title: Phase II study of exatecan mesylate (DX-8951f) as first line therapy for advanced non-small cell lung cancer.
abstract: BACKGROUND
  Exatecan mesylate (DX-8951f) is a water soluble analogue of camptothecin that inhibits topoisomerase I. This multi-centre phase II study evaluated the activity of single agent exatecan in previously untreated patients with advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with histologically or cytologically proven stage IIIb or IV NSCLC were treated with exatecan 0.5 mg/m(2) per day by 30 min intra-venous (i.v.) infusion for 5 days every 3 weeks to a maximum of six cycles. Measurable disease was documented prior to study entry and patients were re-staged every two cycles. Pharmacokinetic (PK) sampling was performed during cycle one.
  
  
  RESULTS
  39 patients (32 patients ECOG performance status 0 or 1; 29 male and ten female; mean age 63 years) were entered into the study. Thirty-three completed at least two cycles of exatecan and 11 completed six cycles. Two patients (5.1%, 95% C.I. 0.3-21.3%) had a partial response, 7 (18.0%) minor response and 8 (20.5%) stable disease. Median time to tumour progression (TTP) was 88 days and median overall survival 262 days. The main toxicity was reversible neutropenia. PK analysis of exatecan demonstrated a mean clearance of 2.28 l/h per m(2), volume of distribution 18.2 l/m(2) and mean elimination half-life of 7.9 h.
  
  
  CONCLUSIONS
  Exatecan mesylate has limited activity in advanced NSCLC and is not recommended for further evaluation as a single agent in this tumour type. PK data from this trial supports results established in phase I studies.
authors.affiliation: Cancer Research UK Medical Oncology Unit, Churchill Hospital, Oxford OX3 7LJ, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Braybrooke
authors.forename: M
authors.initials: M
authors.lastname: Ranson
authors.forename: C
authors.initials: C
authors.lastname: Manegold
authors.forename: K
authors.initials: K
authors.lastname: Mattson
authors.forename: N
authors.initials: N
authors.lastname: Thatcher
authors.forename: P
authors.initials: P
authors.lastname: Cheverton
authors.forename: M
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: R
authors.initials: R
authors.lastname: Oyama
authors.forename: D C
authors.initials: DC
authors.lastname: Talbot
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D004334:Drug Administration Schedule; D005260:Female; D005387:Finland; D005858:Germany; D006801:Humans; D007262:Infusions, Intravenous; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016019:Survival Analysis; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C095887:exatecan; D002166:Camptothecin