title: Phase I and pharmacologic study of weekly bolus topotecan for advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  We conducted a phase I trial of the topoisomerase I inhibitor topotecan for the purpose of determining the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of topotecan when administered weekly to patients with advanced non-small-cell lung cancer.
  
  
  METHODS
  Twelve patients with stage IIIB or IV disease were treated with topotecan by 30-minute intravenous infusion on days 1, 8, and 15 every 4 weeks. The dose was escalated in 2-mg/m2 increments from the starting dose of 4 mg/m2 until the MTD was reached. After the MTD had been reached in previously treated patients, chemotherapy-naive patients were enrolled for treatment at that dose, and the dose was escalated to estimate the MTD in the treatment-naive group.
  
  
  RESULTS
  The MTD of topotecan was determined to be 6 mg/m2 in the previously treated group and 8 mg/m2 in the chemotherapy-naive group. All 3 previously treated patients experienced DLT at the 6-mg/m2 dose level. Although only 1 of the 3 previously treated patients experienced DLT (grade 4 neutropenia for > or = 3 days) at the 8-mg/m2 dose level, skipping the topotecan dose on day 15 because of neutropenia was reported in 2 patients. Anorexia and general fatigue were the common nonhematologic toxicities.
  
  
  CONCLUSIONS
  The recommended dose of topotecan for phase II studies in previously untreated patients is 6 mg/m2 on days 1, 8, and 15, every 28 days, and 4 mg/m2 appears to be a suitable dose for use in previously treated patients with this schedule.
authors.affiliation: Department of Respiratory Medicine, Kitasato University School of Medicine, Japan. masuda@med.kitasato-u.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
authors.forename: Kaoru
authors.initials: K
authors.lastname: Matsui
authors.forename: Shunichi
authors.initials: S
authors.lastname: Negoro
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.forename: Shinzoh
authors.initials: S
authors.lastname: Kudoh
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Akihira
authors.initials: A
authors.lastname: Mukaiyama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Arase
authors.forename: Pascal
authors.initials: P
authors.lastname: Yoshida
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ijima
authors.forename: Minoru
authors.initials: M
authors.lastname: Takada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016879:Salvage Therapy; D015996:Survival Rate; D014018:Tissue Distribution; D019772:Topotecan / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan