human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE The first planned interim analysis ( median follow-up , 3 years ) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival , the primary end point . The results were therefore opened at the recommendation of an independent data and safety monitoring committee . We report 5-year follow-up data on patients enrolled onto the ACTS-GC study . PATIENTS AND METHODS Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were r and omly assigned to receive S-1 after surgery or surgery only . S-1 ( 80 to 120 mg per day ) was given for 4 weeks , followed by 2 weeks of rest . This 6-week cycle was repeated for 1 year . The primary end point was overall survival , and the secondary end points were relapse-free survival and safety . RESULTS The overall survival rate at 5 years was 71.7 % in the S-1 group and 61.1 % in the surgery-only group ( hazard ratio [ HR ] , 0.669 ; 95 % CI , 0.540 to 0.828 ) . The relapse-free survival rate at 5 years was 65.4 % in the S-1 group and 53.1 % in the surgery-only group ( HR , 0.653 ; 95 % CI , 0.537 to 0.793 ) . Subgroup analyses according to principal demographic factors such as sex , age , disease stage , and histologic type showed no interaction between treatment and any characteristic . CONCLUSION On the basis of 5-year follow-up data , postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy BACKGROUND The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy . We did the Stomach cancer Adjuvant Multi-Institutional group Trial ( SAMIT ) to assess the superiority of sequential treatment ( paclitaxel then tegafur and uracil [ UFT ] or paclitaxel then S-1 ) compared with monotherapy ( UFT or S-1 ) and also the non-inferiority of UFT compared with S-1 . METHODS We did this r and omised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan . We enrolled patients aged 20 - 80 years with T4a or T4b gastric cancer , who had had D2 dissection and a ECOG performance score of 0 - 1 . Patients were r and omly assigned to one of four treatment groups with minimisation for tumour size , lymph node metastasis , and study site . Patients received UFT only ( 267 mg/m(2 ) per day ) , S-1 only ( 80 mg/m(2 ) per day ) for 14 days , with a 7-day rest period or three courses of intermittent weekly paclitaxel ( 80 mg/m(2 ) ) followed by either UFT , or S-1 . Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups . The primary endpoint was disease-free survival assessed by intention to treat . We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33 . This trial was registered at UMIN Clinical Trials Registry , number C000000082 . FINDINGS We r and omly assigned 1495 patients between Aug 3 , 2004 , and Sept 29 , 2009 . 374 patients were assigned to receive UFT alone , 374 to receive S-1 alone , 374 to received paclitaxel then UFT , and 373 to receive paclitaxel then S-1 . We included 1433 patients in the primary analysis after at least 3 years of follow-up ( 359 , 364 , 355 , and 355 in each group respectively ) . Protocol treatment was completed by 215 ( 60 % ) patients in the UFT group , 224 ( 62 % ) in the S-1 group , 242 ( 68 % ) in the paclitaxel then UFT group , and 250 ( 70 % ) in the paclitaxel then S-1  group . 3-year disease-free survival for monotherapy was 54·0 % ( 95 % CI 50·2 - 57·6 ) and that of sequential treatment was 57·2 % ( 53·4 - 60·8 ; hazard ratio [ HR ] 0·92 , 95 % CI 0·80 - 1·07 , p=0·273 ) . 3-year disease-free survival for the UFT group was 53·0 % ( 95 % CI 49·2 - 56·6 ) and that of the S-1 group was 58·2 % ( 54·4 - 61·8 ; HR 0·81 , 95 % CI 0·70 - 0·93 , p=0·0048 ; pnon-inferiority=0·151 ) . The most common grade 3 - 4 haematological adverse event was neutropenia ( 41 [ 11 % ] of 359 patients in the UFT group , 48 [ 13 % ] of 363 in the S-1 group , 46 [ 13 % ] of 355 in the paclitaxel then UFT group , and 83 [ 23 % ] of 356 in the paclitaxel then S-1  group ) . The most common grade 3 - 4 non-haematological adverse event was anorexia ( 21 [ 6 % ] , 24 [ 7 % ] , seven [ 2 % ] , and 18 [ 5 % ] , respectively ) . INTERPRETATION Sequential treatment did not improve disease-free survival , and UFT was not non-inferior to S-1 ( and S-1 was superior to UFT ) , therefore S-1 monotherapy should remain the st and ard treatment for locally advanced gastric cancer in Japan . FUNDING Epidemiological and Clinical Research Information Network Background : Despite the small but significant survival benefit of adjuvant chemotherapy in locally advanced gastric cancer ( LAGC ) , the optimal regimen remains to be determined . We conducted a r and omized trial comparing oral ( PO ) chemoimmunotherapy ( CITX ) with intravenous ( IV ) CITX in LAGC patients ( stages IB-IIIB ) with curative resection ( ≥ D2 dissection ) . Methods : The patients were r and omized to the IV ( 5-fluorouracil 500 mg/m2 weekly for 24 weeks , mitomycin-C 8 mg/m2 every 6 weeks × 4 ) or the PO ( uracil-ftorafur ( UFT ) 400 - 600 mg/day for 12 months ) group . Patients in both groups received PO polysaccharide-K ( 3 g/day for 4 months ) . The planned number of patients was 368 for proving the non-inferiority of PO CITX compared to IV CITX for overall survival . Results : The trial was closed prematurely after enrolling 82 patients ( 44 in the IV group , 38 in the PO group ) . With a median follow-up of 82 months , there were no significant differences in the 5-year disease-free survival ( 73 % vs. 55 % , p = 0.358 ) and overall survival ( 77 % vs. 66 % , p = 0.159 ) between the 2 groups . The IV group demonstrated a higher incidence of grade 2 or 3 neutropenia , thrombocytopenia , and vomiting . Conclusions : PO CITX with UFT appeared to be at least non-inferior to 5-fluorouracil and mitomycin-C CITX , with lower toxicity in the adjuvant treatment for LAGC BACKGROUND To investigate the efficacy and toxicity of FOLFOX4 regimen and LV5Fu2 regimen in patients with advanced gastric adenocarcinoma after curative gastrectomy . METHODS Eighty patients with gastric adenocarcinoma after curative gastrectomy were r and omized to receive a 2-h infusion of leucovorin ( LV ; 200mg/m(2)/d ) followed by a 5-fluorouracil ( 5-FU ) bolus ( 400mg/m(2)/d ) and 22-h infusion ( 600 mg/m(2)/d ) for 2 consecutive days every 2 weeks , either alone or together with oxaliplatin 85 mg/m(2 ) as a 2-h infusion on day 1 ( FOLFOX4 regimen or LV5Fu2 regimen ) . The observation points were recurrence free survival , overall survival and toxicity of the two groups . RESULTS All patients had received curative gastrectomy ( R0 resection ) before received either of the two regimens . The 3-year recurrence free survival rate and the 3-year overall survival rate in FOLFOX4 group were all significantly better than those in the control group ( median , 30.0 months vs. 16.0 months , P<0.05 ; 36.0 months vs. 28.0 months , P<0.05 ) . COX multivariant analysis was used to evaluate the prognostic factors and oxaliplatin was found to be the independent prognostic factor and could improve the survival rate in FOLFOX4 group . Grade 3/4 peripheral neuropathy occurred in 19 % in FOLFOX4 group . There was no significant difference between the two groups in neutropenia , leukopenia , anemia , gastrointestinal reaction and so on . Three patients in each group were lost to follow up during treatment . CONCLUSION FOLFOX4 regimen showed good efficacy and an acceptable safety profile for patients with advanced gastric adenocarcinoma after curative gastrectomy compared with the control group . It may prove to be a suitable alterative regimen in this indication BACKGROUND Promising findings obtained using a weekly regimen of 5-fluorouracil ( 5-FU ) , epidoxorubicin , leucovorin ( LV ) , and cisplatin ( PELFw ) to treat locally advanced and metastatic gastric cancer prompted the Italian Group for the Study of Digestive Tract Cancer ( GISCAD ) to investigate the efficacy of this regimen as adjuvant treatment for high-risk radically resected gastric cancer patients . METHODS From January 1998 to January 2003 , 400 gastric cancer patients at high risk for recurrence including patients with serosal invasion ( stage pT3 N0 ) and /or lymph node metastasis ( stage pT2 or pT3 N1 , N2 , or N3 ) , were enrolled in a trial of adjuvant chemotherapies ; 201 patients were r and omly assigned to receive the  PELFw regimen , consisting of eight weekly administrations of cisplatin ( 40 mg/m2 ) , LV ( 250 mg/m2 ) , epidoxorubicin ( 35 mg/m2 ) , 5-FU ( 500 mg/m2 ) , and glutathione ( 1.5 g/m2 ) with the support of filgrastim , and 196 patients were assigned to a regimen consisting of six monthly administrations of a 5-day course of 5-FU ( 375 mg/m2 daily ) and LV ( 20 mg/m2 daily , 5-FU/LV ) . Disease-free and overall survival were estimated and compared between arms using hazard ratios ( HRs ) and Kaplan-Meier estimates . All statistical tests were two-sided . RESULTS The 5-year survival rates were 52 % in the PELFw arm and 50 % in the 5-FU/LV arm . Compared with the 5-FU/LV regimen , the PELFw regimen did not reduce the risk of death ( HR = 0.95 , 95 % confidence interval [ CI ] = 0.70 to 1.29 ) or relapse ( HR = 0.98 , 95 % CI = 0.75 to 1.29 ) . Less than 10 % of patients in either arm experienced a grade 3 or 4 toxic episode . Neutropenia ( occurring more often in the PELFw arm ) and diarrhea and mucositis ( more prevalent in the 5-FU/LV arm ) were the most common serious side effects . Nevertheless , only 19 patients ( 9.4 % ) completed the treatment in the PELFw arm and 85 ( 43 % ) patients completed the treatment in the 5-FU/LV arm . CONCLUSIONS Our study found no benefit from an intensive weekly chemotherapy in gastric cancer . The extent of toxicity experienced by the patients in the adjuvant setting suggests that , in gastric cancer , chemotherapy may be more safely administered preoperatively BACKGROUND Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated . In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer ( SPIRITS ) trial , we aim ed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE The first planned interim analysis ( median follow-up , 3 years ) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival , the primary end point . The results were therefore opened at the recommendation of an independent data and safety monitoring committee . We report 5-year follow-up data on patients enrolled onto the ACTS-GC study . PATIENTS AND METHODS Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were r and omly assigned to receive S-1 after surgery or surgery only . S-1 ( 80 to 120 mg per day ) was given for 4 weeks , followed by 2 weeks of rest . This 6-week cycle was repeated for 1 year . The primary end point was overall survival , and the secondary end points were relapse-free survival and safety . RESULTS The overall survival rate at 5 years was 71.7 % in the S-1 group and 61.1 % in the surgery-only group ( hazard ratio [ HR ] , 0.669 ; 95 % CI , 0.540 to 0.828 ) . The relapse-free survival rate at 5 years was 65.4 % in the S-1 group and 53.1 % in the surgery-only group ( HR , 0.653 ; 95 % CI , 0.537 to 0.793 ) . Subgroup analyses according to principal demographic factors such as sex , age , disease stage , and histologic type showed no interaction between treatment and any characteristic . CONCLUSION On the basis of 5-year follow-up data , postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy BACKGROUND The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy . We did the Stomach cancer Adjuvant Multi-Institutional group Trial ( SAMIT ) to assess the superiority of sequential treatment ( paclitaxel then tegafur and uracil [ UFT ] or paclitaxel then S-1 ) compared with monotherapy ( UFT or S-1 ) and also the non-inferiority of UFT compared with S-1 . METHODS We did this r and omised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan . We enrolled patients aged 20 - 80 years with T4a or T4b gastric cancer , who had had D2 dissection and a ECOG performance score of 0 - 1 . Patients were r and omly assigned to one of four treatment groups with minimisation for tumour size , lymph node metastasis , and study site . Patients received UFT only ( 267 mg/m(2 ) per day ) , S-1 only ( 80 mg/m(2 ) per day ) for 14 days , with a 7-day rest period or three courses of intermittent weekly paclitaxel ( 80 mg/m(2 ) ) followed by either UFT , or S-1 . Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups . The primary endpoint was disease-free survival assessed by intention to treat . We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33 . This trial was registered at UMIN Clinical Trials Registry , number C000000082 . FINDINGS We r and omly assigned 1495 patients between Aug 3 , 2004 , and Sept 29 , 2009 . 374 patients were assigned to receive UFT alone , 374 to receive S-1 alone , 374 to received paclitaxel then UFT , and 373 to receive paclitaxel then S-1 . We included 1433 patients in the primary analysis after at least 3 years of follow-up ( 359 , 364 , 355 , and 355 in each group respectively ) . Protocol treatment was completed by 215 ( 60 % ) patients in the UFT group , 224 ( 62 % ) in the S-1 group , 242 ( 68 % ) in the paclitaxel then UFT group , and 250 ( 70 % ) in the paclitaxel then S-1  group . 3-year disease-free survival for monotherapy was 54·0 % ( 95 % CI 50·2 - 57·6 ) and that of sequential treatment was 57·2 % ( 53·4 - 60·8 ; hazard ratio [ HR ] 0·92 , 95 % CI 0·80 - 1·07 , p=0·273 ) . 3-year disease-free survival for the UFT group was 53·0 % ( 95 % CI 49·2 - 56·6 ) and that of the S-1 group was 58·2 % ( 54·4 - 61·8 ; HR 0·81 , 95 % CI 0·70 - 0·93 , p=0·0048 ; pnon-inferiority=0·151 ) . The most common grade 3 - 4 haematological adverse event was neutropenia ( 41 [ 11 % ] of 359 patients in the UFT group , 48 [ 13 % ] of 363 in the S-1 group , 46 [ 13 % ] of 355 in the paclitaxel then UFT group , and 83 [ 23 % ] of 356 in the paclitaxel then S-1  group ) . The most common grade 3 - 4 non-haematological adverse event was anorexia ( 21 [ 6 % ] , 24 [ 7 % ] , seven [ 2 % ] , and 18 [ 5 % ] , respectively ) . INTERPRETATION Sequential treatment did not improve disease-free survival , and UFT was not non-inferior to S-1 ( and S-1 was superior to UFT ) , therefore S-1 monotherapy should remain the st and ard treatment for locally advanced gastric cancer in Japan . FUNDING Epidemiological and Clinical Research Information Network Background : Despite the small but significant survival benefit of adjuvant chemotherapy in locally advanced gastric cancer ( LAGC ) , the optimal regimen remains to be determined . We conducted a r and omized trial comparing oral ( PO ) chemoimmunotherapy ( CITX ) with intravenous ( IV ) CITX in LAGC patients ( stages IB-IIIB ) with curative resection ( ≥ D2 dissection ) . Methods : The patients were r and omized to the IV ( 5-fluorouracil 500 mg/m2 weekly for 24 weeks , mitomycin-C 8 mg/m2 every 6 weeks × 4 ) or the PO ( uracil-ftorafur ( UFT ) 400 - 600 mg/day for 12 months ) group . Patients in both groups received PO polysaccharide-K ( 3 g/day for 4 months ) . The planned number of patients was 368 for proving the non-inferiority of PO CITX compared to IV CITX for overall survival . Results : The trial was closed prematurely after enrolling 82 patients ( 44 in the IV group , 38 in the PO group ) . With a median follow-up of 82 months , there were no significant differences in the 5-year disease-free survival ( 73 % vs. 55 % , p = 0.358 ) and overall survival ( 77 % vs. 66 % , p = 0.159 ) between the 2 groups . The IV group demonstrated a higher incidence of grade 2 or 3 neutropenia , thrombocytopenia , and vomiting . Conclusions : PO CITX with UFT appeared to be at least non-inferior to 5-fluorouracil and mitomycin-C CITX , with lower toxicity in the adjuvant treatment for LAGC BACKGROUND To investigate the efficacy and toxicity of FOLFOX4 regimen and LV5Fu2 regimen in patients with advanced gastric adenocarcinoma after curative gastrectomy . METHODS Eighty patients with gastric adenocarcinoma after curative gastrectomy were r and omized to receive a 2-h infusion of leucovorin ( LV ; 200mg/m(2)/d ) followed by a 5-fluorouracil ( 5-FU ) bolus ( 400mg/m(2)/d ) and 22-h infusion ( 600 mg/m(2)/d ) for 2 consecutive days every 2 weeks , either alone or together with oxaliplatin 85 mg/m(2 ) as a 2-h infusion on day 1 ( FOLFOX4 regimen or LV5Fu2 regimen ) . The observation points were recurrence free survival , overall survival and toxicity of the two groups . RESULTS All patients had received curative gastrectomy ( R0 resection ) before received either of the two regimens . The 3-year recurrence free survival rate and the 3-year overall survival rate in FOLFOX4 group were all significantly better than those in the control group ( median , 30.0 months vs. 16.0 months , P<0.05 ; 36.0 months vs. 28.0 months , P<0.05 ) . COX multivariant analysis was used to evaluate the prognostic factors and oxaliplatin was found to be the independent prognostic factor and could improve the survival rate in FOLFOX4 group . Grade 3/4 peripheral neuropathy occurred in 19 % in FOLFOX4 group . There was no significant difference between the two groups in neutropenia , leukopenia , anemia , gastrointestinal reaction and so on . Three patients in each group were lost to follow up during treatment . CONCLUSION FOLFOX4 regimen showed good efficacy and an acceptable safety profile for patients with advanced gastric adenocarcinoma after curative gastrectomy compared with the control group . It may prove to be a suitable alterative regimen in this indication BACKGROUND Promising findings obtained using a weekly regimen of 5-fluorouracil ( 5-FU ) , epidoxorubicin , leucovorin ( LV ) , and cisplatin ( PELFw ) to treat locally advanced and metastatic gastric cancer prompted the Italian Group for the Study of Digestive Tract Cancer ( GISCAD ) to investigate the efficacy of this regimen as adjuvant treatment for high-risk radically resected gastric cancer patients . METHODS From January 1998 to January 2003 , 400 gastric cancer patients at high risk for recurrence including patients with serosal invasion ( stage pT3 N0 ) and /or lymph node metastasis ( stage pT2 or pT3 N1 , N2 , or N3 ) , were enrolled in a trial of adjuvant chemotherapies ; 201 patients were r and omly assigned to receive the  PELFw regimen , consisting of eight weekly administrations of cisplatin ( 40 mg/m2 ) , LV ( 250 mg/m2 ) , epidoxorubicin ( 35 mg/m2 ) , 5-FU ( 500 mg/m2 ) , and glutathione ( 1.5 g/m2 ) with the support of filgrastim , and 196 patients were assigned to a regimen consisting of six monthly administrations of a 5-day course of 5-FU ( 375 mg/m2 daily ) and LV ( 20 mg/m2 daily , 5-FU/LV ) . Disease-free and overall survival were estimated and compared between arms using hazard ratios ( HRs ) and Kaplan-Meier estimates . All statistical tests were two-sided . RESULTS The 5-year survival rates were 52 % in the PELFw arm and 50 % in the 5-FU/LV arm . Compared with the 5-FU/LV regimen , the PELFw regimen did not reduce the risk of death ( HR = 0.95 , 95 % confidence interval [ CI ] = 0.70 to 1.29 ) or relapse ( HR = 0.98 , 95 % CI = 0.75 to 1.29 ) . Less than 10 % of patients in either arm experienced a grade 3 or 4 toxic episode . Neutropenia ( occurring more often in the PELFw arm ) and diarrhea and mucositis ( more prevalent in the 5-FU/LV arm ) were the most common serious side effects . Nevertheless , only 19 patients ( 9.4 % ) completed the treatment in the PELFw arm and 85 ( 43 % ) patients completed the treatment in the 5-FU/LV arm . CONCLUSIONS Our study found no benefit from an intensive weekly chemotherapy in gastric cancer . The extent of toxicity experienced by the patients in the adjuvant setting suggests that , in gastric cancer , chemotherapy may be more safely administered preoperatively BACKGROUND Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated . In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer ( SPIRITS ) trial , we aim ed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 
    Output:
    