol violations and these cases are excluded from further consideration . Twenty‐seven patients had a limited resection of their cancer . After 5 years follow‐up there was no significant difference in the tumour‐free survival rate or in the survival rate between the treated and control groups . Twenty‐nine of the 147 patients who started chemotherapy  discontinued this treatment because of side‐effects , mainly from the gastrointestinal tract . In 30 patients treatment was discontinued because of recurrent disease . The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice Twelve hundred ninety-six patients with resected colon cancer that either was locally invasive ( Stage B2 ) or had regional nodal involvement ( Stage C ) were r and omly assigned to observation or to treatment for one year with levamisole combined with fluorouracil .  Patients with Stage C disease could also be r and omly assigned to treatment with levamisole alone . The median follow-up time at this writing is 3 years ( range , 2 to 5 1/2 ) . Among the patients with Stage C disease , therapy with levamisole plus fluorouracil reduced the risk of cancer recurrence by 41 percent ( P less than 0.0001 ) . The overall death rate was reduced by 33 percent ( P approximately 0.006 ) . Treatment with levamisole alone had no detectable effect . The results in the patients with Stage B2 disease were equivocal and too preliminary to allow firm conclusions . Toxic effects of levamisole alone were infrequent , usually consisting of mild nausea with occasional dermatitis or leukopenia , and those of levamisole plus fluorouracil were essentially the same as those of fluorouracil alone -- i.e . , nausea , vomiting , stomatitis , diarrhea , dermatitis , and leukopenia . These reactions were usually not severe and did not greatly impede patients ' compliance with their regimen . We conclude that adjuvant therapy with levamisole and fluorouracil should be st and ard treatment for Stage C colon carcinoma . Since most patients in our study were treated by community oncologists , this approach should be readily adaptable to conventional medical practice PURPOSE The combination of radiation therapy with fluorouracil (5-FU)-based chemotherapy is generally accepted as appropriate postoperative therapy for patients with adenocarcinomas of the rectum that extend through the bowel wall or with lymph nodes positive for tumor . We attempted to determine whether the efficacy of this postoperative therapy could be improved by the addition of leucovorin and /or levamisole . METHODS A total of 1,696 patients were r and omized and eligible for treatment with one of four treatment schemes . All patients received two cycles of bolus 5-FU-based systemic chemotherapy followed by pelvic radiation therapy with chemotherapy and two more cycles of the same systemic chemotherapy . Chemotherapy was either 5-FU alone , 5-FU with leucovorin , 5-FU with levamisole , or 5-FU with leucovorin and levamisole . RESULTS With a median follow-up duration of 48 months , there is no statistically significant advantage to any of the treatment regimens compared with bolus 5-FU alone . There is evidence of increased gastrointestinal toxicity with the three-drug combination compared with bolus 5-FU alone . Statistical analysis suggests it is very unlikely that either levamisole-containing combination will be shown to be of value with further follow-up evaluation . CONCLUSION There is no evidence at present for a beneficial effect of levamisole in the adjuvant treatment of rectal cancer . Definitive evaluation of the effect of the addition of leucovorin to 5-FU and pelvic radiation will require further follow-up evaluation Information is presented from 555 patients with Dukes B and C rectal cancers treated by curative resection who were entered into the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) protocol R-01 between November 1977 and October 1986 . Their average time on study was 64.1 months . The patients were r and omized to receive no further treatment  ( 184 patients ) , postoperative adjuvant chemotherapy with 5-fluorouracil , semustine , and vincristine ( MOF ) ( 187 patients ) , or postoperative radiation therapy ( 184 patients ) . The chemotherapy group , when compared with the group treated by surgery alone , demonstrated an overall improvement in disease-free survival ( P = .006 ) and in survival ( P = .05 ) . Employing the proportional hazards model , a global test was used to determine the presence of treatment interactions . Investigation of stratification variables employed in this study indicated that sex , and to a lesser extent age and Dukes stage , made individual contributions to the disease-free survival and the survival benefit from chemotherapy . When evaluated according to sex , the benefit for chemotherapy at 5 years , both in disease-free survival ( 29 % vs. 47 % ; P less than .001 ; relative odds , 2.00 ) and in survival ( 37 % vs. 60 % ; P = .001 ; relative odds , 1.93 ) , was restricted to males . When males were tested for age trend with the use of a logistic regression analysis , chemotherapy was found to be more advantageous in younger patients . When the group receiving post-operative radiation ( 4,600 - 4,700 rad in 26 - 27 fractions ; 5,100 - 5,300 rad maximum at the perineum ) was compared to the group treated only by surgery , there was an overall reduction in local-regional recurrence from 25 % to 16 % ( P = .06 ) . No significant benefit in overall disease-free survival ( P = .4 ) or survival ( P = .7 ) from the use of radiation has been demonstrated . The global test for interaction to identify heterogeneity of response to radiation within subsets of patients was not significant . In conclusion , this investigation has demonstrated a benefit from adjuvant chemotherapy ( MOF ) for the management of rectal cancer . The observed advantage was restricted to males . Postoperative radiation therapy reduced the incidence of local-regional recurrence , but it failed to affect overall disease-free survival and survival In a prospect ively r and omized study , the effect of adjuvant chemotherapy with 5-FU on survival and recurrence rates was analyzed in 299 evaluable patients with colorectal carcinoma who either underwent a curative or a palliative resection . In the treatment group , chemotherapy consisted of the intravenous administration of 12 mg/kg daily of 5-FU for 4 consecutive days , then 6 mg/kg on alternate days , to the point of toxicity , or to a maximum of five doses , followed by 12mg/kg weekly for 1 year . Some degree of drug toxicity was seen in the majority of patients , was rarely severe , and there have been no drug-related deaths . Analysis of the survival curves and disease-free interval curves reveal definite evidence of drug benefit in two unfavorable subgroups , namely patients with Dukes C tumors and in patients whose tumor was located in the rectum . In the chemotherapy groups , patients who were treated to toxicity ( WBC less than 4000 mm3 ) , the disease-free interval was significantly longer than the nonleukopenic patients . We conclude that the addition of 5-FU to the surgical treatment of colorectal carcinoma provides a small , but significant benefit in patients with colorectal cancer in certain unfavorable subgroups , namely patients with Dukes C lesions and patients with rectal carcinoma Postoperative adjuvant chemotherapy reportedly improves advanced colorectal cancer patients ' survival , however , it is necessary to assess what regimens are useful . Doxifluridine ( 5'-DFUR ) is an intermediate of capecitabine approved in Europe and USA to treat metastatic colorectal cancer .  5'-DFUR is metabolized to 5-fluorouracil ( 5-FU ) by thymidine phosphorylase existing in tumor at high concentrations , suggesting high 5-FU levels in tumor tissues and lesser complications . Present study compared usefulness of 5'-DFUR to that of oral 5-FU .  Patients were enrolled at 38 centers from April 1993 to September 1996 . They had diagnosed colorectal cancer of TNM stages II and III , and underwent macroscopic curative resection . Patients were prestratified into colon or rectum cancer and allocated into either 5'-DFUR ( 5'-DFUR 460 mg/m(2)/day + PSK 3 g/day ) or 5-FU ( 5-FU 115 mg/m(2)/day + PSK 3 g/day ) group by dynamic r and omization ( stratification factors such as depth of tumor , degree of lymph node metastasis , and location of tumor ) . Drugs were orally administered daily from postoperative week 2 to 54 , with 6 mg/m(2 ) mitomycin C at operation and following days . Subjects for analysis were 277 in 5'-DFUR and 281 in 5-FU groups . Median follow-up was 6.5 years . Although no differences in overall survival curves were detected , multivariate analysis showed that 5'-DFUR + PSK regimen was a significantly better prognostic factor in patients with Dukes B or C ( risk ratio , 1.451 ; p=0.048 ) ; with tumor depth of pT3 or pT4 ( risk ratio , 1.568 ; p=0.020 ) . For patients with advanced colorectal cancer , 5'-DFUR + PSK therapy may possibly be more useful than 5-FU + PSK , but further study is required A prospect ively r and omised controlled clinical trial of adjuvant therapy was undertaken , at a single-centre , population -based cancer institute , in patients with Dukes ' stages B2 and C colorectal carcinoma after curative surgery . Between 1976 and 1983 , 253 patients were r and omised to either control ( no further therapy after surgery ) , immunotherapy ( oral bacille Calmette-Guérin [ BCG ] 120 mg once a month ) for 5  years or chemoimmunotherapy ( oral BCG as above with methyl-cyclohexyl-chloroethyl nitrosourea [ meCCNU ] 130 mg/m2 on day 1 and 5-fluorouracil [ 5-FU ] 325 mg/m2/day on days 1 - 5 and 375 mg/m2/day on days 36 - 40 ) repeated every 10 weeks for 8 cycles . The median follow-up of patients is now 6.95 years . Of the control , immunotherapy , and chemoimmunotherapy groups 22.35 % , 39.28 % , and 28.57 % , respectively , have relapsed . The log-rank analysis of results shows no disease-free or overall survival advantage for patients receiving adjuvant therapy compared with the control group . Patients receiving adjuvant immunotherapy for stage B2 appear to have a significantly inferior disease-free survival compared with other groups , but their overall survival is similar . There are no significant differences in disease-free or overall survival in the three groups of patients with stage C tumour . Of 82 patients dying , 78.05 % died of progressive colorectal carcinoma , 13 patients developed a second malignancy ; the remainder died of seemingly unrelated causes A prospect i ve controlled study , the 7th cooperative study of the Japanese Foundation for Multidisciplinary Treatment , was conducted to evaluate the usefulness of concomitant therapy with MMC + HCFU as a postoperative adjuvant therapy in patients with colorectal cancer who had undergone curative resection for a period of 2 years and 11 months from February , 1986 . The Dukes B and C patients with colorectal cancer classified by macroscopic examination who had an intravenous MMC 6 mg/m2 on the day of operation and followed by oral HCFU for 12 months from 2 weeks after operation ( Group X ) were compared with patients who had operation only ( Group Y ) . Some 978 patients with colon cancer and 713 patients with rectal cancer were enrolled in the study , 85 ( 5.0 % ) of whom were not eligible . The 5-year survival rate of Group X in colon cancer was 79.3 % and that of Group Y was 76.4 % : thus the survival rate of Group X was slightly better than that of Group Y , but no significant difference was found between the two groups . Subset analysis revealed that the survival rate of Group X in advanced cancer of stage III b + IV , according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon , Rectum and Anus in Japan , was 62.4 % and that of Group Y was 46.2 % . Thus , the survival rate of Group X was significantly better than that of Group Y ( logrank test : p = 0.035 , generalized Wilcoxon test : p = 0.025 ) . The disease-free survival rate was not significantly different between the groups with colon cancer and rectal cancer . The above results suggest that HCFU is useful for patients with a high risk of recurrence who had advanced colon cancer ( stage III b + IV ) . However , additional prospect i ve studies are required to verify them One thous and two hundred fifty-four cases ( 610 colonic and 644 rectal cancers resected during 2 years from 1984 and followed up for more than 5 years ) were entered from 140 institutions in Japan and analyzed by means of Cox 's proportional hazards model . The analyzed pathologic variables were the size and depth of invasion , Dukes ' stage , venous invasion , lymphatic permeation , and other clinical features , such as the sex and age of the patient and location of the tumor . The extent of dissection , serum carcinoembryonic antigen ( CEA ) level , and the presence or absence of adjuvant chemotherapy were also analyzed . Adjuvant chemotherapy consisted of three arms for both colonic and rectal cancers . For colonic cancer , arm I was a combination of i.p . ( intraportal ) and i.v . mitomycin C ( MMC ) + p.o . 5-fluorouracil ( 5-FU ) ; arm II was i.v . MMC + p.o . 5-FU ; and arm III was surgery only . For rectal cancer , arm IV was a combination of i.a . ( inferior mesenteric artery ) and i.v . MMC + p.o . 5-FU ; arm V was i.v . MMC + p.o . 5-FU ; and arm VI was surgery only . As for the factors affecting the disease-free survival of the patient , multivariate analysis disclosed nodal involvement , venous invasion , an elevated CEA level , and the lower part of the rectum . The effect of adjuvant chemotherapy on the patient 's survival was proven for rectal cancer but not for colonic cancer . We conclude that these factors should be considered in setting the stage of tumor pre- and postoperatively BACKGROUND Although surgical resectability is an important prognostic factor , recurrences are commonly noted in advanced colorectal cancer patients , even after apparently curative surgery . Since such recurrences can not be cured , better adjuvant chemotherapies are urgently required . PATIENTS AND METHODS We studied the effect of post-operative chemotherapy using oral administration of 1-hexylcarbamoyl-5-fluorouracil ( HCFU ) with 5-fluorouracil ( 5-FU ) infusion for curatively-resected Stage IIIa and IIIb colorectal cancers . This study was prospect ively r and omized and controlled and 314 ( 97.8 % ) out of 321 patients were determined to be c and i date s for statistical assessment . Group A and Group B received 5-FU intravenous injection at , respectively , 333 mg/m2 and 1000 mg/m2 body surface area/24 hours continuously for 72 hours beginning on post-operative day 0 and day 6 , with oral HCFU 300 mg daily for 52 weeks beginning 2 weeks after surgery . RESULTS There were no differences in overall 5-year survival or disease-free survival between Group A and Group B. A retrospective subset analysis . however , suggested that the protocol of Group B tended to yield better 5-year survival ( 68.3 % ) for rectal cancer than that of Group A ( 58.8 % ) . CONCLUSION Inductive therapy with high-dose 5-FU in combination with oral HCFU appears to be beneficial as adjuvant chemotherapy for advanced rectal cancer with lymph node metastasis PURPOSE The European Organisation for Research and Treatment of Cancer ( EORTC ) trial evaluated the addition of chemotherapy ( CT ) to preoperative radiation ( preop RT ) and the value of postoperative CT for improving the survival in patients with T3 - 4 resectable rectal cancer . Patients were allocated to the following four arms : arm 1 , preop RT 45 Gy in 5 weeks ; arm 2 , preop RT plus two 5-day CT courses ( fluorouracil 350 mg/m2/d and leucovorin 20 mg/m2/d ) in the first and fifth week of RT ; arm 3 , preop RT plus four postoperative CT courses ; and arm 4 , preop RT and CT plus postoperative CT . We investigated the effect of adding CT on the pathologic parameters . PATIENTS AND METHODS One thous and eleven patients were entered onto the trial ; 505 received preop RT ( arms 1 and 3 ) , and 506 received preop RT-CT ( arms 2 and 4 ) . We analyzed the differences in tumor size , tumor node stage , number of retrieved nodes , and histologic features such as lymphatic , venous , and perineural invasions , tumor differentiation , and tumor type . RESULTS After preop RT-CT , tumors were smaller ( P < .0001 ) , had less advanced pT ( P < .001 ) and pN stages ( P < .001 ) , had small numbers of examined nodes ( P = .046 ) , and less frequent LVN invasions ( P < or = .008 ) . Mucinous tumors increased after preop RT-CT ( P < .001 ) . CONCLUSION In patients with rectal cancer , preliminary results of EORTC Trial 22921 indicate that the addition of CT to preop RT induces down-sizing , downstaging , and significant changes in histologic characteristics . Longer follow-up is needed to assess the impact on local control and survival A r and omized controlled study was carried out by the envelope method with 491 institutions in participation across the country in order to find an optimal  surgical adjuvant chemotherapy for curatively resected colorectal cancer . The schedules for drug administration were different in four districts :  ACNU + Futraful ( FT ) group and FT alone group in the Hokkaido-Shikoku district ; the same schedule groups plus untreated group  in the Chubu-Kinki district ;  MMC+FT group , FT alone group  in the Tohoku-Kanto district ; and ADM+FT group and FT alone group in the Chugoku-Kyushu district . The numbers of patients admitted to this study were 2,450 cases with colon cancer and 2,456 cases met the evaluation criteria of this study . The 5-year survival rate on the whole did not differ from combination therapy to single drug therapy in either colon cancer or rectal cancer , but in Dukes C rectal cancer the five-year survival rate tended to be higher with the combination therapies . In n2 ( + ) or a2(s ) rectal cancer in particular , combination therapies with MMC and FT and with ADM and FT achieved significantly higher five-year survival rate , and the rate of local recurrence was significantly lower with ADM+FT BACKGROUND Combined radiation therapy and chemotherapy after surgery , compared with postsurgical radiation therapy alone , has been shown to improve disease-free survival and overall survival significantly among patients with poor-prognosis ( i.e. , advanced stage disease or metastasis to regional lymph nodes ) resectable rectal cancer . However , the combined therapy is associated with more toxic effects , raising the question of whether the benefits of the treatment justify its quality -of-life costs for the individual patient . PURPOSE To assess the trade-offs between improved survival and increased treatment toxicity , we reanalyzed data from a r and omized clinical trial that compared the efficacy of combined adjuvant chemotherapy and radiation therapy with adjuvant radiation therapy alone in the treatment of patients with poor-prognosis resectable rectal cancer . METHODS The data were from a North Central Cancer Treatment Group trial in which 204 patients with poor-prognosis rectal cancer were r and omly assigned to receive either postoperative radiation therapy alone or radiation therapy plus fluorouracil-based chemotherapy . A quality -adjusted time without symptoms or toxicity ( Q-TWiST ) analysis was used to account for freedom from symptomatic disease and from early and late side effects of treatment . All reported P values are two-sided . RESULTS As reported previously , the combined therapy reduced the risk of relapse by 34 % ( 95 % confidence interval [ CI ] = 12%-50 % ; P = .0016 ) and reduced the overall death rate by 29 % ( 95 % CI = 7%-45 % ; P = .025 ) in comparison with adjuvant radiation therapy alone . In the 5 years following assignment to treatment , patients who received the combined therapy had more time with toxicity ( 3.1 months ; 95 % CI = 2.0 - 4.1 months ) , shorter survival after relapse ( 3.6 months less ; 95 % CI = 0.9 - 6.3 months less ) , and more TWiST ( 6.1 months ; 95 % CI = 0.2 - 12.0 months ) than patients who received adjuvant radiation therapy alone . Despite an increase in the amount of time that individuals spent with early and late toxic effects , the Q-TWiST analysis indicated that the combined therapy conferred significantly greater benefit for a wide range of patient preferences about living with the toxicity of treatment or the symptoms of overt disease . CONCLUSIONS AND IMPLICATION S Use of combined chemotherapy and radiation therapy as an adjuvant to surgery for patients with poor-prognosis resectable rectal cancer is justified , since the improved outcome in terms of delayed recurrence and increased survival balances the time spent with early and late toxic effects . The Q-TWiST method is an excellent way to compare treatment outcomes that include quality -of-life considerations PURPOSE In 1992 , preoperative radiotherapy was considered in France as the st and ard treatment for T3 - 4 rectal cancers . The present r and omized trial compares preoperative radiotherapy with chemoradiotherapy . PATIENTS AND METHODS Patients were eligible if they presented a resectable T3 - 4 , Nx , M0 rectal adenocarcinoma accessible to digital rectal examination .  Preoperative radiotherapy with 45 Gy in 25 fractions during 5 weeks was delivered . Concurrent chemotherapy with fluorouracil 350 mg/m2/d during 5 days , together with leucovorin , was administered during the first and fifth week in the experimental arm . Surgery was planned 3 to 10 weeks after the end of radiotherapy . All patients should receive adjuvant chemotherapy with the same fluorouracil/leucovorin regimen . The primary end point of the trial was overall survival . RESULTS A total of 733 patients were eligible .  Grade 3 or 4 acute toxicity was more frequent with chemoradiotherapy ( 14.6 % v 2.7 % ; P < .05 ) . There was no difference in sphincter preservation . Complete sterilization of the operative specimen was more frequent with chemoradiotherapy ( 11.4 % v 3.6 % ; P < .05 ) . The 5-year incidence of local recurrence was lower with chemoradiotherapy ( 8.1 % v 16.5 % ; P < .05 ) . Overall 5-year survival in the two groups did not differ . CONCLUSION Preoperative chemoradiotherapy despite a moderate increase in acute toxicity and no impact on overall survival significantly improves local control and is recommended for T3 - 4 , N0 - 2 , M0 adenocarcinoma of the middle and distal rectum BACKGROUND AND PURPOSE The aim was to verify whether preoperative conventionally fractionated chemoradiation offers an advantage in sphincter preservation in comparison with preoperative short-term irradiation . PATIENTS AND METHODS Patients with resectable T3 - 4 rectal carcinoma without sphincters ' infiltration and with a lesion accessible to digital rectal examination were r and omised into :  preoperative 5x5Gy short-term irradiation with subsequent total mesorectal excision ( TME ) performed within 7 days or chemoradiation to a total dose of 50.4Gy ( 1.8Gy per fraction ) concomitantly with two courses of bolus 5-fluorouracil and leucovorin followed by TME after 4 - 6 weeks . Surgeons were obliged to base the type of operation on the tumour status at the time of surgery . RESULTS Between 1999 and 2002 , 316 patients from 19 institutions were enrolled . The sphincter preservation rate was 61 % in the 5x5Gy arm and 58 % in the radiochemotherapy arm , P = 0.57 . The tumour was on average 1.9 cm smaller ( P < 0.001 ) among patients treated with chemoradiation compared with short-term schedule . For patients who underwent sphincter-preserving procedure , the surgeons generally followed the rule of tailoring the resection according to tumour downsizing ; the median distal bowel margin was identical ( 2 cm ) for both r and omised groups . However , in the chemoradiation group , five patients underwent abdominoperineal resection despite clinical complete response . CONCLUSIONS Despite significant downsizing , chemoradiation did not result in increased sphincter preservation rate in comparison with short-term preoperative radiotherapy . The surgeons ' decisions were subjective and based on pre-treatment tumour volume at least in clinical complete responders Local control and survival following surgical treatment of rectal cancer have been improved by the introduction of total mesorectal excision ( TME ) . The aim of this study was to determine the nationwide impact of the introduction and training of TME on recurrence and survival in rectal cancer Purpose : The objective of this exp and ed phase II trial was to confirm the safety results of the preceding phase I study and establish the efficacy of neoadjuvant radiochemotherapy with capecitabine in rectal cancer in a multicenter setting . Patients and Methods : 96 patients ( 63 % male , age 34–81 years ) with advanced rectal cancer ( cT3–4 or cN+ ) from seven university centers in Germany were recruited . All were to receive a total irradiation dose of 50.4–55.8 Gy with conventional fractions . Capecitabine was given at an oral dosage of 825 mg/m2bid on each day of the radiotherapy period with the first daily dose applied 2 h before irradiation , followed by surgery 6 weeks later . Results : Most of the patients suffered from an advanced primary tumor ( cT3 : 57 % , cT4 : 40 % ) with lymph node involvement in 60 % . After neoadjuvant treatment , with a mean of 99 % of the scheduled radiation dose actually delivered , a clinical response rate of 68 % ( 95 % confidence interval : 57–78 % ) was observed . Out of 87 evaluable patients undergoing surgery , a sphincter-preserving procedure could be performed in 51 % and R0 resection in 94 % . A pathologically complete response was achieved in six patients ( 7 % , 95 % confidence interval : 3–14 % ) . The comparison of initial diagnosis and pathologic findings showed a downstaging in 61 % . Acute toxicity with > 5 % incidence of NCI ( National Cancer Institute ) grade ≥ 3 included lymphopenia ( 12 % ) , leukopenia ( 6 % ) , and diarrhea ( 7 % ) . Mild to moderate h and -foot syndrome occurred in 12 % only . After a median follow-up of 48 months , the 5-year overall survival and tumor control data were , with regard to patient selection , in the expected range with an overall survival of 65 % , a relapse-free survival of 47 % , and a local recurrence rate after 5 years of 17 % . Conclusion : The data clearly confirm that capecitabine is an adequate substitute for 5-fluorouracil in preoperative chemoradiation of rectal cancer with a favorable safety profile . Ziel : Diese multizentrische Phase-II-Studie sollte Effektivität und Toxizität einer neoadjuvanten Radiochemotherapie mit Capecitabine prüfen . Patienten und Method ik:96 Patienten ( davon 63 % männlich , Alter 34–81 Jahre ) mit lokal fortgeschrittenem Rektumkarzinom ( cT3–4 oder cN+ ) aus sieben deutschen Universitätskliniken wurden rekrutiert . Alle erhielten eine präoperative Radiotherapie ( 50,4–55,8 Gy in konventioneller Fraktionierung mit 5 × 1,8 Gy ) und zusätzlich 2 × täglich 825 mg/m2Capecitabin während gesamten Radiotherapie ( erste Dosis 2 h vor Radiotherapie , keine Pause am Wochenende ) . 6 Wochen nach der Radiochemotherapie war die Resektion geplant . Ergebnisse:97 % der Patienten hatten T3/T4-Tumoren ( T3 : 57 % ; T4 : 40 % ) . Lymphknotenbefall ( cN+ ) lag in 60 % vor . Die präoperative Therapie war gut durchführbar ( mittlere Strahlendosis 99 % , mittlere Capecitabindosis 96 % der geplanten Dosis ) . Die klinische Ansprechrate betrug 68 % ( 95%-Konfidenzintervall : 57–78 % ) und entsprach der Studienhypothese . Von 87 auswertbaren operierten Patienten wurden 94 % R0-reseziert ; ein Sphinktererhalt war in 51 % möglich . Sechs Patienten ( 7 % , 95%-Konfidenzintervall : 3–14 % ) hatten eine histologisch komplette Remission ( ypT0 ) i m Resektat . Ein Downstaging wurde in 61 % erreicht . Akute Nebenwirkungen CTC-Grad ≥ 3 ( Common Toxicity Criteria ) mit einer Frequenz von > 5 % wurden für Lymphopenie ( 12 % ) , Diarrhö ( 7 % ) und Leukopenie ( 6 % ) beobachtet . Ein H and -Fuß-Syndrom trat in 12 % auf und war jeweils nur mild ( Grad 1–2 ) . Die 5-Jahres-Überlebensrate betrug 65 % , das rezidivfreie Überleben 47 % und die lokale Kontrolle nach 5 Jahren 83%.Schlussfolgerung : Die Date n dieser multizentrischen Phase-II-Studie bestätigen , dass die Kombination von präoperativer Radiotherapie und Capecitabin eine wirksame und nebenwirkungsarme Beh and lung beim lokal fortgeschrittenen Rektumkarzinom darstellt . Capecitabin eignet sich als Ersatz für eine kontinuierliche 5-Fluorouracil-Infusion In a Central Oncology Group trial in 319 evaluable patients the addition of 5-FU to the surgical treatment of colorectal carcinoma provided a small but significant benefit in those with colotectal cancer in certain unfavorable situations , namely Dukes C tumors and rectal carcinoma Background : Postoperative adjuvant chemoradiation treatment after curative resection for rectal cancer was needed to reduce recurrence and improve a survival rate . Intravenous 5-fluorouracil ( 5-FU ) and leucovorin has been a mainstay of chemotherapy , but oral 5-FU derivatives have been shown a comparable antitumor activity . Intravenous 5-FU and oral doxifluridine were compared with respect to therapeutic efficacy , drug toxicity , and quality of life . Methods : A total of 166 patients were r and omized to receive intravenous 5-FU ( 450 mg/m2/day ) or oral doxifluridine ( 900 mg/m2/day ) in combination with leucovorin ( 20 mg/m2/day ) for depth of invasion , nodal status , metastasis ( TNM ) stage II and III patients between October 1997 and February 1999 . Consecutive daily intravenous infusion for 5 days per every month for a total of 12 cycles ( IV arm , n = 74 ) and oral doxifluridine daily for 3 weeks and 1 week rest for a total of 12 cycles ( oral arm , n = 92 ) . Drug toxicity and quality of life were observed . Quality of life was scored according to 22 daily activity items ( good , ≥ 71 ; fair , < 70 ; poor , < 52 ) . Results : There was no difference of sex between two groups ( IV arm : male/female = 45/29 , oral arm : male/female = 59/33 ) . The mean age was 52.3 vs. 59.5 , respectively . There was also no difference of TNM stage distribution and type of operation between groups ( P = .05 ) . Mean numbers of chemotherapy cycles were 6.5 ± 3.7 ( IV arm ) vs. 7.2 ± 4.3 ( oral arm ) , respectively . The rate of recurrence was 9/74 ( 12.1 % ) in the IV arm and 6/92 ( 6.5 % ) in the oral arm , respectively ( P = .937 ) . Local recurrence was 2/74 ( stage III ; 2.7 % ) in the IV arm and 1/92 ( stage II;1.1 % ) in the oral arm , respectively . Systemic recurrence was 7/74 ( stage III ; 9.4 % ) in the IV arm and 5/92 ( stage III ; 5.4 % ) in the oral arm , respectively . The most common site of systemic recurrence was the liver . Toxicity profile was as follows : leukopenia ( 30/74 vs. 17/92 ) and alopecia ( 21/74 vs. 13/92 ) were statistically more common in the IV arm . Diarrhea was more common in the oral arm . Poor quality of life score between two groups was observed at 1 month ( 23.9 % vs. 13 % ) and 2 months ( 15.8 % vs. 3.7 % ) after chemotherapy . Good quality of life score was observed at 1 month ( 19.5 % vs. 49 % ) and 2 months ( 47 % vs. 72 % ) , respectively ( P < .05 ) . Conclusions : Oral doxifluridine with leucovorin shows a comparable therapeutic efficacy to intravenous 5-FU regimen with high quality of life as postoperative adjuvant therapy . The oral regimen also can be safely given with appropriate toxicity and tolerability PURPOSE To evaluate the rate of pathologic complete response and toxicity of neoadjuvant chemoradiation for advanced T3/T4 distal rectal cancers in a r and omized phase II study PATIENTS AND METHODS Patients with clinical T3/T4 distal rectal cancers were r and omly assigned in a phase II study to receive combined neoadjuvant chemoradiotherapy followed by surgical resection . Patients were r and omly assigned to receive continuous venous infusion ( CVI ) fluorouracil ( FU ) 225 mg/m2 per day , 7 days per week , plus pelvic hyperfractionated radiation 55.2 to 60 Gy at 1.2 Gy bid ( arm 1 ) or CVI FU 225 mg/m2 per day Monday to Friday , 120 hours per week plus irinotecan 50 mg/m2 once weekly for 4 weeks plus pelvic radiation therapy 50.4 to 54 Gy at 1.8 Gy per day ( arm 2 ) . Surgery was performed 4 to 10 weeks after completion of neoadjuvant therapy . The primary end point of this study was pathologic complete response ( pCR ) . Secondary end points included acute and late normal tissue morbidity . RESULTS A total of 106 patients were entered onto the study , with 103 assessable for response . The overall resectability rate was 93 % . The median time to surgery was 7 weeks . Tumor downstaging was observed in 78 % of patients in both arms . The pCR rate for all assessable patients was 26 % in each arm . For patients who had surgery , the pCR rate was also the same ( 28 % ) in both arms . Acute and late toxicity was also similar . Grade 3 and 4 acute hematologic and nonhematologic toxicity occurred in 13 % and 38 % in arm 1 and 12 % and 45 % in arm 2 , respectively . CONCLUSION Although the overall complete response rate and toxicity seems similar in both arms , this is the first multi-institutional study to establish a relatively high ( 28 % ) pCR rate after neoadjuvant therapy BACKGROUND Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival . In a previous study , combined radiation and chemotherapy improved survival significantly as compared with surgery alone , but not as compared with adjuvant radiation , which many regard as st and ard therapy . We design ed a combination regimen to optimize the contribution of chemotherapy , decrease recurrence , and improve survival as compared with adjuvant radiation alone . METHODS Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were r and omly assigned to postoperative radiation alone ( 4500 to 5040 cGy ) or to radiation plus fluorouracil , which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine ( methyl-CCNU ) . RESULTS After a median follow-up of more than seven years , the combined therapy had reduced the recurrence of rectal cancer by 34 percent ( P = 0.0016 ; 95 percent confidence interval , 12 to 50 percent ) . Initial local recurrence was reduced by 46 percent ( P = 0.036 ; 95 percent confidence interval , 2 to 70 percent ) , and distant metastasis by 37 percent ( P = 0.011 ; 95 percent confidence interval , 9 to 57 percent ) . In addition , combined therapy reduced the rate of cancer-related deaths by 36 percent ( P = 0.0071 ; 95 percent confidence interval , 14 to 53 percent ) and the overall death rate by 29 percent ( P = 0.025 ; 95 percent confidence interval , 7 to 45 percent ) . Its acute toxic effects included nausea , vomiting , diarrhea , leukopenia , and thrombocytopenia . These effects were seldom severe . Severe , delayed treatment-related reactions , usually small-bowel obstruction requiring surgery , occurred in 6.7 percent of all patients receiving radiation , and the frequencies of these complications were comparable in both treatment groups . CONCLUSIONS The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis , as compared with postoperative radiation alone BACKGROUND A joint study was performed by the Tokai HCFU study group , which included seven institutions , to examine the value of oral administration of Carmofur ( HCFU ) , a 5-fluorouracil ( 5-FU ) derivative , for postoperative adjuvant chemotherapy in patients with colorectal cancer undergoing curative resection . METHODS The patients were divided into two groups , a control group receiving no HCFU and a group administered HCFU for 1 year , using a central ized registration system by telephone . Among 173 patients entered into this study , 159 evaluable cases were analyzed for evaluation of the drug . RESULTS The cumulative 5-year disease-free rate of patients who received HCFU was significantly increased compared with the control group . In particular , the rate was much higher in patients with colon cancer .  No severe side effects arose from adjuvant chemotherapy with HCFU . CONCLUSION Adjuvant chemotherapy with oral HCFU appears to provide a useful and safe postoperative treatment An adjuvant program of fluorouracil 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 were r and omly assigned to an intraluminal fluorouracil 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 . Those patients receiving intraluminal fluorouracil ( 30 mg/kg ) received intravenous fluorouracil ( 10 mg/kg ) on each of the first two postoperative days and five subsequent postoperative courses of oral fluorouracil ( 90 mg/kg ) in each 18-day course over a one-year period . By July 1 , 1975 , there were 203 patients undergoing curative resection entered into the study .  Survival and disease-free data , as of Dec 31 , 1976 , revealed no benefit from this adjuvant course of fluorouracil . These data support the need for continued r and omized clinical trials of new and innovative adjuvant therapy compared with an untreated control group BACKGROUND The aim of this study was to determine whether the efficacy of the combination of 5-fluorouracil ( 5-FU ) , leucovorin ( LV ) and radiation therapy ( RT ) could be improved by the addition of interferon-alpha2b ( IFN-alpha ) in patients who have had a ' curative ' resection , for rectal adenocarcinoma ( Dukes ' B2/C ; T3 N0 , T4 N0 , N1 - 3 ) . PATIENTS AND METHODS A total of 207 eligible patients with a performance status of 0 or 1 were r and omized postoperatively between days 21 and 70 to one of the two treatment groups : group A , LV 20 mg/m2 i.v . bolus and 5-FU 425 mg/m2 i.v . days 1 - 5 and 29 - 33 , LV 20 mg/m2 and 5-FU 400 mg/m2 days 57 - 60 and 85 - 88 , LV 20 mg/m2 and 5-FU 380 mg/m2 days 1 - 5 and 29 - 33 with the second day 1 occurring 28 days after the completion of RT ( 45 Gy ) ; group B , LV , 5-FU and RT as in group A , and IFN-alpha 5 x 10(6 ) IU s.c . three times during each week chemotherapy is given . RESULTS 104 patients were r and omized into group A and 103 into group B. There was no statistically significant difference in either disease-free survival or overall survival between the two groups . Toxicity was also the same , except for the flu-like syndrome associated with the IFN-alpha administration . CONCLUSIONS There was no difference in efficacy between the two combinations . Toxicity was greater with the LV + 5-FU + IFN-alpha regimen because of the flu-like syndrome Fifty-three patients with colorectal cancer Dukes ' B2 and C were r and omized after surgery . One group was treated by radio- and /or chemotherapy and the second by radio- and /or chemotherapy and MER . After 24 and 36 months a significant longer disease free interval , lower recurrence rate and better survival was found in the group treated by radio-chemo- and immunotherapy . Treatment was well tolerated and there were few local side effects from the MER injections . The long time efficacy of this adjuvant treatment whether it increases the cure rate or only delays recurrence does require longer follow-up Adjuvant therapy was given to patients with colorectal cancer stage Duke 's B2 and C. The 53 patients were r and omized and stratified after surgery . One arm received radiotherapy and chemotherapy and the other radiotherapy , chemotherapy , and MER . The survival and disease-free interval up to 2 years were longer and better in the radiochemo-MER arm . It is too early to conclude whether this combination increases the cure rate or delays the appearance of metastases . The time interval between the cytotoxic therapy  and the immunotherapy and the dose of the immunotherapeutic agent is very important for the success of the combination therapy . Further follow-up is necessary and more patients need to be entered into the trial BACKGROUND Preoperative radiotherapy is recommended for selected patients with rectal cancer . We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer . METHODS We r and omly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy , preoperative chemoradiotherapy , preoperative radiotherapy and postoperative chemotherapy , or preoperative chemoradiotherapy and postoperative chemotherapy . Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks . One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day , both given for 5 days . Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy ; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy . The primary end point was overall survival . RESULTS We enrolled 1011 patients in the trial . There was no significant difference in overall survival between the groups that received chemotherapy preoperatively ( P=0.84 ) and those that received it postoperatively ( P=0.12 ) . The combined 5-year overall survival rate for all four groups was 65.2 % . The 5-year cumulative incidence rates for local recurrences were 8.7 % , 9.6 % , and 7.6 % in the groups that received chemotherapy preoperatively , postoperatively , or both , respectively , and 17.1 % in the group that did not receive chemotherapy ( P=0.002 ) . The rate of adherence to preoperative chemotherapy was 82.0 % , and to postoperative chemotherapy was 42.9 % . CONCLUSIONS In patients with rectal cancer who receive  preoperative radiotherapy , adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival . Chemotherapy , regardless of whether it is administered before or after surgery , confers a significant benefit with respect to local control . ( Clinical Trials.gov number , NCT00002523 [ Clinical Trials.gov ] . ) The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil ( 5-FU ) was predictive for survival among patients with locally advanced rectal cancer .  Preoperative chemoradiation ( CTX/XRT ) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU ( 300 mg/m2/day ) was given to 117 patients . The pretreatment stage distribution , as determined by endorectal ultrasound ( u ) , included uT2N0 in 2 % , uT3N0 in 47 % , uT3N1 in 49 % , and uT4N0 in 2 % of cases ; endorectal ultrasound was not performed in 13 % of cases ( 15 patients ) . Approximately 6 weeks after completion of CTX/XRT , surgery was performed . Adjuvant chemotherapy , consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 leucovorin for 5 days , was administered every 28 days for 4 to 6 cycles after surgical resection . Among the 74 patients treated with adjuvant chemotherapy , the preoperative stage of disease was 31 with T3N0 and 43 T3N1 . Median follow-up was 46 months ( range 2 to 89 months ) . The pathologic tumor stages were Tis-2N0 in 26 % , T2N1 in 5 % , T3N0 in 21 % , T3N1 in 15 % , T4N0 in 5 % , and T4N1 in 1 % ; a complete response ( CR ) to preoperative CTX/XRT was pathologically confirmed in 32 ( 27 % ) of patients . Tumor down-staging occurred in 72 ( 62 % ) cases . A sphincter-saving procedure ( SP ) was possible in 59 % of patients . The median DFS and overall survival rates for responders were 46 months and 47 months , respectively ; for non-responders these outcome measures were 38 months and 41 months , respectively . Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT ( p < 0.00001 ) , CR to CTX/XRT ( p < 0.009 ) and SP ( p < 0.012 ) . Likewise , these parameters also significantly influenced DFS rates ( CTX/XRT p < 0.00001 ; CR p < 0.006 ; and SP p < 0.008 ) . Control of pelvic disease was influenced by clinical size ( p < 0.002 ) and SP ( p < 0.016 ) on univariate analysis . On multivariate analysis only clinical size ( p < 0.002 ) continued to be a significant factor for local control . Factors on multivariate analysis that result ed in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT ( p < 0.017 ) and administration of adjuvant chemotherapy ( p < 0.034 ) . Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates . Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in overall survival among patients with locally advanced rectal cancer . Patients who fail to respond to preoperative 5-FU based chemotherapy given concomitantly with radiation have higher rates of distant metastases with adjuvant 5-FU therapy BACKGROUND / AIMS The usefulness of adjuvant chemotherapy started immediately following surgery was evaluated . METHODOLOGY A r and omized clinical trial was performed on 133 patients with advanced colorectal cancer using oral anticancer agents with one-week continuous 5-FU infusion starting immediately after curative surgery . In Group A and Group B , 300 mg/day of HCFU was orally administered for two years starting two weeks after surgery , and in addition , 333 mg/m2/day of 5-FU was drip infused from the central vein for seven days from the day of surgery in Group B. RESULTS For 1919 days after surgery , there were no significant intergroup differences in overall survival ( OS ) and disease-free survival ( DFS ) , but OS and DFS in Group B rectal cancer patients were significantly better when compared to Group A rectal cancer patients . On the other h and , OS tended to be better in Group A colon cancer patients , but no significant intergroup differences were seen , while intergroup differences tended to be smaller when corrected for disease stage . CONCLUSIONS Continuous 5-FU infusion starting immediately after curative surgery for colorectal cancer was safe . While further investigation is necessary to eluci date the degree of improvement in postoperative prognosis , the results of the present study suggest that continuous 5-FU infusion improves prognosis in advanced rectal cancer BACKGROUND Short-term preoperative radiotherapy and total mesorectal excision have each been shown to improve local control of disease in patients with resectable rectal cancer . We conducted a multicenter , r and omized trial to determine whether the addition of preoperative radiotherapy increases the benefit of total mesorectal excision . METHODS We r and omly assigned 1861 patients with resectable rectal cancer either to preoperative radiotherapy  ( 5 Gy on each of five days )  followed by total mesorectal excision ( 924 patients ) or to total mesorectal excision alone ( 937 patients ) . The trial was conducted with the use of st and ardization and quality -control measures to ensure the consistency of the radiotherapy , surgery , and pathological techniques . RESULTS Of the 1861 patients r and omly assigned to one of the two treatment groups , 1805 were eligible to participate . The overall rate of survival at two years among the eligible patients was 82.0 percent in the group assigned to both radiotherapy and surgery and 81.8 percent in the group assigned to surgery alone ( P=0.84 ) . Among the 1748 patients who underwent a macroscopically complete local resection , the rate of local recurrence at two years was 5.3 percent . The rate of local recurrence at two years was 2.4 percent in the radiotherapy-plus-surgery group and 8.2 percent in the surgery-only group ( P<0.001 ) . CONCLUSIONS Short-term preoperative radiotherapy reduces the risk of local recurrence in patients with rectal cancer who undergo a st and ardized total mesorectal excision PURPOSE The gastrointestinal Intergroup studied postoperative adjuvant chemotherapy and radiation therapy in patients with T3/4 and N+ rectal cancer after potentially curative surgery to try to improve chemotherapy and to determine the risk of systemic and local failure . PATIENTS AND METHODS All patients had a potentially curative surgical resection and were treated with two cycles of chemotherapy followed by chemoradiation therapy and two additional cycles of chemotherapy . Chemotherapy regimens were bolus fluorouracil ( 5-FU ) , 5-FU and leucovorin , 5-FU and levamisole , and 5-FU , leucovorin , and levamisole . Pelvic irradiation was given to a dose of 45 Gy to the whole pelvis and a boost to 50.4 to 54 Gy . RESULTS One thous and six hundred ninety-five patients were entered and fully assessable , with a median follow-up of 7.4 years . There was no difference in overall survival ( OS ) or disease-free survival ( DFS ) by drug regimen . DFS and OS decreased between years 5 and 7 ( from 54 % to 50 % and 64 % to 56 % , respectively ) , although recurrence-free rates had only a small decrease . The local recurrence rate was 14 % ( 9 % in low-risk [ T1 to N2 + ] and 18 % in high-risk patients [ T3N+ , T4N ] ) . Overall , 7-year survival rates were 70 % and 45 % for the low-risk and high-risk groups , respectively . Males had a poorer overall survival rate than females . CONCLUSION There is no advantage to leucovorin- or levamisole-containing regimens over bolus 5-FU alone in the adjuvant treatment of rectal cancer when combined with irradiation . Local and distant recurrence rates are still high , especially in T3N+ and T4 patients , even with full adjuvant chemoradiation therapy Purpose After neoadjuvant radiochemotherapy and surgery , there is no general agreement about whether postoperative chemotherapy is necessary . With the help of clinical and pathohistologic data , prognostic factors were determined as a basis for the decision to spare a patient additional chemotherapy or to urgently recommend it . Results Ninety-five patients treated with neoadjuvant 5-fluorouracil-based radiochemotherapy ( November 4 , 1997 and June 15 , 2004 ) without distant metastases and an R0 ( microscopically complete ) resection were evaluated .  Adjuvant chemotherapy ( 5-fluorouracil or 5-fluorouracil/folinic acid ) was given to 65 of 95 patients ( 68.4 percent ) . The disease-free survival rate after 36 months was chosen as the target parameter ( median follow-up , 36 months ) . Methods The five-year survival rate for all patients was 80.3 ± 5.6 percent ; the five-year disease-free survival was 78.1 ± 5.1 percent ; the five-year local control rate was 94.2 ± 5.1 percent . In the univariate and multivariate analysis of the disease-free survival , the pathohistologic lymph node status after radiochemotherapy ( ypN ) was the only significant prognostic parameter . Disease-free survival ( 36 months ) for patients without lymph node metastases ( ypN0 ) was excellent , independent of whether they had received postoperative chemotherapy ( n = 43 ; 87.5 ± 6.0 percent ) or not ( n = 29 ; 87.7 ± 6.7 percent ) . Patients with ypN2 status have , despite chemotherapy , a poor disease-free survival at 30 ± 17.6 percent after 36 months . Conclusions These retrospective data suggest that , for some patients , postoperative chemotherapy can be spared . For patients with ypN2 status , an intensification of the postoperative chemotherapy should be considered . Further evaluation in prospect i ve studies is urgently recommended BACKGROUND Although adjuvant radiotherapy was proved to be effective for local control of rectal cancer even after st and ardized mesorectal excision , the role of adjuvant chemotherapy after such st and ardized surgery remains to be clarified . We aim ed to assess the efficacy of a combination of uracil and tegafur for pathological stage III rectal cancer treated by st and ardized mesorectal excision with selective lateral pelvic lymphadenectomy . METHODS We r and omly assigned patients with completely resected stage III rectal cancer , who underwent st and ardized mesorectal excision with selective lateral pelvic lymphadenectomy , to receive either oral uracil-tegafur ( 400 mg/m2 tegafur per day ) for one year or no treatment . St and ardization and quality control of the surgery and pathological techniques were ensured by use of the guidelines of the Japanese Society for Cancer of the Colon and Rectum . The primary endpoint was relapse-free survival . The secondary endpoint was overall survival . RESULTS We enrolled and r and omized 276 patients . Excluding two ineligible patients , 274 were included in the analysis . Planned interim analysis 2 years after accrual termination revealed significant prolongation of relapse-free survival ( P = 0.001 ) and overall survival ( P = 0.005 ) in the uracil-tegafur group . The 3-year relapse-free survival and overall survival rates were 78 and 91 % in the chemotherapy group and 60 and 81 % in the surgery-alone group , respectively . Local recurrence rates were low in both groups . Grade 3 events occurred in 17 % of the chemotherapy patients , but no grade 4 or more events occurred . CONCLUSION Adjuvant chemotherapy with uracil-tegafur improves survival of patients with stage III rectal cancer after st and ardized mesorectal excision with selective lateral pelvic lymphadenectomy 366 patients fully resected from a Dukes B2 or C colorectal cancer were r and omised to receive 6 courses of  systemic chemotherapy comprising either 5-fluorouracil ( 5 FU ) alone ( arm A : 450 mg/m2/day-5/21 days ) or combined folinic acid ( FOL ) and 5 FU ( arm B : respectively 200 mg/m2 racemic form or 100 mg/m2-l-form and 370 mg/m2/day-5/21 days ) . 173 patients had also been initially r and omised to receive one course of intraportal chemotherapy just after surgery or no portal treatment . Oral levamisole ( 150 mg/day ; 3 days every other week ) was given to all patients for one year . A significantly higher incidence of leuco-granulocytopenia was observed in the arm A ( 5 FU alone ) inducing more frequent dose delays and adaptations as well as levamisole 's withdrawal . Then dose-intensities and dose-intensity products were lower in this arm but the dose intensity expressed in mg/m2/week remained higher ( 631 + /- 107 vs 557 + /- 99 ; p < 0.001 ) . The median follow-up in the study was 4.5 years . Relapse free ( RFS ) and overall survivals ( OAS ) were prolonged in the 5 FU alone group peculiarly in those patients who had not been r and omised for portal treatment . Curves diverged progressively with longer follows-up ( at 8 years ; RFS in arm A : 67 - 71 % vs 59 - 53 % in arm B ; OAS in arm A : 72 - 74 % vs 56 - 46 % in arm B ) . Patients suffering from a colon or a Dukes C cancer benefited the most from the treatment with 5 FU alone . The results are discussed in the light of other recent adjuvant trials . Well dosed 5 FU over a short period of time without folinic acid may be a valuable and inexpensive adjuvant treatment for colorectal cancer . Levamisole may no longer be recommended in this setting BACKGROUND Adjuvant radiotherapy for rectal cancer has been extensively studied , but no trial has unequivocally demonstrated improved overall survival with radiotherapy , despite a reduction in the rate of local recurrence . METHODS Between March 1987 and February 1990 , we r and omly assigned 1168 patients younger than 80 years of age who had resectable rectal cancer to undergo preoperative irradiation ( 25 Gy delivered in five fractions in one week ) followed by surgery within one week or to have surgery alone .  RESULTS The irradiation did not increase postoperative mortality . After five years of follow-up , the rate of local recurrence was 11 percent ( 63 of 553 patients ) in the group that received radiotherapy before surgery and 27 percent ( 150 of 557 ) in the group treated with surgery alone ( P<0.001 ) . This difference was found in all subgroups defined according to Dukes ' stage . The overall five-year survival rate was 58 percent in the radiotherapy-plus-surgery group and 48 percent in the surgery-alone group ( P=0.004 ) . The cancer-specific survival rates at nine years among patients treated with curative resection were 74 percent and 65 percent , respectively ( P=0.002 ) . CONCLUSIONS A short-term regimen of high-dose preoperative radiotherapy reduces rates of local recurrence and improves survival among patients with resectable rectal cancer PURPOSE Capecitabine is an attractive radiosensitizer which can be tumor specific . This study was undertaken to evaluate the toxicity and efficacy of oral capecitabine when used with preoperative radiation therapy . METHODS AND MATERIAL S We conducted a prospect i ve Phase II trial to assess the pathologic response , sphincter preservation effect , and acute toxicity of preoperative chemoradiation ( CRT ) in locally advanced ( uT3 - 4/N + ) but resectable adenocarcinoma of the lower two-thirds of the rectum . The radiation dose was 50 Gy over 5 weeks ( 46 Gy to whole pelvis + 4 Gy boost ) , and capecitabine was administered daily at a dose of 1650 mg/m(2 ) during the entire course of radiation therapy . Surgery was performed with st and ardized total mesorectal excision 4 to 6 weeks after completion of CRT and followed by four cycles of capecitabine ( 2500 mg/m(2)/day for 14 days ) . RESULTS Ninety-five patients were entered into this study ; their median age was 55 ( range , 31 - 75 years ) . Ninety ( 95 % ) patients completed preoperative CRT as planned , and complete resection was achieved in 92 of 94 resected cases ( 98 % ) . Downstaging rate was 71 % ( 56/79 ) on endorectal ultrasonography , and it was 76 % ( 71/94 ) on pathology finding . No tumor cell was observed in the specimens of 11 patients ( 12 % ) . Among the 54 whose tumor was located within 5 cm from the anal verge , 40 patients ( 74 % ) underwent sphincter-preserving procedures . Elevation of the distal tumor margin from the anal verge by preoperative CRT was 0.8 + /- 1.3 cm . Grade 3 toxicities were rare ( diarrhea in 3 % and neutropenia in 1 % ) . CONCLUSION Preoperative CRT using capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation with a low toxicity profile
BACKGROUND Colorectal cancer is one of the most common types of cancer in the Western world .
Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative ( i.e. , adjuvant ) chemotherapy with 5-fluorouracil ( 5-FU ) based regimens is now the st and ard treatment in Dukes ' C ( TNM stage III ) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases .
In contrast , the evidence for recommendations of adjuvant therapy in rectal cancer is sparse .
In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative ( i.e. , neoadjuvant ) downstaging by radiotherapy ( or chemoradiotion ) , whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes ' C rectal cancers .
Overall , no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma ; moreover , no formal systematic review and meta- analysis has been so far performed on this subject .
OBJECTIVES We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer .
Cancer or carcinom * or adenocarc * or neoplasm * or tumour - 3 .
Adjuv * - 4 .
Chemother * - 5 .