title: Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial.
abstract: OBJECTIVE
  Ifosfamide, carboplatin, etoposide, and vincristine, alone and in combination, are highly active against small-cell lung cancer (SCLC). This trial was designed to investigate whether survival could be improved by a regimen of all four drugs (ICE-V) compared with standard chemotherapy in patients with SCLC and good performance status, and to assess the patients' quality of life (QL).
  
  
  METHODS
  Patients were randomly assigned to receive six cycles of either ICE-V at 4-week intervals without dose reduction or standard chemotherapy administered according to local practice. The recommended standard control regimens were cyclophosphamide, doxorubicin, and etoposide; and cisplatin and etoposide.
  
  
  RESULTS
  A total of 402 patients were randomly assigned, and 350 (87%) patients have died. Overall survival was longer in the ICE-V group (hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P = .0049), median survival was 15.6 months in the ICE-V group and 11.6 months in the control group, and 2-year survival rates were 20% and 11%, respectively. There was no evidence that the relative survival benefit for ICE-V was less in extensive-stage than in limited-stage patients. An increased rate of septicemia was reported in the ICE-V group (15% v 7% in the control group), but this did not result in an increase in reported treatment-related deaths (four patients [2%] in both groups). The findings on QL were broadly similar in both groups, with some benefit in favor of ICE-V.
  
  
  CONCLUSIONS
  Compared with standard chemotherapy, the ICE-V regimen improves overall survival without QL penalties, despite an increased but manageable level of toxicity.
authors.affiliation: Medical Research Council Clinical Trials Unit, London NW1 2DA, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Thatcher
authors.forename: Wendi
authors.initials: W
authors.lastname: Qian
authors.forename: Peter I
authors.initials: PI
authors.lastname: Clark
authors.forename: Penelope
authors.initials: P
authors.lastname: Hopwood
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Sambrook
authors.forename: Robert
authors.initials: R
authors.lastname: Owens
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Stephens
authors.forename: David J
authors.initials: DJ
authors.lastname: Girling
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D006113:United Kingdom / Q000453:epidemiology; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide