title: Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer.
abstract: OBJECTIVE
  This Phase III study was performed to determine whether twice-daily (b.i.d.) radiotherapy (RT) resulted in better survival than once-daily (q.d.) RT for patients with limited-stage small-cell lung cancer (LD-SCLC).
  
  
  METHODS
  A total of 310 patients with LD-SCLC initially received three cycles of etoposide and cisplatin. Subsequently, the 261 patients without significant progression were randomized to two cycles of etoposide and cisplatin plus either q.d. RT (50.4 Gy in 28 fractions) or split-course b.i.d. RT (24 Gy in 16 fractions, a 2.5-week break, and 24 Gy in 16 fractions) to the chest. Patients then received a sixth cycle of etoposide and cisplatin followed by prophylactic cranial RT.
  
  
  RESULTS
  Follow-up ranged from 4.6 to 11.9 years (median, 7.4 years). The median survival and 5-year survival rate from randomization was 20.6 months and 21% for patients who received q.d. RT compared with 20.6 months and 22% for those who received b.i.d. RT (p = 0.68), respectively. No statistically significant differences were found in the rates of progression (p = 0.68), intrathoracic failure (p = 0.45), in-field failure (p = 0.62), or distant failure (p = 0.82) between the two treatment arms. No statistically significant difference was found in the overall rate of Grade 3 or worse (p = 0.83) or Grade 4 or worse toxicity (p = 0.95). Grade 3 or worse esophagitis (p = 0.05) was more common in the b.i.d. arm. Grade 5 toxicity occurred in 4 (3%) of 130 patients who received b.i.d. RT compared with 0 (0%) of 131 who received q.d. RT (p = 0.04).
  
  
  CONCLUSIONS
  Although this study did not demonstrate an advantage to split-course b.i.d. RT, the long-term survival was favorable, likely reflecting the positive influences of concurrent combined modality therapy and prophylactic cranial RT.
authors.affiliation: Mayo Clinic and Mayo Foundation, Rochester, MN, USA. sschild@mayo.edu
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schild
authors.forename: James A
authors.initials: JA
authors.lastname: Bonner
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Shanahan
authors.forename: Burke J
authors.initials: BJ
authors.lastname: Brooks
authors.forename: Randolph S
authors.initials: RS
authors.lastname: Marks
authors.forename: Susan M
authors.initials: SM
authors.lastname: Geyer
authors.forename: Shauna L
authors.initials: SL
authors.lastname: Hillman
authors.forename: Gist H
authors.initials: GH
authors.lastname: Farr
authors.forename: Henry D
authors.initials: HD
authors.lastname: Tazelaar
authors.forename: James E
authors.initials: JE
authors.lastname: Krook
authors.forename: Francois J
authors.initials: FJ
authors.lastname: Geoffroy
authors.forename: Muhammad
authors.initials: M
authors.lastname: Salim
authors.forename: Robert M
authors.initials: RM
authors.lastname: Arusell
authors.forename: James A
authors.initials: JA
authors.lastname: Mailliard
authors.forename: Paul L
authors.initials: PL
authors.lastname: Schaefer
authors.forename: James R
authors.initials: JR
authors.lastname: Jett
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects; D016019:Survival Analysis
chemical_list: D005047:Etoposide; D002945:Cisplatin