***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: This study was design ed to determine the safety and efficacy of the combination therapy of gemcitabine plus carboplatin when used as a second-line treatment in patients with metastatic breast cancer ( MBC ) . From February 2002 to May 2003 , 30 previously treated patients with adenocarcinoma of the breast received gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin to an area under the curve ( AUC ) of 5 on day 1 . The carboplatin dose was changed to an AUC of 4.5 because of toxicity , with cycles repeated every 3 weeks . Among 30 patients enrolled , 25 were assessable for response rate ( RR ) . There was no complete response ; 9 patients ( 30 % ) had partial response , for an overall RR of 30 % . The median time to progression for the study group was 20.47 weeks ( range , 8 - 46 weeks ) . Treatment-related toxicities included grade 3/4 neutropenia in 50 % of patients ( 20 % of whom had febrile neutropenia ) , grade 3/4 anemia in 26.6 % of patients , and grade 3/4 thrombocytopenia in 30 % . Eleven patients ( 36.67 % ) had grade 1 alopecia , and 1 patient ( 3.33 % ) had grade 2 alopecia . Moderate nausea was observed in 8 patients ( 26.67 % ) , and vomiting occurred in 7 patients . Four patients had asthenia and 3 ( 10 % ) experienced stomatitis . Three patients discontinued treatment because of hematologic toxicity ( thrombocytopenia ) and 2 patients are still receiving treatment . Carboplatin plus gemcitabine is an active combination for patients with MBC despite significant but manageable hematologic toxicity PURPOSE This study was design ed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a st and ard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival . PATIENTS AND METHODS After surgical treatment , 3,121 women with operable breast cancer and involved lymph nodes were r and omly assigned to receive a combination of cyclophosphamide ( C ) , 600 mg/m(2 ) , with one of three doses of doxorubicin ( A ) , 60 , 75 , or 90 mg/m(2 ) , for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2 ) . Tamoxifen was given to 94 % of patients with hormone receptor-positive tumors . RESULTS There was no evidence of a  doxorubicin dose effect . At 5 years , disease-free survival was 69 % , 66 % , and 67 % for patients r and omly assigned to 60 , 75 , and 90 mg/m(2 ) , respectively . The hazard reductions from adding paclitaxel to CA were 17 % for recurrence ( adjusted Wald chi(2 ) P = .0023 ; unadjusted Wilcoxon P = .0011 ) and 18 % for death ( adjusted P = .0064 ; unadjusted P = .0098 ) . At 5 years , the disease-free survival ( + /- SE ) was 65 % ( + /- 1 ) and 70 % ( + /- 1 ) , and overall survival was 77 % ( + /- 1 ) and 80 % ( + /- 1 ) after CA alone or CA plus paclitaxel , respectively . The effects of adding paclitaxel were not significantly different in subsets defined by the protocol , but in an unplanned subset analysis , the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 ( 95 % confidence interval , 0.59 to 0.86 ) for those with estrogen receptor-negative tumors and only 0.91 ( 95 % confidence interval , 0.78 to 1.07 ) for patients with estrogen receptor-positive tumors , almost all of whom received adjuvant tamoxifen . The additional toxicity from adding four cycles of paclitaxel was generally modest . CONCLUSION The addition of four cycles of paclitaxel after the completion of a st and ard course of CA improves the disease-free and overall survival of patients with early breast cancer Abstract A phase II study was conducted to evaluate the activity and toxicity profile of the combination of docetaxel and gemcitabine in anthracycline-resistant advanced breast cancer ( ABC ) . Thirty-nine eligible patients with a median performance status of I ( range , 0–2 ) were enrolled in the study . Treatment consisted of docetaxel 75 mg/m2 in a 1-hr infusion on day 1 preceded by gemcitabine 1000 mg/m2 over 30 min on days 1 and 8 . One hundred eighty-one treatment cycles were administered , 113 ( 62.4 % ) of them at full dose . Relative dose intensity of gemcitabine and of docetaxel was 0.73 and 0.85 , respectively . More common grade 3–4 toxicities included neutropenia ( 49 % ) , anemia ( 10 % ) , fatigue ( 10 % ) , nausea/vomiting ( 8 % ) , and alopecia ( 77 % ) . Seven patients were hospitalized for febrile neutropenia .  Granulocyte colony-stimulating factor ( G-CSF ) administration was required in 90 % of patients . Overall , 14 patients ( 36 % ) responded , 3 ( 7.5 % ) of them completely . Median duration of response was 10.3 months ( range , 4.6–17.5 + ) . Median time to progression was 7 months ( range , 0.2–17.5 + ) and median survival 12.7 months ( range , 2-–20.5 + ) . In conclusion , the combination of docetaxel and gemcitabine , as used in the present study , has moderate activity in anthracycline-resistant ABC . Future studies should incorporate prophylactic administration of G-CSF to reduce the incidence of febrile neutropenia and maintain dose intensity BACKGROUND We wanted to assess the toxicity and efficacy of paclitaxel plus gemcitabine in advanced breast cancer and to confirm whether circulating HER2 extracellular domain ( ECD ) correlates with treatment response . PATIENTS AND METHODS Forty-three patients received paclitaxel 150 mg/m2 followed by gemcitabine 2500 mg/m2 , both on day 1 of 14-day cycles , with a maximum of eight cycles . Serum levels of HER2 ECD were assessed by ELISA . RESULTS All patients were evaluable for toxicity and 42 for efficacy . Overall toxicity was low . Grade 3 neutropenia occurred in 12 % of patients and grade 4 in 17 % , and other grade 3 toxicities in < 5 % . One patient had an allergic infusion reaction . Overall response rate was 71 % [ 95 % confidence interval ( CI ) 62 % to 81 % ] , with 11 patients achieving a complete response ( 26 % ) . With a median follow-up of 26 months , the median time to progression was 16.6 months . Response rate correlated significantly with HER2 ECD , with 42 % of HER2 ECD-positive patients responding versus 83 % of HER2 ECD-negative patients ( P = 0.02 ) . Furthermore , response duration was shorter in patients with positive HER2 ECD levels ( 7.9 versus 14.4 months ; P = 0.04 ) . CONCLUSIONS Paclitaxel plus gemcitabine given as an every 2-weeks schedule is a well tolerated and active regimen in advanced breast carcinoma . This is an attractive combination to use when anthracyclines are not indicated , such as in HER2 positive cases that receive trastuzumab . In addition , elevated levels of HER2 ECD adversely affect the efficacy of treatment 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 PURPOSE A multicenter Phase II trial was performed to investigate the efficacy and tolerance of combined docetaxel and gemcitabine + /- recombinant human granulocyte colony-stimulating factor ( G-CSF ) in patients with metastatic breast cancer . PATIENTS AND METHODS Fifty-two patients participated in this trial , 51 of whom are evaluable for response . Thirty-eight patients received this combination as first-line chemotherapy , and 14 patients received this combination as second-line chemotherapy , including 10 patients who had failed anthracyclines .  Therapy consisted of 1500 mg/m2 gemcitabine and 50 mg/m2 docetaxel , both administered on days 1 and 15 every 4 weeks . Depending on the absolute neutrophil counts on the day of scheduled chemotherapeutic drug administration , a 5-day course of 5 microg/kg G-CSF was given . RESULTS The overall response rate was 60.5 % ( 95 % confidence interval , 43.4 - 75.9 % ) in patients receiving docetaxel plus gemcitabine as first-line chemotherapy , including 4 complete responses ( 10.5 % ) and 19 partial remissions ( 50 % ) ; 9 patients ( 24 % ) had disease stabilization , and only 5 ( 13 % ) progressed . Second-line treatment with this regimen result ed in 6 of 14 ( 43 % ) objective responses , 5 had stable disease , and 3 progressive disease . The median time to progression was 8.5 months in the first-line setting and 6.6 months in the second-line setting , respectively . After a median follow-up time of 15 months , 36 patients ( 69 % ) are still alive with metastatic disease . Myelosuppression was commonly observed ; WHO grade 3 or 4 neutropenia , however , occurred in only 15 ( 29 % ) patients and was complicated by septicemia in 2 cases ; grade 3 anemia was seen in 1 patient ( 2 % ) . Severe ( grade 3 ) nonhematological toxicity except for alopecia was rarely observed and included nausea/vomiting in 3 ( 6 % ) , stomatitis in 2 ( 4 % ) , anaphylaxis in 2 , and peripheral neuropathy , skin toxicity , and increase of liver enzymes each in one patient . CONCLUSION Our data suggest that docetaxel and gemcitabine with and without G-CSF is an effective and fairly well-tolerated regimen for the treatment of advanced breast cancer . It might be particularly useful in patients exposed previously to adjuvant or palliative anthracyclines and /or alkylating agents Purpose : Advanced breast cancer ( ABC ) is an incurable disease . St and ard first-line treatment for patients with HER-2/neu overexpressing tumors includes the combination of the humanized monoclonal antibody trastuzumab with chemotherapy , mainly paclitaxel . This combination is the first to demonstrate a survival advantage in this group of patients . To improve on these results , we investigated a triplet , paclitaxel-gemcitabine-trastuzumab ( TGH ) , in a phase II study . Patients and Methods : Patients with ABC were accrued to the study . Treatment consisted of paclitaxel 80 mg/m2/week , gemcitabine 1000 mg/m2 every 2 weeks , and trastuzumab 4 mg/kg loading dose and then 2 mg/kg/week . Patients were treated on study for a total of 12 weeks . Response evaluation was performed at the end of the 12 weeks . Continuation of treatment beyond the 12 
    Output:
    
Conclusion Available data do not support the acceptance of gemcitabine as a st and ard therapeutic option in women with metastatic breast cancer in the third-line or greater setting , nor should it be considered as first-line therapy in anthracycline naïve women .
Gemcitabine appears to be most effective when administered with a taxane ( docetaxel/paclitaxel ) in the first- or second-line setting , with gemcitabine/taxane combinations representing a viable alternative to currently accepted taxane combinations such as capecitabine/docetaxel .
There is no evidence at this time to support the use of gemcitabine triplets , given the equal efficacy to anthracycline triplets and the added toxicity