***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 Using a 2 x 2 factorial design , we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin ( A ) , paclitaxel ( T ) , and cyclophosphamide ( C ) with concurrent doxorubicin and cyclophosphamide ( AC ) followed by paclitaxel ( T ) for disease-free ( DFS ) and overall survival ( OS ) ; to determine whether the dose density of the agents improves DFS and OS ; and to compare toxicities . PATIENTS AND METHODS A total of 2,005 female patients were r and omly assigned to receive one of the following regimens : ( I ) sequential A x 4 ( doses ) -- > T x 4 -- > C x 4 with doses every 3 weeks , ( II ) sequential A x 4 -- > T x 4 -- > C x 4 every 2 weeks with filgrastim , ( III ) concurrent AC x 4 -- > T x 4 every 3 weeks , or ( IV ) concurrent AC x 4 -- > T x 4 every 2 weeks with filgrastim . RESULTS A protocol -specified analysis was performed at a median follow-up of 36 months : 315 patients had experienced relapse or died , compared with 515 expected treatment failures . Dose-dense treatment improved the primary end point , DFS ( risk ratio [ RR ] = 0.74 ; P = .010 ) , and OS ( RR = 0.69 ; P = .013 ) . Four-year DFS was 82 % for the dose-dense regimens and 75 % for the others . There was no difference in either DFS or OS between the concurrent and sequential schedules . There was no interaction between density and sequence . Severe neutropenia was less frequent in patients who received the dose-dense regimens . CONCLUSION Dose density improves clinical outcomes significantly , despite the lower than expected number of events at this time . Sequential chemotherapy is as effective as concurrent chemotherapy BACKGROUND We evaluated capecitabine ( an oral fluoropyrimidine ) and oxaliplatin ( a platinum compound ) as alternatives to infused fluorouracil and cisplatin , respectively , for untreated advanced esophagogastric cancer . METHODS In a two-by-two design , we r and omly assigned 1002 patients to receive triplet therapy with epirubicin and cisplatin plus either fluorouracil ( ECF ) or capecitabine ( ECX ) or triplet therapy with epirubicin and oxaliplatin plus either fluorouracil ( EOF ) or capecitabine ( EOX ) . The primary end point was noninferiority in overall survival for the triplet therapies containing capecitabine as compared with fluorouracil and for those containing oxaliplatin as compared with cisplatin . RESULTS For the capecitabine-fluorouracil comparison , the hazard ratio for death in the capecitabine group was 0.86 ( 95 % confidence interval [ CI ] , 0.80 to 0.99 ) ; for the oxaliplatin-cisplatin comparison , the hazard ratio for the oxaliplatin group was 0.92 ( 95 % CI , 0.80 to 1.10 ) . The upper limit of the confidence intervals for both hazard ratios excluded the predefined noninferiority margin of 1.23 . Median survival times in the ECF , ECX , EOF , and EOX groups were 9.9 months , 9.9 months , 9.3 months , and 11.2 months , respectively ; survival rates at 1 year were 37.7 % , 40.8 % , 40.4 % , and 46.8 % , respectively . In the secondary analysis , overall survival was longer with EOX than with ECF , with a hazard ratio for death of 0.80 in the EOX group ( 95 % CI , 0.66 to 0.97 ; P=0.02 ) . Progression-free survival and response rates did not differ significantly among the regimens . Toxic effects of capecitabine and fluorouracil were similar . As compared with cisplatin , oxaliplatin was associated with lower incidences of grade 3 or 4 neutropenia , alopecia , renal toxicity , and thromboembolism but with slightly higher incidences of grade 3 or 4 diarrhea and neuropathy . CONCLUSIONS Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin , respectively , in patients with previously untreated esophagogastric cancer . ( Current Controlled Trials number , IS RCT N51678883 [ controlled-trials.com ] . ) BACKGROUND Lapatinib , a tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 ( HER2 , also referred to as HER2/neu ) and epidermal growth factor receptor ( EGFR ) , is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy . In this trial , we compared lapatinib plus capecitabine with capecitabine alone in such patients . METHODS Women with HER2-positive , locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab  were r and omly assigned to receive either combination therapy ( lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle ) or monotherapy ( capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle ) . The primary end point was time to progression , based on an evaluation by independent review ers under blinded conditions . RESULTS The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group . The hazard ratio for the independently assessed time to progression was 0.49 ( 95 % confidence interval , 0.34 to 0.71 ; P<0.001 ) , with 49 events in the combination-therapy group and 72 events in the monotherapy group . The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group . This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events . CONCLUSIONS Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab . ( Clinical Trials.gov number , NCT00078572 [ Clinical Trials.gov ] . ) 
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This review demonstrated a favorable gastrointestinal toxicity profile with capecitabine in this novel schedule when given as single agent or in combination therapy with either bevacizumab or lapatinib .
We conclude that capecitabine administered on a 7 days on , 7 days off schedule has limited gastrointestinal toxicity .
Our methodology was based on an analysis of individual patient toxicity data from one phase I single-agent capecitabine and two phase II capecitabine combination studies ( with bevacizumab and lapatinib , respectively ) , focusing specifically on gastrointestinal toxicity