title: Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer.
abstract: OBJECTIVE
  For patients with small-cell lung cancer (SCLC), further chemotherapy is routinely considered at relapse after first-line therapy. However, proof of clinical benefit has not been documented.
  
  
  METHODS
  This study randomly assigned patients with relapsed SCLC not considered as candidates for standard intravenous therapy to best supportive care (BSC) alone (n = 70) or oral topotecan (2.3 mg/m2/d, days 1 through 5, every 21 days) plus BSC (topotecan; n = 71).
  
  
  RESULTS
  In the intent-to-treat population, survival (primary end point) was prolonged in the topotecan group (log-rank P = .0104). Median survival with BSC was 13.9 weeks (95% CI, 11.1 to 18.6) and with topotecan, 25.9 weeks (95% CI, 18.3 to 31.6). Statistical significance for survival was maintained in a subgroup of patients with a short treatment-free interval (< or = 60 days). Response to topotecan was 7% partial and 44% stable disease. Patients on topotecan had slower quality of life deterioration and greater symptom control. Principal toxicities with topotecan were hematological: grade 4 neutropenia, 33%; grade 4 thrombocytopenia, 7%; and grade 3/4 anemia, 25%. Comparing topotecan with BSC, infection grade 2 was 14% versus 12% and sepsis 4% versus 1%; other grade 3/4 events included vomiting 3% versus 0, diarrhea 6% versus 0, dyspnea 3% versus 9%, and pain 3% versus 6%. Toxic deaths occurred in four patients (6%) in the topotecan arm. All cause mortality within 30 days of random assignment was 13% on BSC and 7% on topotecan.
  
  
  CONCLUSIONS
  Chemotherapy with oral topotecan is associated with prolongation of survival and quality of life benefit in patients with relapsed SCLC.
authors.affiliation: Royal Marsden Hospital, National Health System Trust, Sutton, Surrey, England. mary.o'brien@rmh.nhs.uk
authors.forename: Mary E R
authors.initials: ME
authors.lastname: O'Brien
authors.forename: Tudor-Eliade
authors.initials: TE
authors.lastname: Ciuleanu
authors.forename: Hristo
authors.initials: H
authors.lastname: Tsekov
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Shparyk
authors.forename: Branka
authors.initials: B
authors.lastname: Cuceviá
authors.forename: Gabor
authors.initials: G
authors.lastname: Juhasz
authors.forename: Nicholas
authors.initials: N
authors.lastname: Thatcher
authors.forename: Graham A
authors.initials: GA
authors.lastname: Ross
authors.forename: Graham C
authors.initials: GC
authors.lastname: Dane
authors.forename: Theresa
authors.initials: T
authors.lastname: Crofts
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000628:therapy*; D010166:Palliative Care; D011788:Quality of Life; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan