***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: There is no effective treatment for malignant mesothelioma . Control is rarely achieved with surgery , radiotherapy and /or chemotherapy , and none of these treatment modalities demonstrated a clear survival benefit , over no treatment , in two major retrospective review s [ 1,2 ] . Most phase II single-agent chemotherapy trials in malignant mesothelioma have been conducted in small numbers of patients . Only doxorubicin , cisplatin , vindesine , 5-fluorouracil , detorubicin and diaziquone have been individually studied in phase II trials with more than 20 patients , and only doxorubicin and cisplatin yielded a confirmed 10 % or better objective response rate [ 3 ] . Various combinations of doxorubicin , cisplatin , cyclophosphamide and 5-fluorouracil result in about a 20~ objective response rate [ 3 ] . The need for adequate phase II trials of other chemotherapeutic agents in mesothelioma is obvious . 5,6-Dihydro-5-azacytidine ( DHAC ) was synthesized to overcome 5-azacytidine 's limitations of unacceptable toxicity and insolubility in an aqueous carrier [ 4 ] . DHAC is active in a number of tumor models , including the murine L1210 and P388 leukemia , and solid tumor models including human MX-1 mammary xenograft , murine CD8F1 mammary tumor and the subcutaneously implanted colon 38 tumor [ 5 ] . Its mode of action is similar to that of 5-azacytidine : it is incorporated into the nuclear RNA and inhibits transcription of ribosomal and nuclear RNA , result ing in diminished DNA and protein synthesis [ 6 ] . In two clinical trials of DHAC in non-small cell lung carcinoma , one phase I and the other phase II , chest pain was the dose-limiting toxicity , but the myelosuppression , liver toxicity , hypotension and nausea/vomiting attendant to the administration of 5-azacytidine were not observed [ 6,7 ] . A 32~ response rate was observed in malignant mesothelioma treated with a combination of 5-azacytidine and doxorubicin [ 8 ] . Although 5-azacytidine has not been adequately studied in the treatment of malignant mesothelioma , the foregoing study suggests possible antitumor activity . Availability of DHAC , as a stable and less toxic congener of 5-azacytidine , prompted current phase II study in this otherwise very refractory malignancy BACKGROUND The use of doxorubicin has shown some activity in malignant mesothelioma but prolonged administration is hampered by cardiotoxicity .  Caelyx , a new liposomal and pegylated form of doxorubicin has shown a better pharmacokinetic and toxic profile then doxorubicin . In a phase II study , the efficacy and toxicity of Caelyx was tested in previously untreated patients with malignant pleural mesothelioma . PATIENTS AND METHODS Thirty-three patients who had measurable or evaluable histologically confirmed malignant pleural mesothelioma were included in the study .  Caelyx ( 45 mg/m2 ) was given i.v . on outpatient base every four weeks for nine cycles or till progression or unacceptable toxicity occurred . RESULTS Of the 33 patients , 32 were evaluable for toxicity and 31 for response . Two patients had a partial response ( 6 % , 95 % confidence interval : 0.2%-20.2 % ) . The median survival was 13 months . Forty percent of the patients received > 6 cycles . Toxicity was mild with palmar plantar erythrodysesthesia being most pronounced ( 62 % grade 1 - 2 , 6 % grade 3 ) and of limited duration . Ten percent of patients had grade 3 anemia and 3 % grade 3 thrombocytopenia . Two patients ( 6 % ) had grade 3 or 4 cardiac toxicity , which was not drug related . CONCLUSION At the prescribed dose , single agent Caelyx is well tolerated but its activity in chemotherapy-naive mesothelioma patients does not warrant further investigation as a single agent The EORTC Lung Cancer Cooperative Group undertook a phase II study of paclitaxel in 25 chemotherapy-naive patients with malignant pleural mesothelioma .  Paclitaxel was given intravenously at a dose of 200 mg m-2 as a 3 h infusion every 3 weeks , after st and ard premedication with corticosteroids and antihistamines . This regimen was well tolerated , with < 4 % of cycles result ing in severe toxicity . No major objective responses were observed and ten patients had stable disease . Median survival time was 39 weeks and the 1 year survival rate was 30 % . In conclusion , paclitaxel at the dose and schedule investigated in this trial had no major activity in the treatment of malignant pleural mesothelioma Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6 % ( 95 % CI 26.2–69.0 % ) response rate with symptom improvement in responding patients . Here we confirm these findings in a multicentre setting , and assess the effect of this treatment on quality of life and pulmonary function .  Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m−2 i.v . day 1 and gemcitabine 1000 mg m−2 i.v . days 1 , 8 , and 15 of a 28 day cycle for a maximum of six  cycles . Quality of life and pulmonary function were assessed at each cycle . The best response achieved in 52 assessable patients was : partial response , 17 ( 33 % , 95 % CI 20–46 % ) ; stable disease , 31 ( 60 % ) ; and progressive disease , four ( 8 % ) . The median time to disease progression was 6.4 months , median survival from start of treatment 11.2 months , and median survival from diagnosis 17.3 months . Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients . Major toxicities were haematological , limiting the mean relative dose intensity of gemcitabine to 75 % . This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting . Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life PURPOSE The aim of this open-label phase II study was to evaluate the activity of raltitrexed ( Tomudex ; AstraZeneca , Cergy , France ) and oxaliplatin combination therapy in patients with diffuse malignant pleural mesothelioma . PATIENT AND METHODS s : Fifteen pretreated and 55 chemotherapy-naive patients ( median age , 60 years ; World Health Organization performance status of < or = 2 ) were enrolled . Most patients ( 66 % ) had advanced disease . Patients received raltitrexed 3 mg/m2 followed by oxaliplatin 130 mg/m2 every 3 weeks . RESULTS Twenty-four patients ( 34 % ) were classified as having a poor prognosis . In the overall study population , 14 patients ( 20 % ) had a partial response , and 32 patients ( 46 % ) had stable disease . The symptomatic response rates were as follows : shortness of breath , 36 % ; pain , 30 % ; activity , 23 % ; appetite , 21 % ; and asthenia , 20 % . Median time to disease progression was 18 weeks ( 95 % confidence interval [ CI ] , 13 to 22 weeks ) . In chemotherapy-naive patients , median survival was 31 weeks ( 95 % CI , 23 to 40 weeks ) from the start of treatment and 49 weeks ( 95 % CI , 40 to 52 weeks ) from diagnosis of mesothelioma . In pretreated patients , median survival was 44 weeks ( 95 % CI , 24 to 40 weeks ) from the start of treatment and 226 weeks ( 95 % CI , 63 to 292 weeks ) from the diagnosis of mesothelioma . Overall 1-year survival was 26 % ( 95 % CI , 15.5 % to 36.4 % ) , survival was 22 % ( 95 % CI , 10.9 % to 33.2 % ) in chemotherapy-naive patients and 40 % ( 95 % CI , 15.2 % to 64.8 % ) in pretreated patients . Hematologic toxicity was mild , and there was no alopecia . The most common adverse events were asthenia , nausea/vomiting , and paraesthesia , and no treatment-related deaths were reported . CONCLUSION The raltitrexed and oxaliplatin combination is an active outpatient regimen in malignant mesothelioma and has an acceptable tolerability profile Twenty‐six symptomatic patients with diffuse malignant pleural mesothelioma ( DMPM ) were enrolled in a Phase II Italian Lung Cancer Task Force ( FONICAP ) study to assess the activity and toxicity of doxorubicin and cisplatin combination chemotherapy . The drug schedule was as follows : 60 mg/m2 of doxorubicin and 60 mg/m2 of cisplatin both given intravenously ( IV ) on day 1 every 3 to 4 weeks . Of the 24 evaluable patients , 6 objective partial responses ( 25 % ; 95 % confidence limits , 9.77 % to 46.71 % ) were observed . Twelve of 24 patients ( 50 % ) , including 6 with no radiologic evidence of response , had a clinical improvement as demonstrated by an objective reduction of symptom or performance status scores along treatment . The overall median survival time was 10 months . Toxicity was mild and dose reductions or suspensions were not required . The combination of doxorubicin and cisplatin is effective and well tolerated . It might be considered for palliation of symptomatic patients with DMPM PURPOSE We conducted a phase III trial to determine whether first-line treatment with raltitrexed , a thymidine synthase inhibitor , and cisplatin results in superior outcome compared with cisplatin alone in patients with malignant pleural mesothelioma ( MPM ) . PATIENTS AND METHODS Eligible patients with histologically proven advanced MPM , not pretreated with chemotherapy , WHO performance status ( PS ) 0 to 2 , and adequate hematological , renal , and hepatic function were r and omly assigned to receive cisplatin 80 mg/m2 IV on day 1 , alone ( arm A ) or combined with raltitrexed 3 mg/m2 ( arm B ) . In patients with measurable disease , response was monitored using the Response Evaluation Criteria in Solid Tumors criteria . Health related quality of life ( HRQOL ) was measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 and Lung Module ( QLQ-LC13 ) . RESULTS Two hundred fifty patients were r and omized : 80 % male ; median age , 58 years ; and WHO PS , 0 , 1 , 2 in 25 , 62 , and 13 % of cases , respectively . There were no toxic deaths . The main grade 3 or 4 toxicities observed were neutropenia and emesis , reported twice as often in the combination arm . Among 213 patients with measurable disease , response rate was 13.6 % ( arm A ) versus 23.6 % ( arm B ; P = .056 ) . No difference in HRQOL was observed on any of the scales . Median overall and 1-year survival in arms A and B were 8.8 ( 95 % CI , 7.8 to 10.8 ) v 11.4 months ( 95 % CI , 10.1 to 15 ) , respectively , and 40 % v 46 % , respectively ( P = .048 ) . CONCLUSION A combination of raltitrexed and cisplatin improves overall survival compared with cisplatin alone . This study confirms that a combination of cisplatin and an antifolate is superior to cisplatin alone in patients with MPM , without harmful effect on HRQOL PURPOSE To assess the tolerance , toxicity , and antitumoral activity of the weekly combination of cisplatin ( CDDP ) and interferon alfa-2a ( IFNalpha2a ) in advanced diffuse malignant mesothelioma ( DMM ) . PATIENTS AND METHODS Twenty-six patients with DMM ( 23 pleural and three peritoneal ) , previously untreated , were enrolled onto this study between August 1991 and December 1992 . All patients had measurable disease defined by computed tomographic ( CT ) scan and diagnostic confirmation by histopathology review panel .  IFNalpha2a ( 3 x 10(6 ) IU subcutaneously on days 1 to 4 ) and CDDP ( 60 mg/m2/wk on day 2 ) were given weekly . Initially planned as a 5-weeks-on/3-weeks-off treatment cycle , poor patient tolerance observed in the first 12 patients treated ( group A ) led to schedule adaptation with a shorter treatment sequence and prolongation of the rest period ( 4 weeks on/4 weeks off ) in the following 14 patients ( group B ) . At least two cycles were 
    Output:
    
The pooled response rates from phase II trials suggest that response rates with combination chemotherapy are higher than with single agents .
There is good evidence to recommend chemotherapy with pemetrexed and cisplatin for adult patients with symptomatic advanced malignant pleural mesothelioma .