title: Phase II study of topotecan in patients with recurrent malignant glioma. National Clinical Institute of Canada Clinical Trials Group.
abstract: BACKGROUND
  The NCIC Clinical Trial Group has an ongoing interest in assessing investigational agents in minimally pretreated patients with malignant glioma. Topotecan is one of the first topoisomerase I inhibitors to enter clinical trials and has shown early evidence of activity in several solid tumors. We have conducted a phase II trial of topotecan in patients with malignant glioma.
  
  
  METHODS
  Adults with malignant glioma and recurrent contrast enhancing measurable disease (> or = 2 x 2 cm) were eligible. Topotecan 1.5 mg/m2 i.v. was given daily x five days every three weeks. Response and toxic effects were assessed at the end of each cycle.
  
  
  RESULTS
  Thirty-one patients were entered onto the study: fifteen had glioblastoma, 16 anaplastic astrocytoma, all had prior radiation, 15 prior chemotherapy, and all were assessable for response and toxicity. Two patients (6%) responded: one had a complete radiographic response, but died with neutropenic sepsis, and the second had a prolonged partial response (> 97 weeks). Twenty-one patients (68%) had stable disease for five to 86 + weeks (median 19) and eight (26%) had progressive disease after one cycle. Toxicity was primarily hematologic; 18 (58%) had grade 4 neutropenia (< 0.5 x 10(9)/1), usually brief, and three (10%) grade 4 thrombocytopenia (< 25 x 10(9)/1). Twelve of 109 cycles (11%) were given at reduced dose.
  
  
  CONCLUSIONS
  Topotecan in this dose and schedule has only modest activity in recurrent glioblastoma and anaplastic astrocytoma.
authors.affiliation: Department of Clinical Neurological Sciences, University of Western Ontario, London, Kingston, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Macdonald
authors.forename: G
authors.initials: G
authors.lastname: Cairncross
authors.forename: D
authors.initials: D
authors.lastname: Stewart
authors.forename: P
authors.initials: P
authors.lastname: Forsyth
authors.forename: C
authors.initials: C
authors.lastname: Sawka
authors.forename: N
authors.initials: N
authors.lastname: Wainman
authors.forename: E
authors.initials: E
authors.lastname: Eisenhauer
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D019772:Topotecan; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan; D002166:Camptothecin