You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741.
Abstract 1:
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


Title 2:
Capecitabine and oxaliplatin for advanced esophagogastric cancer.
Abstract 2:
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 ] . )


Title 3:
Lapatinib plus capecitabine for HER2-positive advanced breast cancer.
Abstract 3:
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 ] . )
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