title: Randomized phase II study of two schedules of topotecan in previously treated patients with ovarian cancer: a National Cancer Institute of Canada Clinical Trials Group study.
abstract: OBJECTIVE
  As topotecan is S-phase-specific, its efficacy is likely schedule-dependent. Therefore, a randomized study using a "pick the winner" design was undertaken to compare two schedules in patients with recurrent ovarian cancer.
  
  
  METHODS
  Patients with recurrent epithelial ovarian cancer previously treated with no more than two separate regimens of chemotherapy, one of which had to be platinum-containing, were randomized to either topotecan 1.5 mg/m2 intravenously (i.v.) over 30 minutes daily for 5 days repeated every 21 days (arm A, the standard arm), or topotecan 1.75 mg/m2 as a 24-hour infusion once a week for 4 weeks repeated every 6 weeks (arm B, the experimental arm).
  
  
  RESULTS
  Sixty-six patients were eligible and 63 were assessable for response. The response rate in arm A was 22.6% (95% confidence interval [CI], 9.6% to 41.2%), which was significantly superior to that in arm B, 3.1% (95% CI, 0.1% to 16%) (P = .026). The regimens were not equitoxic, with 94% of patients on arm A experiencing grade 3 or 4 granulocytopenia as opposed to 52% on arm B.
  
  
  CONCLUSIONS
  The weekly 24 hour infusion of topotecan at 1.75 mg/m2 was ineffective in relapsed ovarian cancer. The daily-times-five schedule remains the schedule of choice. As the regimens were not equitoxic, one cannot differentiate between an ineffective schedule and an ineffective dose as the reason for the differing response rates. However, the degree of myelotoxicity that already occurs will preclude any substantially higher dosing with the weekly regimen.
authors.affiliation: National Cancer Institute of Canada Clinical Trials Group, Queen's University, Kingston, Canada. phoskins@bccancer.bc.ca
authors.forename: P
authors.initials: P
authors.lastname: Hoskins
authors.forename: E
authors.initials: E
authors.lastname: Eisenhauer
authors.forename: S
authors.initials: S
authors.lastname: Beare
authors.forename: M
authors.initials: M
authors.lastname: Roy
authors.forename: P
authors.initials: P
authors.lastname: Drouin
authors.forename: G
authors.initials: G
authors.lastname: Stuart
authors.forename: P
authors.initials: P
authors.lastname: Bryson
authors.forename: R
authors.initials: R
authors.lastname: Grimshaw
authors.forename: V
authors.initials: V
authors.lastname: Capstick
authors.forename: B
authors.initials: B
authors.lastname: Zee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D019772:Topotecan