***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: BACKGROUND Several studies have shown the efficacy , tolerability , and ease of administration of pemetrexed-an antifolate antineoplastic agent-in  patients with advanced non-small-cell lung cancer . We assessed pemetrexed as maintenance therapy in patients with this disease . METHODS This r and omised double-blind study was undertaken in 83 centres in 20 countries . 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy  were r and omly assigned ( 2:1 ratio ) to receive pemetrexed ( 500 mg/m(2 ) , day 1 ) plus best supportive care ( n=441 ) or placebo plus best supportive care ( n=222 ) in 21-day cycles until disease progression . Treatment was r and omised with the Simon and Pocock minimisation method . Patients and investigators were masked to treatment . All patients received vitamin B(12 ) , folic acid , and dexamethasone . The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT00102804 . FINDINGS All r and omly assigned participants were analysed . Pemetrexed significantly improved progression-free survival ( 4.3 months [ 95 % CI 4.1 - 4.7 ] vs 2.6 months [ 1.7 - 2.8 ] ; hazard ratio [ HR ] 0.50 , 95 % CI 0.42 - 0.61 , p<0.0001 ) and overall survival ( 13.4 months [ 11.9 - 15.9 ] vs 10.6 months [ 8.7 - 12.0 ] ; HR 0.79 , 0.65 - 0.95 , p=0.012 ) compared with placebo . Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group ( 21 [ 5 % ] vs three [ 1 % ] ) . Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo ( 70 [ 16 % ] vs nine [ 4 % ] ; p<0.0001 ) , specifically fatigue ( 22 [ 5 % ] vs one [ 1 % ] , p=0.001 ) and neutropenia ( 13 [ 3 % ] vs 0 , p=0.006 ) . No  pemetrexed-related deaths occurred . Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy ( 227 [ 51 % ] vs 149 [ 67 % ] ; p=0.0001 ) . INTERPRETATION Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer . FUNDING Eli Lilly BACKGROUND A r and omized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil ( TPF ) with cisplatin and fluorouracil ( PF ) , followed by chemoradiotherapy . METHODS We r and omly assigned 501 patients ( all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were c and i date s for organ preservation ) to receive either TPF or PF induction chemotherapy  , followed  by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week . The primary end point was overall survival . RESULTS With a minimum of 2 years of follow-up ( > or =3 years for 69 % of patients ) , significantly more patients survived in the TPF group than in the PF group ( hazard ratio for death , 0.70 ; P=0.006 ) . Estimates of overall survival at 3 years were 62 % in the TPF group and 48 % in the PF group ; the median overall survival was 71 months and 30 months , respectively ( P=0.006 ) . There was better locoregional control in the TPF group than in the PF group ( P=0.04 ) , but the incidence of distant metastases in the two groups did not differ significantly ( P=0.14 ) . Rates of neutropenia and febrile neutropenia were higher in the TPF group ; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group . CONCLUSIONS Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy . ( Clinical Trials.gov number , NCT00273546 [ Clinical Trials.gov ] . ) BACKGROUND We studied the combination of pemetrexed , a multi-targeted antifolate , and cetuximab , an mAb against the epidermal growth factor receptor , with radiotherapy in poor prognosis head and neck cancer . PATIENTS AND METHODS Patients received pemetrexed on days 1 , 22 , and 43 on a dose-escalation scheme with starting level ( 0 ) 350 mg/m(2 ) ( level -1 , 200 mg/m(2 ) ; level + 1 , 500 mg/m(2 ) ) with concurrent radiotherapy ( 2 Gy/day ) and cetuximab in two separate cohorts , not previously irradiated ( A ) and previously irradiated ( B ) , who received 70 and 60 - 66 Gy , respectively . Genetic polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase were evaluated . RESULTS Thirty-two patients were enrolled . The maximum tolerated dose of pemetrexed was 500 mg/m(2 ) in cohort A and 350 mg/m(2 ) in cohort B. Prophylactic antibiotics were required . In cohort A , two dose-limiting toxicities ( DLTs ) occurred ( febrile neutropenia ) , one each at levels 0 and + 1 . In cohort B , two DLTs occurred at level + 1 ( febrile neutropenia ; death from perforated duodenal ulcer and sepsis ) . Grade 3 mucositis was common . No association of gene polymorphisms with toxicity or efficacy was evident . CONCLUSION The addition of pemetrexed 500 mg/m(2 ) to cetuximab and radiotherapy is recommended for further study in not previously irradiated patients Purpose This phase I study characterized the pharmacokinetics of free and total platinum derived from cisplatin administered alone and in combination with pemetrexed . Secondary objectives were to assess the pharmacokinetics of pemetrexed when it is combined with cisplatin as well as to evaluate the safety profile and document antitumor activity associated with this combination . Methods An open-label , two-arm , cross-over phase 1 study was performed in patients with squamous cell carcinoma of the head and neck , age ≥18 years , an Eastern Cooperative Oncology Group performance status of 0–2 , and adequate organ function . Blood sample s were taken and pharmacokinetics evaluated for the first two cycles using noncompartmental analysis . Patients received either pemetrexed ( 500 mg m−2 ) plus cisplatin ( 75 mg m−2 ) administered in cycle 1 followed by cisplatin alone in cycle 2 ; or in the reverse order ( i.e. , cisplatin alone in cycle 1 followed by pemetrexed plus cisplatin in cycle 2 ) . Each treatment cycle was 21 days and patients received folic acid , vitamin B12 supplementation , and dexamethasone prophylaxis . After the first two cycles , patients continued study treatment with pemetrexed plus cisplatin every 3 weeks up to a maximum of six total treatment cycles . Toxicities were grade d by the investigators according to the National Cancer Institute Common Toxicity Criteria for Adverse Events ( CTCAE ) , version 3.0 . Results A total of 13 patients were treated ; one patient was discontinued from the study after cycle 1 for failure to meet baseline eligibility criteria for renal function . The ratios and 90 % confidence intervals ( CI ) comparing the pharmacokinetics for cisplatin administered with pemetrexed to those for cisplatin administered alone for free platinum were : Cmax = 1.08 ( CI : 0.92 , 1.27 ) and AUC = 0.93 ( CI : 0.82 , 1.06 ) ; and , total platinum were : Cmax = 0.97 ( CI : 0.88 , 1.06 ) and AUC = 0.87 ( CI : 0.81 , 0.93 ) . These results indicate that platinum pharmacokinetics ( free and total ) are similar , whether cisplatin is administered alone or combined with pemetrexed . The pemetrexed pharmacokinetic results were consistent with those from previous single-agent pemetrexed studies and a previous study of pemetrexed in combination with cisplatin . The combination of pemetrexed and cisplatin did not show any unexpected toxicities . Consistent with the platinum pharmacokinetic results , co-administration with pemetrexed did not appear to enhance cisplatin-related toxicities . Of the 13 treated patients , 11 had stable disease as the best overall response and 2 had progressive disease . Conclusions The pharmacokinetics of free platinum derived from cisplatin were not altered by co-administration with pemetrexed , and in agreement with this , no unexpected cisplatin-induced toxicities were observed when these drugs were combined PURPOSE Patients with malignant pleural mesothelioma , a rapidly progressing malignancy with a median survival time of 6 to 9 months , have previously responded poorly to chemotherapy . We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone . PATIENTS AND METHODS Chemotherapy-naive patients who were not eligible for curative surgery were r and omly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 , or cisplatin 75 mg/m2 on day 1 . Both regimens were given intravenously every 21 days . RESULTS A total of 456 patients were assigned : 226 received pemetrexed and cisplatin , 222 received cisplatin alone , and eight never received therapy .  Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm ( P = .020 , two-sided log-rank test ) . The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77 . Median time to progression was significantly longer in the pemetrexed/cisplatin arm : 5.7 months versus 3.9 months ( P = .001 ) . Response rates were 41.3 % in the pemetrexed/cisplatin arm versus 16.7 % in the control arm ( P < .0001 ) . After 117 patients had enrolled , folic acid and vitamin B12 were added to reduce toxicity , result ing in a significant reduction in toxicities in the pemetrexed/cisplatin arm . CONCLUSION Treatment with pemetrexed plus cisplatin and vitamin supplementation result ed in superior survival time , time to progression , and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma . Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time BACKGROUND Concurrent chemoreirradiation therapy ( CRRT ) offers a therapeutic option for patients with locoregionally recurrent squamous cell carcinoma of the head and neck ( SCCHN ) . We hypothesized that response to induction chemotherapy ( IC ) would improve outcome and predict increased survival . PATIENTS AND METHODS Subjects with recurrent SCCHN not amenable to st and ard therapy were eligible .  IC consisted of two 28-day cycles of gemcitabine and pemetrexed on days 1 and 14 , followed by surgical resection , if appropriate , and /or CRRT consisting of carboplatin , pemetrexed , and single daily fractionated radiotherapy . RESULTS Thirty-five subjects were enrolled , 31 were assessable for response , with 11 responders [ response rate = 35 % ; 95 % confidence interval ( CI ) 19.2 - 54.6 ] . Among 24 subjects who started CRRT , 11 were assessable for radiographic response , 4 complete response , 2 partial response , and 5 progressive disease . Median progression-free survival and overall survival ( OS ) were 5.5 months ( 95 % CI 3.6 - 8.3 ) and 9.5 months ( 95 % CI 7.2 - 15.4 ) , respectively . One-year OS was 43 % ( 95 % CI 26 % to 58 % ) . Subjects who responded to IC had improved survival ( 
    Output:
    
Results for ORR , PFS , and /or OS in patients receiving pemetrexed in combination with other chemotherapeutic agents and /or radiotherapy were promising in the first-line treatment setting .
Pemetrexed was associated with acceptable grade 3 - 4 hematologic toxicities ; it did not result in nonhematologic toxicities commonly seen with cisplatin , such as nephrotoxicity , ototoxicity , and neuropathy .
Results of this review suggest that pemetrexed is an active chemotherapeutic in combination with other agents or radiotherapy in patients with HNC .