title: Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group.
abstract: OBJECTIVE
  To assess activity and toxicity of topotecan in previously treated small-cell lung cancer (SCLC) patients.
  
  
  METHODS
  Patients with measurable SCLC, progressive after one first-line regimen, were eligible for the study. Two groups of patients were selected: (1) patients who failed first-line treatment < or = 3 months from chemotherapy discontinuation (refractory group); and (2) patients who responded to first-line treatment and progressed greater than 3 months after chemotherapy discontinuation (sensitive group). Topotecan was administered as a 30-minute daily infusion at a dose of 1.5 mg/m2 for 5 consecutive days, every 3 weeks.
  
  
  RESULTS
  One hundred one patients were entered onto the study and 403 courses were administered. Ninety-two patients (47 refractory and 45 sensitive) were eligible and assessable for response. Among refractory patients, there were two partial responses (PRs) and one complete response (CR), for an overall response rate of 6.4% (95% confidence interval [CI], 1.3% to 17.6%), whereas in the sensitive group, there were 11 PRs and six CRs, for an overall response rate of 37.8% (95% CI, 23.8% to 53.5%). Overall median duration of response was 7.6 months. Median survival was 5.4 months; median survival of refractory patients was 4.7 months, whereas that of sensitive patients was 6.9 months (P = .002). Median survival of responding patients was 12.5 months. Toxicity was mainly hematologic. Leukopenia, although short-lived, was universal, with grade III and IV neutropenia occurring in 28% and 46.8% of cycles, respectively. Nonhematological toxicity was mild. Fatigue/malaise was reported in 39.3% of cycles and transient elevation of liver enzymes in 17%.
  
  
  CONCLUSIONS
  Topotecan has significant activity in SCLC, particularly in patients sensitive to prior chemotherapy, with predictable and manageable toxicity. The incorporation of topotecan in combination chemotherapy regimens for future treatment of SCLC is warranted.
authors.affiliation: Department of Medical Oncology I, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ardizzoni
authors.forename: H
authors.initials: H
authors.lastname: Hansen
authors.forename: P
authors.initials: P
authors.lastname: Dombernowsky
authors.forename: T
authors.initials: T
authors.lastname: Gamucci
authors.forename: S
authors.initials: S
authors.lastname: Kaplan
authors.forename: P
authors.initials: P
authors.lastname: Postmus
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
authors.forename: B
authors.initials: B
authors.lastname: Schaefer
authors.forename: J
authors.initials: J
authors.lastname: Wanders
authors.forename: J
authors.initials: J
authors.lastname: Verweij
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000556:secondary; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D012074:Remission Induction; D016019:Survival Analysis; D019772:Topotecan
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan; D002166:Camptothecin