***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: Objectives The aim of this phase II study was to evaluate the response rate to gemcitabine combined with cisplatin in patients with locally advanced , metastatic or recurrent biliary tract cancer who had received no prior chemotherapy . Methods The treatment consisted of cisplatin 70 mg/m2 in intravenous infusion followed by gemcitabine 1,250 mg/m2 in 30-min intravenous infusion on days 1 and 8 , repeated every 3 weeks until disease progression , unacceptable toxicity , patient ’s refusal or up to 8 cycles . Results Thirty-nine patients with advanced biliary cancer were enrolled between March 2003 and August 2003 . Fourteen patients ( 40 % ) had gall bladder cancer and 20 patients ( 57 % ) had cholangiocarcinoma . Thirty-two patients ( 91 % ) had metastatic disease at study entry with liver being the most commonly involved site of metastasis . About 84.5 and 94.2 % of the initially planned dose were administered for gemcitabine and cisplatin , respectively . In the ITT population ( n = 35 ) , six partial responses were observed for an objective response rate of 17.1 % ( 95 % CI ; 4.7–29.6 % ) . Ten patients ( 28.6 % ) had stable disease , 16 ( 45.7 % ) progressed , and three ( 8.6 % ) were not evaluable . For the 35 patients in the ITT population , the median overall survival time was 8.6 months ( 95 % CI ; 6.1–10.4 months ) . The median time to disease progression was 3.2 months ( 95 % CI ; 2.3–4.9 months ) and the median time to treatment failure was 3.1 months ( 95 % CI ; 1.9–4.1 months ) . Among the six tumor responders , the median duration of tumor response was 7.3 months ( 95 % CI ; 5.6–11.0 months ) . The most common grade 3/4 maximum toxicities were nausea ( 3.4 % ) and vomiting ( 2.7 % ) . Conclusion The combination chemotherapy with gemcitabine and cisplatin in this trial demonstrated moderate antitumor activity with favorable toxicity profile Owing to the lack of r and omised controlled trials no st and ard of chemotherapy exists in the treatment of advanced biliary tract carcinoma .  5-fluorouracil or gemcitabine is recommended based on small and predominately phase II trials . The aim of this analysis was to analyse existing trials , even small and nonr and omised , and identify superior regimens . Chemotherapy  trials published in English from 1985 to July 2006 were analysed as well as ASCO abstract s from 1999 to 2006 .  Response rate ( RR = CR+PR ) , tumour control rate ( TCR = CR+PR+SD ) , time to tumour progression ( TTP ) , overall survival ( OS ) , and toxicity were analysed . One hundred and four trials comprising 112 trial arms and 2810 patients , thereof 634 responders and 1368 patients with tumour control were analysed .  Pooled RR and TCR were 22.6 and 57.3 % , respectively . Significant correlations of RR and TCR with survival times were found . Subgroup analysis showed superior RRs for gallbladder carcinoma ( GBC ) compared with cholangiocarcinoma , but shorter OS for GBC . Furthermore , superior RRs and TCRs of gemcitabine and platinum containing regimens were found with highest RRs and TCRs in the combination subgroup . Based on published results of predominately phase II trials , gemcitabine combined with platinum compounds represents the provisional st and ard of chemotherapy in advanced biliary tract cancer , unless a new evidence -based st and ard has been defined BACKGROUND Combination chemotherapy with gemcitabine and a platinum-based agent is regarded as a st and ard treatment for patients with advanced biliary-tract cancer . Results of phase 2 trials of single-agent erlotinib in biliary-tract cancer and of gemcitabine plus erlotinib in pancreatic cancer have shown modest benefits . Therefore , we aim ed to investigate the efficacy of gemcitabine and oxaliplatin plus erlotinib versus chemotherapy alone for advanced biliary-tract cancer . METHODS In this open label , r and omised , phase 3 trial , we r and omly assigned patients ( in a 1:1 ratio ) with metastatic biliary-tract cancer ( cholangiocarcinoma , gallbladder cancer , or ampulla of Vater cancer ) to receive either first-line treatment with  chemotherapy alone ( gemcitabine 1000 mg/m(2 ) on day 1 and oxaliplatin 100 mg/m(2 ) on day 2 ) or chemotherapy plus erlotinib ( 100 mg daily ) . Treatment was repeated every 2 weeks until disease progression or unacceptable toxic effects . R and omisation was done central ly ( stratified by participating centre and presence of measurable lesion ) . The primary endpoint was progression-free survival . Analyses were by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT01149122 . FINDINGS 133 patients were r and omly assigned to the chemotherapy alone group and 135 to the chemotherapy plus erlotinib group . The groups were balanced except for a higher proportion of patients with cholangiocarcinoma in the group given erlotinib than in the chemotherapy alone group ( 96 [ 71 % ] patients vs 84 [ 63 % ] ) . Median progression-free survival was 4·2 months ( 95 % CI 2·7 - 5·7 ) in the chemotherapy alone group and 5·8 months ( 95 % CI 4·6 - 7·0 ) in the chemotherapy plus erlotinib group ( hazard ratio [ HR ] 0·80 , 95 % CI 0·61 - 1·03 ; p=0·087 ) . Significantly more patients had an objective response  in the chemotherapy plus erlotinib group than in the chemotherapy alone group ( 40 patients vs 21 patients ; p=0·005 ) , but median overall survival was the same in both groups ( 9·5 months [ 95 % CI 7·5 - 11·5 ] in the chemotherapy alone group and 9·5 months [ 7·6 - 11·4 ] in the chemotherapy plus erlotinib group ; HR 0·93 , 0·69 - 1·25 ; p=0·611 ) . All-cause deaths within 30 days of r and om assignment occurred in one ( 1 % ) of the patients in the chemotherapy alone group and in four ( 3 % ) of those in the chemotherapy plus erlotinib group . The most common grade 3 - 4 adverse event was febrile neutropenia ( eight [ 6 % ] patients in the chemotherapy alone group and six [ 4 % ] in the chemotherapy plus erlotinib group ) . No patient died of treatment-related causes during the study . Subgroup analyses by primary site of disease showed that for patients with cholangiocarcinoma , the addition of erlotinib to chemotherapy significantly prolonged median progression-free survival ( 5·9 months [ 95 % CI 4·7 - 7·1 ] for chemotherapy plus erlotinib vs 3·0 months [ 1·1 - 4·9 ] for chemotherapy alone ; HR 0·73 , 95 % CI 0·53 - 1·00 ; p=0·049 ) . INTERPRETATION Although no significant difference in progression-free survival was noted between groups , the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity and might be a treatment option for patients with cholangiocarcinoma . FUNDING None The primary objective of this study was to determine the response rates of the gemcitabine and cisplatin combination in unresectable gall bladder cancer patients . The secondary objectives were to evaluate the toxicity , time to progressive disease , and overall survival . Chemonaïve patients with histologically proven , unresectable bidimensionally measurable gall bladder cancer were enrolled into this study . All patients were required to have a Zubrod 's performance status ⩽2 , no prior radiotherapy , and adequate major organ function . Patients received gemcitabine ( 1000 mg m−2 intravenously over 30–60 min ) on days 1 and 8 , and cisplatin ( 70 mg m−2 intravenously over 2 h ) on day 1 , every 21 days . Response assessment was done by a CT scan after every other cycle of chemotherapy . In all , 30 patients were eligible for efficacy and toxicity analysis . There were four ( 13.3 % ) complete responders , seven ( 23.3 % ) partial responders , and seven ( 23.3 % ) with stable disease , with four ( 13.2 % ) patients showing disease progression . The median time to progression was 18 weeks ( 95 % confidence interval ( CI ) 14–24 weeks ) , and the median duration of response was 13.5 weeks ( range 5.5–104 weeks ) . The median overall survival was 20 weeks ( 95 % CI 14–31 weeks ) , with 1-year survival rate of 18.6 % . WHO grade 3 or 4 anaemia was seen in seven ( 23.3 % ) and four ( 13.3 % ) patients , respectively . Five ( 16.6 % ) patients each experienced grade 3 or 4 neutropenia , and grade 3 or 4 thrombocytopenia was seen in three ( 10 % ) and two ( 6.6 % ) patients , respectively . The present study shows that gemcitabine/cisplatin combination is well tolerated and active in advanced unresectable gall bladder cancer Background : A British r and omised study of gemcitabine plus cisplatin ( GC ) combination showed promising results in biliary tract cancer ( BTC ) patients . In our study , we evaluated the efficacy and safety of this combination compared with gemcitabine alone ( G ) in Japanese BTC patients . Methods : Overall , 84 advanced BTC patients were r and omised to either cisplatin 25 mg m−2 plus gemcitabine 1000 mg m−2 on days 1 , 8 of a 21-day cycle ( GC-arm ) , or single-agent gemcitabine 1000 mg m−2 on days 1 , 8 and 15 of a 28-day cycle ( G-arm ) . Treatments were repeated for at least 12 weeks until disease progression or unacceptable toxicity occurred , up to a maximum of 48 weeks . Results : A total of 83 patients were included in the analysis . For the GC and G-arms , respectively , the 1-year survival rate was 39.0 vs 31.0 % , median survival time 11.2 vs 7.7 months , median progression-free survival time 5.8 vs 3.7 months and overall response rate 19.5 vs 11.9 % . The most common grade 3 or 4 toxicities ( GC-arm/G-arm ) were neutropenia ( 56.1%/38.1 % ) , thrombocytopenia ( 39.0%/7.1 % ) , leukopenia ( 29.3%/19.0 % ) , haemoglobin decrease ( 36.6%/16.7 % ) and γ-GTP increase ( 29.3%/35.7 % ) . Conclusions : Gemcitabine plus cisplatin combination therapy was found to be effective and well tolerated , suggesting that it could also be a st and ard regimen for Japanese patients BACKGROUND There is no established st and ard chemotherapy for patients with locally advanced or metastatic biliary tract cancer . We initially conducted a r and omized , phase 2 study involving 86 patients to compare cisplatin plus gemcitabine with gemcitabine alone . After we found an improvement in progression-free survival , the trial was extended to the phase 3 trial reported here . METHODS We r and omly assigned 410 patients with locally advanced or metastatic cholangiocarcinoma , gallbladder cancer , or ampullary cancer to receive either cisplatin ( 25 mg per square meter of body-surface area ) followed by gemcitabine ( 1000 mg per square meter on days 1 and 8 , every 3 weeks for eight cycles ) or gemcitabine alone ( 1000 mg per square meter on days 1 , 8 , and 15 , every 4 weeks for six cycles ) for up to 24 weeks . The primary end point was overall survival . RESULTS After a median follow-up of 8.2 months and 327 deaths , the median overall survival was 11.7 months among the 204 patients in the cisplatin-gemcitabine group and 8.1 months among the 206 patients in the gemcitabine group ( hazard ratio , 0.64 ; 95 % confidence interval , 0.52 to 0.80 ; P<0.001 ) . The median progression-free survival was 8.0 months in the cisplatin-gemcitabine group and 5.0 months in the gemcitabine-only group ( P<0.001 ) . In addition , the rate of tumor control among patients in the cisplatin-gemcitabine group was significantly increased ( 81.4 % vs. 71.8 % , P=0 
    Output:
    
Toxicities were generally acceptable and manageable .
Heterogeneity in study design s and data collected prevented formal meta- analysis , however exploratory assessment s suggested that efficacy did not vary with primary tumor site ( gallbladder vs. others ) , disease stage ( metastatic vs. locally advanced ) , or geographic origin ( Asia vs. other ) .
Incidence of grade 3/4 toxicities was not related to gemcitabine dose or cisplatin frequency .
Despite individual variation in study design s , the evidence presented suggests that gemcitabine-cisplatin is effective in patients from a diverse range of countries and with heterogeneous disease characteristics .
No substantial differences in toxicity were observed among the different dosing schedules of gemcitabine and cisplatin