title: Phase II trial of oral topotecan and intravenous carboplatin with G-CSF support in previously untreated patients with extensive stage small cell lung cancer: A North Central Cancer Treatment Group Study.
abstract: OBJECTIVE
  The objective of this study was to evaluate the response rate and toxicities of the combination of oral topotecan and carboplatin in patients with untreated extensive stage small cell lung cancer (ES-SCLC). Previous studies have suggested improved outcomes with a topoisomerase I inhibitor in combination with a platinum agent.
  
  
  METHODS
  Twenty-six patients with previously untreated, ES-SCLC were evaluable in this phase II trial. All patients received oral topotecan 2.0 mg/m per day on days 1 through 5 and carboplatin at an area under curve of 5 on day 5. Treatment was repeated every 21 days up to a total of 6 cycles. All patients received G-CSF.
  
  
  RESULTS
  There were no complete responses and 16 partial responses, for an overall response rate of 62% (95% CI: 41-80). Median time to progression was 6.0 months (95% CI: 4-8), with a median overall survival of 12 months (95% CI: 8-16). This study was closed to accrual early with 26 of a planned 39 patients enrolled because of grade 5 adverse events in 4 (15%) patients (3 neutropenic infections, 1 sudden cardiac death). Eighty-five percent of patients experienced grade 3 or higher hematologic events. The most common severe nonhematologic events included diarrhea, vomiting, dyspnea, hypoxia, and hypotension.
  
  
  CONCLUSIONS
  Although this drug regimen has activity as first-line therapy in ES-SCLC, it is associated with excessive hematologic toxicity, which occurred in spite of growth factor support. Despite promising survival estimates, this particular combination and dose level of oral topotecan and carboplatin cannot be recommended.
authors.affiliation: Mayo Clinic and Mayo Foundation, Rochester, MN, USA. abryce@ccsb.org
authors.forename: Alan H
authors.initials: AH
authors.lastname: Bryce
authors.forename: Bassam
authors.initials: B
authors.lastname: Mattar
authors.forename: Shauna L
authors.initials: SL
authors.lastname: Hillman
authors.forename: Alex A
authors.initials: AA
authors.lastname: Adjei
authors.forename: John W
authors.initials: JW
authors.lastname: Kugler
authors.forename: Kendrith
authors.initials: K
authors.lastname: Rowland
authors.forename: Donald B
authors.initials: DB
authors.lastname: Wender
authors.forename: Gamini
authors.initials: G
authors.lastname: Soori
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: James R
authors.initials: JR
authors.lastname: Jett
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D013997:Time Factors; D019772:Topotecan / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D019772:Topotecan; D016190:Carboplatin