title: Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Leeds General Infirmary, Leeds, UK.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Muers
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Stephens
authors.forename: Patricia
authors.initials: P
authors.lastname: Fisher
authors.forename: Liz
authors.initials: L
authors.lastname: Darlison
authors.forename: Christopher M B
authors.initials: CM
authors.lastname: Higgs
authors.forename: Erica
authors.initials: E
authors.lastname: Lowry
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Nicholson
authors.forename: Mary
authors.initials: M
authors.lastname: O'Brien
authors.forename: Michael
authors.initials: M
authors.lastname: Peake
authors.forename: Robin
authors.initials: R
authors.lastname: Rudd
authors.forename: Michael
authors.initials: M
authors.lastname: Snee
authors.forename: Jeremy
authors.initials: J
authors.lastname: Steele
authors.forename: David J
authors.initials: DJ
authors.lastname: Girling
authors.forename: Matthew
authors.initials: M
authors.lastname: Nankivell
authors.forename: Cheryl
authors.initials: C
authors.lastname: Pugh
authors.forename: Mahesh K B
authors.initials: MK
authors.lastname: Parmar
mesh_terms: D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000145:classification / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires