***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: We present experience from a phase II r and omized clinical trial , comparing st and ard gemcitabine as monotherapy with low-dose gemcitabine in long infusion in a doublet with cisplatin at reduced dose for patients with non-small cell lung cancer ( NSCLC ) and who are unfit for st and ard platin-based chemotherapy . Eligible patients had microscopically confirmed NSCLC in stage IIIB ( wet ) or IV , were chemo-naive , and were in poor performance status or presented with significant comorbidity .  St and ard treatment with gemcitabine , 1250 mg/m2 in 20–30 min on days 1 and 8 as monotherapy ( arm A ) was compared with low-dose gemcitabine in long infusion ( 200 mg/m2 in 6 h on day 1 ) and cisplatin at 60 mg/m2 on day 2 ( arm B ) . Both treatment schedules were repeated every 3 weeks until disease progression , unacceptable toxicity , or to a maximum of six cycles . A total of 112 patients ( 83 male , 29 female , median age 66 years ) were r and omized between arm A ( 57 patients ) and B ( 55 patients ) . The two groups were balanced for prognostic factors . Fifty-three patients in arm A and 52 in arm B received at least one application of chemotherapy and were evaluable for toxicity and response . The median number of cycles was four and five for arms A and B , respectively . Except for grade 3 anemia ( one patient in arm A and two in arm B ) , no other major toxicity was seen . Regarding response to treatment , arm B was superior : 1 complete response and 13 partial remissions ( response rate 26.9 % ) as compared with five partial remissions ( response rate 9.4 % ) in arm A ( P<0.01 ) . The median time to progression was 3.8 and 5.6 months , and the median survival was 4.3 and 6.8 months for arms A and B , respectively ( P<0.05 ) . Treatment with low-dose gemcitabine in long infusion and cisplatin at reduced dose has very low toxicity , is effective , was found to be superior to monotherapy with gemcitabine in st and ard doses , and is suitable for patients with NSCLC who can not tolerate a st and ard platin-based doublet Objective : Gemcitabine in low dose in prolonged infusion is a treatment with documented activity against a variety of tumors . We here report the first r and omized trial to compare st and ard brief and low-dose prolonged infusion of gemcitabine . Patients and Methods : Eligible patients had non-small cell lung cancer in stage IIIB ( wet ) or IV , Karnofsky performance status 100 to 70 ( Eastern Cooperative Oncology Group 0–2 ) , measurable disease , were chemonaïve and fulfilled the st and ard criteria for chemotherapy . In arm A ( st and ard treatment ) , gemcitabine was given at 1250 mg/m2 in 20 to 30 minutes and in arm B ( prolonged infusion ) at 250 mg/m2 in 6 hours infusion . All patients received gemcitabine on days 1 and 8 and cisplatin at 75 mg/m2 on day 2 of a 3-week cycle for four cycles , followed by two cycles of gemcitabine as monotherapy . Results : A total of 249 patients ( 188 men and 61 women , median age 58 years ) were r and omized between arm A ( 125 patients ) and arm B ( 124 patients ) . Adenocarcinoma ( 53.9 % ) was the predominant histologic type ; 92 % of patients were in stage IV . The two groups were balanced for prognostic factors ; however , group A had fewer patients with significant weight loss and no patient with lung cancer as a second malignancy or after radiotherapy for brain metastases . Grade 3 or greater toxicity was rare : anemia in 0.8 and 3.2 % , neutropenia in 21.6 and 22.6 % , thrombocytopenia in 0 and 1.6 % , and nausea/vomiting in 4 and 8.1 % for arms A and B , respectively . Alopecia was seen in 54.5 % of patients in arm B , as compared with 9.7 % in arm A. No patient died of treatment-related toxicity . During cycle 5 , 47.7 % of patients in arm A and 60.7 % in arm B reported improved well-being , as compared with the status before chemotherapy . Patients in arm A had no complete remission , 32.8 % partial responses , 48 % minimal responses or stable disease , 13.6 % progressions , and 5.6 % were not evaluable . For arm B , the corresponding figures are as follows : complete remission 0.8 % , partial responses 46 % ( for overall response rate of 46.8 % ) , minimal responses or stable disease 36.3 % , progression 12.1 % , and not evaluable 4.8 % . Median progression-free survival was 5.5 and 6.0 months , median overall survival was 10.1 and 10.0 months , and 1-year survival was 46.6 and 41.1 % for arms A and B , respectively . For the 71 patients with squamous carcinoma , arm B seems superior to arm A , as seen by the higher overall response rate ( 51.3 versus 35.5 % ) , longer median progression-free survival ( 6.2 versus 4.9 months ) , and longer median survival ( 11.3 versus 8.5 months ) . However , because of the small number of patients , these differences did not reach the level of statistical significance . Conclusion : In the treatment of advanced non-small cell lung cancer , gemcitabine in low dose in prolonged infusion in combination with cisplatin has low toxicity and has activity comparable with gemcitabine in higher dose in st and ard brief infusion . Low-dose gemcitabine may be preferred for incurable cancer among economically deprivileged patients . In addition , apparent superior activity against squamous carcinoma opens new perspectives and deserves further research PURPOSE Gemcitabine in low-dose prolonged infusion is a treatment with documented activity against a variety of tumors . The present study was conducted to evaluate the efficacy and safety of the combination of gemcitabine at a low-dose prolonged infusion in comparison with st and ard dose gemcitabine with carboplatin in chemonaive patients with advanced non-small cell lung cancer ( NSCLC ) . MATERIAL S AND METHODS Sixty chemonaive patients with stage IIIB or IV NSCLC were included . Patients were r and omly assigned 1:1 to receive 350 mg/m 2 gemcitabine in a 6-h infusion on days 1 and 8 and carboplatin area under the serum concentration time curve ( AUC ) 5 on day 1 versus gemcitabine 1,000 mg/m 2 on days 1 and 8 and carboplatin AUC 5 on day 1 ( 3-week cycle both ) . A total of 118 chemotherapy cycles , with a median of 4 cycles per patient ( range 2 - 6 ) , and 134 chemotherapy cycles , with a median of 4.47 cycles per patient ( range 3 - 6 ) were administered in st and ard and low infusional dose arm , respectively . RESULTS Among patients in the st and ard arm , 40 % had overall response rate ( ORR ) , 33.3 % had stable disease and 26.6 % had progressive disease , while in low-dose infusional arm , 36.6 % had ORR , 36.3 % had stable disease and 26.6 % had progressive disease ( P = 0.992 ) . Median progression-free survival was 5.5 months and 5.4 months , median overall survival was 9.7 months and 10.7 months , and 1-year survival was 33.7 % and 36.6 % in st and ard arm and low-dose infusion arm , respectively . Grade 3/4 toxicity was rare . CONCLUSION In NSCLC , gemcitabine low-dose prolonged infusion with carboplatin has low toxicity , especially thrombocytopenia , and has an activity comparable with gemcitabine given in higher dose in st and ard infusion Gemcitabine ( GEM ) is a novel nucleoside analogue with a unique mechanism of action . Preliminary studies have shown a mild , schedule-dependent toxic profile with a broad range of MTDs and promising antitumor activity in various solid tumors . This phase I study describes the infusion length-effect relationships of low(300 mg/m2 ) and high-dose ( 875 mg/m2 ) GEM , administered on days 1 , 8 and 15 at 4-week intervals in a step-wise escalation of duration ( > 33 % ) at a starting level of 60 minutes . At least 3 patients entered each infusion-level step and 3 more cases were treated in the presence of significant toxicity . Conservative criteria for toxicity were employed , including treatment delay until recovery with infusion de-escalation in the subsequent course . Forty seven patients ( 29 at low- and 18 at high-dose GEM levels ) with various solid tumors , including 9 ( taken as a reference ) who had received the same dose-levels over 30 min . entered the study . All but 9 patients ( with pancreatic cancer ) had been previously treated with chemotherapy and all had extensive visceral disease . A striking infusional-effect relationship was observed at both GEM dose levels . Four escalation steps were required to define the maximum tolerated infusion time ( MTIT ) at 6 hours for 300 mg/m2 GEM , with leucopenia being dose-limiting . At 875 mg/m2 , although no limiting toxicity was observed ( in spite of increased severity of leucopenia ) , no escalation was attempted following the 1 hour infusion , due to the limiting rate ( 58 % of 12 patients ) of toxic delay requiring shorter infusions . Toxicity was usually mild ( no grade 4 event was recorded ) showing the usual profile , although there was a trend towards increased non-hematologic toxicity ( i.e. LFT abnormalities ) as compared with the MTD previously defined using 30-min . infusion schedule ( 1,370 mg/m2 ) . Eight patients achieved a PR : 1 with NSCLC , 1 with gastric and 2 with bladder cancer at 300 mg/m2 ( 1 with a 3- and 3 with a 6-hour infusion ) and 2 with pancreatic , 1 with cervical and another with bladder cancer at 875 mg/m2 ( all but one with a 1-hour infusion ) . These data clearly suggest that the infusion duration is an important independent factor that influences the clinical effects of GEM . The present study not only defined the toxic profiles and the MTITs of the selected dose-levels but demonstrated that GEM retained the antitumor activity at doses as small as 300 mg/m2 when given as a prolonged infusion . Further studies should clarify the underlying mechanism(s ) responsible for the erratic dose-effect relationships of GEM and establish the optimal dose-infusion level in the treatment of solid tumors PURPOSE We conducted a phase I trial of the novel nucleoside analog , gemcitabine , in chemotherapy-naive patients with advanced non-small-cell lung cancer ( NSCLC ) to determine the maximum-tolerated dose and efficacy in this population . PATIENT AND METHODS Eligibility requirements included stage III or IV NSCLC , performance status < or = 1 , and no prior chemotherapy .  Gemcitabine was administered as a 30-minute intravenous infusion weekly for 3 weeks every 4 weeks . We enrolled patients at doses that ranged from 1,000 to 2,800 mg/m2/wk ( three patients per cohort ) . Responses were assessed after every two courses ( 8 weeks ) . RESULTS We treated 33 chemotherapy-naive patients with stage III ( n = 5 ) or IV ( n = 28 ) NSCLC . Most had performance status 1 , and 67 % had adenocarcinoma . Eight of 32 assessable patients ( 25 % ) achieved a partial response . The projected median survival duration ( all patients ) is 49 weeks . The maximum-tolerated dose was 2,200 mg/m2/wk for 3 weeks every 4 weeks ; dose-limiting toxicity was myelosuppression and reversible transaminase elevation . Other side effects were consistently mild . The maximum dose-intensity achieved with the first two cycles was 2,362 mg/m2/wk for 3 weeks every 4 weeks , which is a feasible phase II starting dose . CONCLUSION This study estimates a phase II starting dose of gemcitabine in chemotherapy-naive patients to be 2,400 mg/m2/wk for 3 consecutive weeks every 4 weeks ; this is much higher than that previously reported in heavily pretreated patients . Twenty-five percent of patients with advanced NSCLC achieved a partial response to gemcitabine . This significant activity in conjunction with a very favorable toxicity profile supports the further evaluation of gemcitabine in combination with other active agents Summary Background : Gemcitabine is a pro-drug that has to be phosphorylated to gemcitabine-triphosphate in order to exhibit its antineoplastic activity . This reaction involves the enzyme deoxycytidine kinase which is saturated at plasma concentrations following st and ard 30-min infusions . Pharmacological studies indicate that prolonged administration of gemcitabine might result in higher int 
    Output:
    
All studies assessed the efficacy and safety of Gem administered as a prolonged low-dose infusion ( P-LDI ) and reported that Gem administered as P-LDI was effective and well tolerated .
Conclusion Gem administered as P-LDI is effective , safe , and economical , especially suited for patients with poor performance status or without good economic condition