title: Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer.
abstract: OBJECTIVE
  This open-label, randomized, multicenter phase III study compared oral topotecan/intravenous cisplatin (TC) with intravenous (IV) etoposide/cisplatin (PE) in patients with untreated extensive-disease small-cell lung cancer (ED-SCLC).
  
  
  METHODS
  A total of 784 patients were randomly assigned to either oral topotecan 1.7 mg/m2/d x 5 with IV cisplatin 60 mg/m2 on day 5 (n = 389) or IV etoposide 100 mg/m2/d x 3 with IV cisplatin 80 mg/m2 on day 1 (n = 395) every 21 days.
  
  
  RESULTS
  Overall survival (primary end point) was similar between groups (P = .48; median: TC, 39.3 weeks v PE, 40.3 weeks). One-year survival was 31% (95% CI, 27% to 36%) in both groups and the difference of -0.03 (95% CI, -6.53 to 6.47) met the predefined criteria of < or = 10% absolute difference for noninferiority of TC relative to PE. Response rates were similar between groups (TC, 63% v PE, 69%). Time to progression was slightly but statistically longer with PE (log-rank P = .02; median: TC, 24.1 weeks v PE, 25.1 weeks). The regimens were similarly tolerable. Grade 3/4 neutropenia occurred more frequently with PE (84% v 59%), whereas grade 3/4 anemia and thrombocytopenia occurred more frequently with TC (38% v 21% and 38% v 23%, respectively). Lung Cancer Symptom Scale scores were statistically better with PE, but the differences were small and of debatable clinical significance.
  
  
  CONCLUSIONS
  Oral topotecan with cisplatin provides similar efficacy and tolerability to the standard (etoposide with cisplatin) in untreated ED-SCLC and may provide greater patient convenience compared with intravenous etoposide and cisplatin.
authors.affiliation: The Center for Cancer Care and Research, St Louis, MO 63141, USA. jeckardt@tcccr.com
authors.forename: John R
authors.initials: JR
authors.lastname: Eckardt
authors.forename: Joachim
authors.initials: J
authors.lastname: von Pawel
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Papai
authors.forename: Antoaneta
authors.initials: A
authors.lastname: Tomova
authors.forename: Valentina
authors.initials: V
authors.lastname: Tzekova
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Crofts
authors.forename: Sarah
authors.initials: S
authors.lastname: Brannon
authors.forename: Paul
authors.initials: P
authors.lastname: Wissel
authors.forename: Graham
authors.initials: G
authors.lastname: Ross
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D005047:Etoposide; D019772:Topotecan; D002945:Cisplatin