title: Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life.
abstract: OBJECTIVE
  Chemotherapy for non-small-cell lung cancer (NSCLC) remains controversial. We describe the two largest reported, randomized, parallel trials designed to determine whether the addition of chemotherapy influences duration and quality of life in localized, unresectable (mitomycin, ifosfamide, cisplatin [MIC]1 trial) and extensive (MIC2 trial) disease.
  
  
  METHODS
  Ambulatory patients with NSCLC, aged 75 years or younger, with localized disease, were randomized in MIC1 to receive up to four cycles of chemotherapy (CT: mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) every 21 days, followed by radical radiotherapy (CT + RT) or radiotherapy (RT) alone. Extensive-stage patients were randomized in MIC2 to identical chemotherapy plus palliative care (CT + PC) or palliative care (PC) alone. Short-term change in quality of life (QOL) was assessed in a subgroup of patients. Data from the two trials were combined to allow multivariate and stratified survival analyses.
  
  
  RESULTS
  Seven hundred ninety-seven eligible patients were randomized, 446 in MIC1 and 351 in MIC2. MIC CT improved survival in both trials (significantly in MIC2). The median survival time in MIC1 was 11.7 months (CT + RT) versus 9.7 months (RT alone) (P =.14); whereas in MIC2, median survival time was 6.7 months (CT + PC) compared with 4. 8 months (PC alone) (P =.03). QOL, assessed in 134 patients from start of trial to week 6, showed improvement with chemotherapy and deterioration with standard treatment. In the combined analysis of 797 randomized patients, the positive effect of MIC on survival was significant overall (P =.01) and after adjusting for prognostic factors (P =.01).
  
  
  CONCLUSIONS
  MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL.
authors.affiliation: Queen Elizabeth Centre for the Treatment of Cancer, University Hospital Birmingham, Birmingham, United Kingdom. michael.cullen@universtity-b.wmids.nhs.uk
authors.forename: M H
authors.initials: MH
authors.lastname: Cullen
authors.forename: L J
authors.initials: LJ
authors.lastname: Billingham
authors.forename: C M
authors.initials: CM
authors.lastname: Woodroffe
authors.forename: A D
authors.initials: AD
authors.lastname: Chetiyawardana
authors.forename: N H
authors.initials: NH
authors.lastname: Gower
authors.forename: R
authors.initials: R
authors.lastname: Joshi
authors.forename: D R
authors.initials: DR
authors.lastname: Ferry
authors.forename: R M
authors.initials: RM
authors.lastname: Rudd
authors.forename: S G
authors.initials: SG
authors.lastname: Spiro
authors.forename: J E
authors.initials: JE
authors.lastname: Cook
authors.forename: C
authors.initials: C
authors.lastname: Trask
authors.forename: E
authors.initials: E
authors.lastname: Bessell
authors.forename: C K
authors.initials: CK
authors.lastname: Connolly
authors.forename: J
authors.initials: J
authors.lastname: Tobias
authors.forename: R L
authors.initials: RL
authors.lastname: Souhami
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D011379:Prognosis; D011788:Quality of Life; D016019:Survival Analysis
chemical_list: D016685:Mitomycin; D002945:Cisplatin; D007069:Ifosfamide