title: Early compared with late radiotherapy in combined modality treatment for limited disease small-cell lung cancer: a London Lung Cancer Group multicenter randomized clinical trial and meta-analysis.
abstract: OBJECTIVE
  To replicate an earlier National Cancer Institute of Canada (NCIC) trial that examined the effect on survival of the timing of thoracic radiotherapy (TRT) in patients with limited disease small-cell lung cancer (SCLC).
  
  
  METHODS
  Patients received three cycles of cyclophosphamide, doxorubicin, and vincristine alternating with three cycles of etoposide and cisplatin. Three hundred twenty five chemotherapy- and radiotherapy-naïve patients were randomly assigned to either early TRT administered concurrently in the second cycle or late TRT administered concurrently with the sixth cycle; the dose was 40 Gy in 15 fractions over 3 weeks.
  
  
  RESULTS
  TRT was received by 92% and 82% of patients in the early and late arms, respectively (P = .01). Sixty-nine percent of patients in the early arm received all six courses of chemotherapy compared with 80% in the late arm (P = .003). There was no evidence of a survival difference; median overall survival time was 13.7 and 15.1 months in the early and late arms, respectively (P = .23). In a meta-analysis of all eight trials that compared early and late TRT, there were three in which the proportion of patients who completed their planned chemotherapy was similar between the TRT arms (hazard ratio [HR] = 0.73; 95% CI, 0.62 to 0.86) and five in which proportionally fewer patients in the early TRT arm completed their chemotherapy (HR = 1.06; 95% CI, 0.97 to 1.17).
  
  
  CONCLUSIONS
  This study failed to show a survival advantage for early TRT with chemotherapy in limited-stage SCLC, unlike the NCIC trial. However, the results of a meta-analysis suggest that it is essential to ensure that the delivery of chemotherapy is optimal when administered with early TRT.
authors.affiliation: University College Hospitals Trust, London, United Kingdom.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Spiro
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: James
authors.forename: Robin M
authors.initials: RM
authors.lastname: Rudd
authors.forename: Colin W
authors.initials: CW
authors.lastname: Trask
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Tobias
authors.forename: Michael
authors.initials: M
authors.lastname: Snee
authors.forename: David
authors.initials: D
authors.lastname: Gilligan
authors.forename: Philip A
authors.initials: PA
authors.lastname: Murray
authors.forename: Mary Carmen
authors.initials: MC
authors.lastname: Ruiz de Elvira
authors.forename: Katy M
authors.initials: KM
authors.lastname: O'Donnell
authors.forename: Nicole H
authors.initials: NH
authors.lastname: Gower
authors.forename: Peter G
authors.initials: PG
authors.lastname: Harper
authors.forename: Allan K
authors.initials: AK
authors.lastname: Hackshaw
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000517:prevention & control / Q000556:secondary; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008131:London; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin