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: UNLABELLED Various chemotherapies have been used to treat inoperable gastric cancer . Most combination therapies include cisplatin ( CDDP ) and fluoropyrimidine ( 5-FUs ) , which are thought of as key drugs . In the present study , we r and omly compared mitomycin ( MMC ) and CDDP plus doxifluridine ( 5'-DFUR ) , which is an oral 5-FU and an intermediate metabolite of capecitabine ( Xeloda ) , with CDDP plus 5'-DFUR in advanced unresectable gastric cancer . Regimen A was CDDP ( 70 mg/m2 , by 2-hour intravenous drip infusion on day 1 ) , MMC ( 7 mg/m2 , injected intravenously on day 2 ) , and oral 5'-DFUR ( 1200 mg/m2 , on days 4 to 7 , 11 to 14 , 18 to 21 and 25 to 28 ; 3 days rest and 4 days administration ) . Regimen B was identical to regimen A without MMC . RESULTS The response rate was 25.0 % ( 8/32 patients ) in Regimen A , 17.2 % ( 5/29 ) in Regimen B ( p=0.541 ) . The median survival time was 241 days in Regimen A and 179 days in Regimen B ( p=0.498 ) . In Regimen A , although no significant difference was observed , end points such as response rate and suvival improved . Thus , we concluded that a r and omized controlled phase III study with more subjects should be conducted BACKGROUND Irinotecan , in combination with 5-fluorouracil ( 5-FU ) or cisplatin , has demonstrated efficacy against advanced gastric cancer ( AGC ) . PATIENTS AND METHODS Chemotherapy-naive AGC patients were r and omly assigned to receive irinotecan 150 mg/m(2 ) on day 1 , leucovorin 20 mg/m(2 ) and a 22-h infusion of 5-FU 1000 mg/m(2 ) on days 1 and 2 ( ILF ) or ILF plus cisplatin 30 mg/m(2 ) on day 2 ( PILF ) . Treatment was repeated every 2 weeks . RESULTS Of 91 registered patients , 45 patients were treated with ILF and 45 with PILF .  For both arms , 687 chemotherapy cycles were delivered ( median = 7 for ILF and 8 for PILF ) . Both ILF and PILF were generally well tolerated and there was no relevant difference in the occurrence of overall grade 3/4 toxic effects between the two arms . Four patients died during treatment : one in the ILF and three in the PILF arm . The objective response rate was 42 % for both arms . There was no significant difference in therapeutic efficacy between ILF and PILF with respect to progression-free survival ( 4.8 versus 6.2 months ; P = 0.523 ) and overall survival ( 10.7 versus 10.5 months ; P = 0.850 ) . CONCLUSION Both ILF and PILF are active as first-line chemotherapy for AGC . The addition of cisplatin , however , has no clear advantage over ILF 30 patients with advanced metastatic gastric adenocarcinoma , having a measurable indicator lesion , were r and omized ( 1:2 ) to receive ( intravenously ) either weekly 5-fluorouracil alone ( 15 mg/kg ) or combination treatment with cyclophosphamide ( 20 mg/kg ) given on day 1 and 5-FU ( 15 mg/kg ) given weekly on weeks 2 - 5 , beginning on day 8 . The combination cycle was repeated at 6-week intervals . Although the toxic effects of therapy were similar in both arms , the addition of cyclophosphamide to the single-agent 5-FU regimen did not increase either the frequency of objective response ( 5-FU 18 % , combination 16 % ) or improve the median survival of patients with advanced measurable gastric carcinoma ( 5-FU 4.4 months , combination 5.2 months ) . Patients with pretreatment weight loss greater than 10 % had significantly ( p less than 0.05 ) shorter median survival ( 2.8 versus 5.6 months ) compared to patients without weight loss BACKGROUND To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as first-line treatment for advanced gastric cancer ( AGC ) . PATIENTS AND METHODS In this r and omised , open-label , phase III study , patients received cisplatin ( 80 mg/m(2 ) i.v . day 1 ) plus oral capecitabine ( 1000 mg/m(2 ) b.i.d . , days 1 - 14 ) ( XP ) or 5-FU ( 800 mg/m(2)/day by continuous infusion , days 1 - 5 ) ( FP ) every 3 weeks . The primary end point was to confirm noninferiority of XP versus FP for progression-free survival ( PFS ) . RESULTS A total of 316 patients were r and omised to XP ( n = 160 ) or FP ( n = 156 ) . In the per- protocol population , median PFS for XP ( n = 139 ) versus FP ( n = 137 ) was 5.6 versus 5.0 months . The primary end point was met with an unadjusted hazard ratio ( HR ) of 0.81 [ 95 % confidence interval ( CI ) 0.63 - 1.04 , P < 0.001 versus noninferiority margin of 1.25 ] . Median overall survival was 10.5 versus 9.3 months for XP versus FP ( unadjusted HR = 0.85 , 95 % CI 0.64 - 1.13 , P = 0.008 versus noninferiority margin of 1.25 ) . The most common treatment-related grade 3/4 adverse events in XP versus FP patients were as follows : neutropenia ( 16 % versus 19 % ) , vomiting ( 7 % versus 8 % ) , and stomatitis ( 2 % versus 6 % ) . CONCLUSIONS XP showed significant noninferiority for PFS versus FP in the first-line treatment of AGC . XP can be considered an effective alternative to FP BACKGROUND We aim ed to establish the superiority ( or noninferiority if superiority was not achieved ) in terms of time to progression ( TTP ) of irinotecan/5-fluorouracil ( IF ) over cisplatin/5-fluorouracil ( CF ) in chemonaive patients with adenocarcinoma of the stomach/esophagogastric junction . PATIENTS AND METHODS Patients received either IF : i.v . irinotecan 80 mg/m(2 ) 30 min , folinic acid 500 mg/m(2 ) 2 h , 5-fluorouracil ( 5-FU ) 2000 mg/m(2 ) 22 h , for 6/7 weeks or CF : cisplatin 100 mg/m(2 ) 1 - 3 h , with 5-FU 1000 mg/m(2)/day 24 h , days 1 - 5 , every 4 weeks . RESULTS In all , 333 patients were r and omized and treated ( IF 170 , CF 163 ) . Patient characteristics were balanced except more IF patients had Karnofsky performance status 100 % . TTP for IF was 5.0 months [ 95 % confidence interval ( CI ) 3.8 - 5.8 ] and 4.2 months ( 95 % CI 3.7 - 5.5 ) for CF ( P = 0.088 ) . Overall survival ( OS ) was 9.0 versus 8.7 months , response rate 31.8 % versus 25.8 % , time to treatment failure ( TTF ) 4.0 versus 3.4 months for IF and CF , respectively . The difference in TTF was statistically significant ( P = 0.018 ) . IF was better in terms of toxic deaths ( 0.6 % versus 3 % ) , discontinuation for toxicity ( 10.0 % versus 21.5 % ) , severe neutropenia , thrombocytopenia and stomatitis , but not diarrhea . CONCLUSION IF did not yield a significant TTP or OS superiority over CF , and the results of noninferiority of IF were borderline . However , IF may provide a viable , platinum-free front-line treatment alternative for metastatic gastric cancer From January , 1985 , through January , 1987 , 165 patients with advanced gastric cancer were r and omized to receive epirubicin ( E ) alone ( 90 mg/m2 day 1 ) , 5-Fluorouracil ( 5-FU ) alone ( 500 mg/m2 days 1–5 ) , or the combination of E ( 90 mg/m2 day 1 ) and 5-FU ( 400 mg/m2 days 1–5 ) . Courses were repeated every four weeks . Patients were stratified by extent ( locally advanced vs. metastatic ) , evaluability ( measurable vs. non-measurable ) and by history of prior radiotherapy ( yes vs. no ) . R and omization to single arm epirubicin was stopped after 26 patients were enrolled . Objective responses occurred in only 1/16 ( 6 % ) of the patients treated with E alone , 1/40 ( 5 % ) with 5-FU alone and 4/33 ( 12 % ) with both 5-FU and E. There were no significant differences in all eligible patients with respect to time to progression or overall survival in the three treatment arms . Toxicity was primarily hematologic and more pronounced in the combination arm . Neither 5-FU alone , epirubicin alone , or the combination have a major impact in the treatment of gastric carcinoma BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea  ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche Leucovorin ( LV ) enhances the activity of 5-fluorouracil ( 5FU ) . Based on these data , we performed a r and omized trial with 5FU , epirub 
    Output:
    
agent
Within a combination chemotherapy regimen , oral capecitabine is preferred over intravenous 5-fluorouracil (5fu)-that is , epirubicin-cisplatin-capecitabine is preferred over the prior st and ard regimen , epirubicin-cisplatin-5fu (ecf).Epirubicin-oxaliplatin-capecitabine ( eox ) is a reasonable alternative to ecf .
***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: UNLABELLED Various chemotherapies have been used to treat inoperable gastric cancer . Most combination therapies include cisplatin ( CDDP ) and fluoropyrimidine ( 5-FUs ) , which are thought of as key drugs . In the present study , we r and omly compared mitomycin ( MMC ) and CDDP plus doxifluridine ( 5'-DFUR ) , which is an oral 5-FU and an intermediate metabolite of capecitabine ( Xeloda ) , with CDDP plus 5'-DFUR in advanced unresectable gastric cancer . Regimen A was CDDP ( 70 mg/m2 , by 2-hour intravenous drip infusion on day 1 ) , MMC ( 7 mg/m2 , injected intravenously on day 2 ) , and oral 5'-DFUR ( 1200 mg/m2 , on days 4 to 7 , 11 to 14 , 18 to 21 and 25 to 28 ; 3 days rest and 4 days administration ) . Regimen B was identical to regimen A without MMC . RESULTS The response rate was 25.0 % ( 8/32 patients ) in Regimen A , 17.2 % ( 5/29 ) in Regimen B ( p=0.541 ) . The median survival time was 241 days in Regimen A and 179 days in Regimen B ( p=0.498 ) . In Regimen A , although no significant difference was observed , end points such as response rate and suvival improved . Thus , we concluded that a r and omized controlled phase III study with more subjects should be conducted BACKGROUND Irinotecan , in combination with 5-fluorouracil ( 5-FU ) or cisplatin , has demonstrated efficacy against advanced gastric cancer ( AGC ) . PATIENTS AND METHODS Chemotherapy-naive AGC patients were r and omly assigned to receive irinotecan 150 mg/m(2 ) on day 1 , leucovorin 20 mg/m(2 ) and a 22-h infusion of 5-FU 1000 mg/m(2 ) on days 1 and 2 ( ILF ) or ILF plus cisplatin 30 mg/m(2 ) on day 2 ( PILF ) . Treatment was repeated every 2 weeks . RESULTS Of 91 registered patients , 45 patients were treated with ILF and 45 with PILF .  For both arms , 687 chemotherapy cycles were delivered ( median = 7 for ILF and 8 for PILF ) . Both ILF and PILF were generally well tolerated and there was no relevant difference in the occurrence of overall grade 3/4 toxic effects between the two arms . Four patients died during treatment : one in the ILF and three in the PILF arm . The objective response rate was 42 % for both arms . There was no significant difference in therapeutic efficacy between ILF and PILF with respect to progression-free survival ( 4.8 versus 6.2 months ; P = 0.523 ) and overall survival ( 10.7 versus 10.5 months ; P = 0.850 ) . CONCLUSION Both ILF and PILF are active as first-line chemotherapy for AGC . The addition of cisplatin , however , has no clear advantage over ILF 30 patients with advanced metastatic gastric adenocarcinoma , having a measurable indicator lesion , were r and omized ( 1:2 ) to receive ( intravenously ) either weekly 5-fluorouracil alone ( 15 mg/kg ) or combination treatment with cyclophosphamide ( 20 mg/kg ) given on day 1 and 5-FU ( 15 mg/kg ) given weekly on weeks 2 - 5 , beginning on day 8 . The combination cycle was repeated at 6-week intervals . Although the toxic effects of therapy were similar in both arms , the addition of cyclophosphamide to the single-agent 5-FU regimen did not increase either the frequency of objective response ( 5-FU 18 % , combination 16 % ) or improve the median survival of patients with advanced measurable gastric carcinoma ( 5-FU 4.4 months , combination 5.2 months ) . Patients with pretreatment weight loss greater than 10 % had significantly ( p less than 0.05 ) shorter median survival ( 2.8 versus 5.6 months ) compared to patients without weight loss BACKGROUND To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as first-line treatment for advanced gastric cancer ( AGC ) . PATIENTS AND METHODS In this r and omised , open-label , phase III study , patients received cisplatin ( 80 mg/m(2 ) i.v . day 1 ) plus oral capecitabine ( 1000 mg/m(2 ) b.i.d . , days 1 - 14 ) ( XP ) or 5-FU ( 800 mg/m(2)/day by continuous infusion , days 1 - 5 ) ( FP ) every 3 weeks . The primary end point was to confirm noninferiority of XP versus FP for progression-free survival ( PFS ) . RESULTS A total of 316 patients were r and omised to XP ( n = 160 ) or FP ( n = 156 ) . In the per- protocol population , median PFS for XP ( n = 139 ) versus FP ( n = 137 ) was 5.6 versus 5.0 months . The primary end point was met with an unadjusted hazard ratio ( HR ) of 0.81 [ 95 % confidence interval ( CI ) 0.63 - 1.04 , P < 0.001 versus noninferiority margin of 1.25 ] . Median overall survival was 10.5 versus 9.3 months for XP versus FP ( unadjusted HR = 0.85 , 95 % CI 0.64 - 1.13 , P = 0.008 versus noninferiority margin of 1.25 ) . The most common treatment-related grade 3/4 adverse events in XP versus FP patients were as follows : neutropenia ( 16 % versus 19 % ) , vomiting ( 7 % versus 8 % ) , and stomatitis ( 2 % versus 6 % ) . CONCLUSIONS XP showed significant noninferiority for PFS versus FP in the first-line treatment of AGC . XP can be considered an effective alternative to FP BACKGROUND We aim ed to establish the superiority ( or noninferiority if superiority was not achieved ) in terms of time to progression ( TTP ) of irinotecan/5-fluorouracil ( IF ) over cisplatin/5-fluorouracil ( CF ) in chemonaive patients with adenocarcinoma of the stomach/esophagogastric junction . PATIENTS AND METHODS Patients received either IF : i.v . irinotecan 80 mg/m(2 ) 30 min , folinic acid 500 mg/m(2 ) 2 h , 5-fluorouracil ( 5-FU ) 2000 mg/m(2 ) 22 h , for 6/7 weeks or CF : cisplatin 100 mg/m(2 ) 1 - 3 h , with 5-FU 1000 mg/m(2)/day 24 h , days 1 - 5 , every 4 weeks . RESULTS In all , 333 patients were r and omized and treated ( IF 170 , CF 163 ) . Patient characteristics were balanced except more IF patients had Karnofsky performance status 100 % . TTP for IF was 5.0 months [ 95 % confidence interval ( CI ) 3.8 - 5.8 ] and 4.2 months ( 95 % CI 3.7 - 5.5 ) for CF ( P = 0.088 ) . Overall survival ( OS ) was 9.0 versus 8.7 months , response rate 31.8 % versus 25.8 % , time to treatment failure ( TTF ) 4.0 versus 3.4 months for IF and CF , respectively . The difference in TTF was statistically significant ( P = 0.018 ) . IF was better in terms of toxic deaths ( 0.6 % versus 3 % ) , discontinuation for toxicity ( 10.0 % versus 21.5 % ) , severe neutropenia , thrombocytopenia and stomatitis , but not diarrhea . CONCLUSION IF did not yield a significant TTP or OS superiority over CF , and the results of noninferiority of IF were borderline . However , IF may provide a viable , platinum-free front-line treatment alternative for metastatic gastric cancer From January , 1985 , through January , 1987 , 165 patients with advanced gastric cancer were r and omized to receive epirubicin ( E ) alone ( 90 mg/m2 day 1 ) , 5-Fluorouracil ( 5-FU ) alone ( 500 mg/m2 days 1–5 ) , or the combination of E ( 90 mg/m2 day 1 ) and 5-FU ( 400 mg/m2 days 1–5 ) . Courses were repeated every four weeks . Patients were stratified by extent ( locally advanced vs. metastatic ) , evaluability ( measurable vs. non-measurable ) and by history of prior radiotherapy ( yes vs. no ) . R and omization to single arm epirubicin was stopped after 26 patients were enrolled . Objective responses occurred in only 1/16 ( 6 % ) of the patients treated with E alone , 1/40 ( 5 % ) with 5-FU alone and 4/33 ( 12 % ) with both 5-FU and E. There were no significant differences in all eligible patients with respect to time to progression or overall survival in the three treatment arms . Toxicity was primarily hematologic and more pronounced in the combination arm . Neither 5-FU alone , epirubicin alone , or the combination have a major impact in the treatment of gastric carcinoma BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea  ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche Leucovorin ( LV ) enhances the activity of 5-fluorouracil ( 5FU ) . Based on these data , we performed a r and omized trial with 5FU , epirub 
    Output:
    