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document
Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma ( MS01 ) : a multicentre randomised trial . BACKGROUND Malignant pleural mesothelioma is almost always fatal , and few treatment options are available . Although active symptom control ( ASC ) has been recommended for the management of this disease , no consensus exists for the role of chemotherapy . We investigated whether the addition of chemotherapy to ASC improved survival and quality of life . METHODS 409 patients with malignant pleural mesothelioma , from 76 centres in the UK and two in Australia , were randomly assigned to ASC alone ( treatment could include steroids , analgesic drugs , bronchodilators , palliative radiotherapy [ n=136 ] ) ; to ASC plus MVP ( four cycles of mitomycin 6 mg/m2 , vinblastine 6 mg/m2 , and cisplatin 50 mg/m2 every 3 weeks [ n=137 ] ) ; or to ASC plus vinorelbine ( one injection of vinorelbine 30 mg/m2 every week for 12 weeks [ n=136 ] ) . Randomisation was done by minimisation , with stratification for WHO performance status , histology , and centre . Follow-up was every 3 weeks to 21 weeks after randomisation , and every 8 weeks thereafter . Because of slow accrual , the two chemotherapy groups were combined and compared with ASC alone for the primary outcome of overall survival . Analysis was by intention to treat . This study is registered , number ISRCTN54469112 . FINDINGS At the time of analysis , 393 ( 96 % ) patients had died ( ASC 132 [ 97 % ] , ASC plus MVP 132 [ 96 % ] , ASC plus vinorelbine 129 [ 95 % ] ) . Compared with ASC alone , we noted a small , non-significant survival benefit for ASC plus chemotherapy ( hazard ratio [ HR ] 0.89 [ 95 % CI 0.72-1.10 ] ; p=0.29 ) . Median survival was 7.6 months in the ASC alone group and 8.5 months in the ASC plus chemotherapy group . Exploratory analyses suggested a survival advantage for ASC plus vinorelbine compared with ASC alone ( HR 0.80 [ 0.63-1.02 ] ; p=0.08 ) , with a median survival of 9.5 months . There was no evidence of a survival benefit with ASC plus MVP ( HR 0.99 [ 0.78-1.27 ] ; p=0.95 ) . We observed no between-group differences in four predefined quality-of-life subscales ( physical functioning , pain , dyspnoea , and global health status ) at any of the assessments in the first 6 months . INTERPRETATION The addition of chemotherapy to ASC offers no significant benefits in terms of overall survival or quality of life . However , exploratory analyses suggested that vinorelbine merits further investigation .
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Intervention_Pharmacological
ASC
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Intervention_Pharmacological
steroids
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Intervention_Pharmacological
analgesic drugs
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Intervention_Pharmacological
bronchodilators
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Intervention_Pharmacological
palliative radiotherapy
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Intervention_Pharmacological
ASC plus MVP
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Intervention_Pharmacological
mitomycin
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Intervention_Pharmacological
vinblastine
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Intervention_Pharmacological
cisplatin
35746
Intervention_Pharmacological
ASC plus vinorelbine
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Intervention_Pharmacological
vinorelbine
35748
Outcome_Mortality
survival
35749
Outcome_Physical
quality of life
35750
Outcome_Mortality
died
35751
Outcome_Mortality
non-significant survival benefit
35752
Outcome_Mortality
Median survival
35753
Outcome_Mortality
survival advantage
35754
Outcome_Mortality
median survival
35755
Outcome_Mortality
survival benefit
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Outcome_Physical
quality-of-life subscales ( physical functioning , pain , dyspnoea , and global health status )
35757
Outcome_Mortality
survival
35758
Outcome_Mental
or
35759
Outcome_Physical
quality of life