title: Phase II study of topotecan in metastatic non-small-cell lung cancer.
abstract: OBJECTIVE
  Topotecan is an inhibitor of topoisomerase I that has shown preclinical activity against non-small-cell lung cancer (NSCLC). This phase II study was designed to determine the clinical activity and toxicity spectrum of topotecan in untreated patients with metastatic NSCLC.
  
  
  METHODS
  Twenty previously untreated patients received topotecan every 21 days at the dose of 2 mg/m2/d intravenously (IV) for 5 days for two cycles, at which point response was assessed. Patients with either clinical response or stable disease (SD) received additional cycles of the drug until toxicity developed or disease progression (PRG) occurred.
  
  
  RESULTS
  This study was designed to enter 30 patients. However, because no clinical responses were seen in the first 20 patients entered onto the study, the early-stopping rule was invoked and patient accrual was halted. Eleven patients (55%) had SD on topotecan, and nine (45%) had PRG. Toxicity included neutropenia and rash. The median survival duration for all patients was 7.6 months.
  
  
  CONCLUSIONS
  We observed no objective clinical responses despite producing high-grade neutropenia. Phase II trials of topotecan using different schedules or higher doses supported by growth factors may clarify the role of topotecan in the treatment of NSCLC. The combination of topotecan with cisplatin and topoisomerase II inhibitors such as etoposide should be explored. Finally, the median survival duration of 7.6 months for 20 patients treated with an agent that failed to produce any obvious clinical responses compares favorably to the survival obtained with combinations of existing agents. This supports the further study of novel compounds in this clinical setting.
authors.affiliation: Division of Clinical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Lynch
authors.forename: L
authors.initials: L
authors.lastname: Kalish
authors.forename: G
authors.initials: G
authors.lastname: Strauss
authors.forename: A
authors.initials: A
authors.lastname: Elias
authors.forename: A
authors.initials: A
authors.lastname: Skarin
authors.forename: L N
authors.initials: LN
authors.lastname: Shulman
authors.forename: M
authors.initials: M
authors.lastname: Posner
authors.forename: E
authors.initials: E
authors.lastname: Frei
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019772:Topotecan; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan; D002166:Camptothecin