title: E5501: phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer.
abstract: OBJECTIVE
  Sequence-dependent improved efficacy of topoisomerase I followed by topoisomerase 2 inhibitors was assessed in a randomized phase II study in extensive-stage small-cell lung cancer (SCLC).
  
  
  METHODS
  Patients with previously untreated extensive-stage SCLC with measurable disease, ECOG performance status of 0-3 and stable brain metastases were eligible. Arm A consisted of topotecan (0.75 mg/m(2)) on days 1, 2 and 3, etoposide (70 mg/m(2)) and cisplatin (20 mg/m(2)) (PET) on days 8, 9 and 10 in a 3-week cycle. Arm B consisted of irinotecan (50 mg/m(2)) and cisplatin (20 mg/m(2)) on days 1 and 8 followed by etoposide (85 mg/m(2) PO bid) on days 3 and 10 (PIE) in a 3-week cycle.
  
  
  RESULTS
  We enrolled 140 patients and randomized 66 eligible patients to each arm. Only 54.5 % of all patients completed the planned maximum 6 cycles. There were grade ≥3 treatment-related adverse events in approximately 70 % of the patients on both arms including 6 treatment-related grade 5 events. The overall response rates (CR + PR) were 69.7 % (90 % CI 59.1-78.9, 95 % CI 57.1-80.4 %) for arm A and 57.6 % (90 % CI 46.7-67.9, 95 % CI 44.8-69.7 %) for arm B. The median progression-free survival and overall survival were 6.4 months (95 % CI 5.4-7.5 months) and 11.9 months (95 % CI 9.6-13.7 months) for arm A and 6.0 months (95 % CI 5.4-7.0 months) and 11.0 months (95 % CI 8.6-13.1 months) for arm B.
  
  
  CONCLUSIONS
  Sequential administration of topoisomerase inhibitors did not improve on the historical efficacy of standard platinum-doublet chemotherapy for extensive-stage SCLC.
authors.affiliation: Emory University, Atlanta, GA, USA.
authors.forename: Taofeek K
authors.initials: TK
authors.lastname: Owonikoko
authors.forename: Joseph
authors.initials: J
authors.lastname: Aisner
authors.forename: Xin Victoria
authors.initials: XV
authors.lastname: Wang
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Dahlberg
authors.forename: Eric H
authors.initials: EH
authors.lastname: Rubin
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Ramalingam
authors.forename: Murugesan
authors.initials: M
authors.lastname: Gounder
authors.forename: Paul Gregory
authors.initials: PG
authors.lastname: Rausch
authors.forename: Rita S
authors.initials: RS
authors.lastname: Axelrod
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage; D059005:Topoisomerase II Inhibitors / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage
chemical_list: D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D000077146:Irinotecan; D019772:Topotecan; D002945:Cisplatin; D002166:Camptothecin