***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 
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    Input: Background : The incidence of mesothelioma is rising rapidly in the UK . There is no generally accepted st and ard treatment . The BTS recommends active symptom control ( ASC ) . It is not known whether chemotherapy in addition prolongs survival or provides worthwhile palliation with acceptable toxicity . Palliation as recorded by patients has been fully reported for only two regimens : mitomycin , vinblastine , and cisplatin ( MVP ) , and vinorelbine ( N ) . The BTS and collaborators planned to conduct a phase III r and omised trial comparing ASC only , ASC+MVP , and ASC+N in 840 patients with survival as the primary outcome measure . The aim of the present study was to assess the acceptability of the trial design to patients and the suitability of two st and ard  quality of life ( QL ) question naires for mesothelioma . Methods : Collaborating centres registered all new patients with mesothelioma . Those eligible and giving informed consent completed EORTC QLQ-C30+LC13 and FACT-L QL question naires and were r and omised between all three or any two of ( 1 ) ASC only , ( 2 ) ASC+4 cycles of MVP , and ( 3 ) ASC+12 weekly doses of N. Results : During 1 year , 242 patients were registered of whom 109 ( 45 % ) were r and omised ( 55 % of the 197 eligible patients ) . Fifty two patients from 20 centres were r and omised to an option including ASC only . This translates into a rate of 312 per year from 60 centres interested in collaborating in the phase III trial . The EORTC QL question naire was superior to FACT-L in terms of completeness of data and patient preference . Clinical ly relevant palliation was achieved with ASC . Conclusion : The planned phase III trial is feasible BACKGROUND With the rising incidence of malignant mesothelioma ( MM ) , it is important to optimise treatment to control symptoms , maintain quality of life and , if possible , prolong life . We have analysed prospect ively collected data to evaluate a frequently used palliative chemotherapy regimen . PATIENTS AND METHODS Between October 1986 and May 2002 all patients with inoperable pleural mesothelioma were considered for treatment with MVP ( mitomycin C 8 mg/m2 every 6 weeks , vinblastine 6 mg/m2 every 3 weeks and cisplatin 50 mg/m2 every 3 weeks ) chemotherapy . Symptoms were assessed by physician assessment at baseline and after each cycle of chemotherapy . RESULTS One hundred and fifty patients were treated with MVP for mesothelioma . Forty-three per cent had a performance status ( PS ) 2 or worse . The response rate was 15.3 % , with 68.6 % having stable disease . Sixty-nine per cent reported an improvement in symptoms ; in particular there were good responses for pain ( 71 % ) , cough ( 62 % ) and dyspnoea ( 50 % ) . The most common grade 3/4 toxicity was neutropenia ( 22 % ) . Median overall survival was 7 months , with 1-year survival 31 % and 2-year survival 11 % . Median survival for patients with PS 0/1 was 10 months , and was 6 months for patients with PS 2/3 . Poor prognostic factors in univariate analysis included poor PS , weight loss , mixed or sarcomatoid histology , low haemoglobin and high white blood cell count . Excluding pathological subtype , the prognostic significance of poor PS and weight loss were retained in multivariate analysis . CONCLUSIONS Palliation of symptoms in MM is achievable with current cisplatin-based treatments PURPOSE To evaluate the therapeutic impact of a simple combination chemotherapy regimen on symptoms related to malignant mesothelioma . MATERIAL S AND METHODS Between October 1986 and June 1997 , 39 patients with advanced inoperable malignant mesothelioma were treated with palliative MVP ( mitomycin-C 8 mg/m2 q. six weeks , vinblastine 6 mg/m2 q. three weeks and cisplatin 50 mg/m2 q. three weeks ) chemotherapy and assessed for objective response and relief of symptoms . RESULTS Eight of 39 patients ( 20 % ) achieved an objective partial response with a median duration of nine months : only five patients had progression of disease during chemotherapy . Twenty-four of 39 ( 62 % ) had an overall improvement in their symptomology with particularly good responses for pain ( 79 % ) . These benefits were independent of performance status . Resolution of symptoms was achieved in all responding patients within two treatment cycles . There was no statistically significant difference in duration and incidence of symptom response in those patients achieving radiological PR compared with those with no change and more than 60 % of patients with radiological no change obtained useful symptom control . The treatment was well tolerated with only four patients developing grade 3 leucopenia and three with grade 3 nausea . CONCLUSIONS MVP is a well tolerated regimen and its use in malignant mesothelioma provides useful symptomatic benefit . These results should be the basis for further trials of MVP in the management of mesothelioma with symptom control as a principal endpoint PURPOSE To examine the individual and joint effect of various pretreatment clinical characteristics on the survival of patients with mesothelioma treated by the Cancer and Leukemia Group B ( CALGB ) . PATIENTS AND METHODS Between June 1984 and September 1994 , 337 patients with malignant mesothelioma and no prior chemotherapy  were accrued to seven phase II studies conducted by the CALGB which screened the efficacy of 10 treatment regimens or dose levels . The eligibility criteria for all studies were virtually identical . Patient characteristics include the following : age older than 60 years ( 63 % ) ; male ( 83 % ) ; performance status ( PS ) of 0 or 1 ( 81 % ) ; chest pain ( 60 % ) ; definite asbestos exposure ( 62 % ) ; > 5 % weight loss ( 41 % ) ; and pleural involvement ( 94 % ) . Median survival time ( MST ) for the 10 treatment regimens ranged from 3.9 to 9.8 months ( overall=7.2 ; 95 % confidence interval [ CI ] , 6.5 to 8.3 ) , with 1-year survival between 14 % and 50 % ( overall=27 % ; 95 % CI , 23 to 33 % ) . RESULTS Cox survival models and exponential regression trees were used to examine the prognostic importance of pretreatment patient characteristics . Univariate analyses show that patients with poor  Eastern Cooperative Oncology Group PS , chest pain , dyspnea , platelet count ( PLT ) > 400,000/microL , weight loss , serum lactate dehydrogenase ( LDH ) level > 500 IU/L , pleural involvement , low hemoglobin ( HGB ) level , high WBC count , and increasing age over 75 years have a worse prognosis . With decreasing risk ratio , multivariate Cox analyses showed that pleural involvement , LDH > 500 IU/L , poor PS , chest pain , PLT > 400,000/microL , nonepithelial histology , and increasing age older than 75 years jointly predict poor survival . PS was the most important prognostic split in the regression tree . Terminal nodes were amalgamated to form six distinct prognostic subgroups with MST ( 2-year survival ) of 13.9 ( 38 % ) in 36 patients , 9.5 ( 21 % ) in 36 patients , 9.2 ( 10 % ) in 146 patients , 6.5 ( 3 % ) in 33 patients , 4.4 ( 0 % ) in 73 patients , and 1.4 ( 0 % ) in 13 patients ( p<0.0001 ) . CONCLUSIONS The subgroup with the best survival ( MST=13.9 months ) included patients with PS=0 and age younger than 49 years , and patients with PS=0 , age of 49 years or older , and HGB > or = 14.6 . The worst survival ( MST= 1.4 months ) occurred for patients with PS= 1/2 and WBC > or = 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 PURPOSE This report describes the data and analysis leading to the approval of pemetrexed ( LY 231514 , MTA , Alimta , Eli Lilly and Co. , Indianapolis , IN ) by the U.S. Food and Drug Administration ( FDA ) of a New Drug Application for the treatment of malignant pleural mesothelioma ( MPM ) . EXPERIMENTAL DESIGN The FDA review of the efficacy and safety of pemetrexed assessed in a r and omized clinical trial of 448 patients with unresectable MPM comparing pemetrexed plus cisplatin with cisplatin alone , as well as pre clinical pharmacology and chemistry data , are described . The basis for marketing approval is discussed . RESULTS In one r and omized , single-blind , multicenter international trial , 226 patients were r and omized to the pemetrexed and cisplatin arm and 222 patients were r and omized to cisplatin alone .  Median survival times were 12.1 months for pemetrexed and cisplatin and 9.3 months for cisplatin ( P = 0.021 ; hazard ratio , 0.766 ; 95 % confidence interval , 0.61 - 0.96 ) . Myelosuppression , predominantly neutropenia , was the most common toxicity of pemetrexed plus cisplatin . Other common adverse events were fatigue , leucopenia , nausea , dyspnea , vomiting , chest pain , anemia , thrombocytopenia , and anorexia . CONCLUSIONS Pemetrexed in combination with cisplatin was approved by the FDA on February 4 , 2004 for the treatment of patients with MPM whose disease is either unresectable or who are otherwise not c and i date s for curative surgery . The recommended dose of pemetrexed is 500 mg/m(2 ) intra venous infusion over 10 minutes on day 1 of each 21-day cycle in combination with 75 mg/m(2 ) cisplatin infused over 2 hours beginning 30 minutes after the pemetrexed infusion . Patients must receive oral folic acid and vitamin B(12 ) injections before the start and during therapy to reduce severe toxicities . Patients should also receive corticosteroids with the chemotherapy to decrease the incidence of skin rash . Approval was based on a demonstration of survival improvement in a single r and omized trial . Response rates and time to tumor progression were not included in product labeling because of inconsistencies in assessment s among the investigators , independent radiologic review ers , and the FDA , reflecting the difficulty of radiographic assessment s in malignant mesothelioma . Complete prescribing information is available on the FDA Web site at http://www . fda .gov/cder/approval/index.htm PURPOSE Multitargeted antifolate ( MTA ; LY231514 ) has broad pre clinical antitumor activity and inhibits a variety of intracellular enzymes involved in the folate pathways . This study was design ed to ( 1 ) determine the maximum-tolerated dose ( MTD ) , dose-limiting toxicities ( DLT ) , and pharmacokinetics of M 
    Output:
    
Pemetrexed disodium in combination with cisplatin and with folic acid and vitamin B(12 ) supplementation may improve survival when used in combination with cisplatin in good performance status patients .