title: Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group.
abstract: OBJECTIVE
  Liposomal lurtotecan (OSI-211) is a liposomal formulation of the water-soluble topoisomerase I inhibitor lurtotecan (GI147211), which demonstrated superior levels of activity compared with topotecan in preclinical models. We studied two schedules of OSI-211 in a randomized design in relapsed ovarian cancer to identify the more promising of the two schedules for further study.
  
  
  METHODS
  Eligible patients had measurable epithelial ovarian, fallopian, or primary peritoneal cancer that was recurrent after one or two prior regimens of chemotherapy. Patients were randomly assigned to receive either arm A (OSI-211 1.8 mg/m(2)/d administered by 30-minute intravenous infusion on days 1, 2, and 3 every 3 weeks) or arm B (OSI-211 2.4 mg/m(2)/d administered by 30-minute intravenous infusion on days 1 and 8 every 3 weeks). The primary outcome measure was objective response, which was confirmed by independent radiologic review, and a pick the winner statistical design was used to identify the schedule most likely to be superior.
  
  
  RESULTS
  Eighty-one patients were randomized between October 2000 and September 2001. The hematologic toxic effects were greater on arm A than on arm B (grade 4 neutropenia, 51% v 22%, respectively), as was febrile neutropenia (26% v 2.4%, respectively). Of the 80 eligible patients, eight patients (10%) had objective responses; six responders (15.4%; 95% CI, 6% to 30%) were in arm A and two responders (4.9%; 95% CI, 1% to 17%) were in arm B.
  
  
  CONCLUSIONS
  The OSI-211 daily for 3 days intravenous schedule met the statistical criteria to be declared the winner in terms of objective response. This schedule was also associated with more myelosuppression than the schedule of OSI-211 administered in arm B.
authors.affiliation: MBBS, MRCP, ILTM, Department of Medical Oncology, University of Newcastle, Westgate Rd, Newcastle upon Tyne, NE4 6BE, United Kingdom. graham.dark@ncl.ac.uk
authors.forename: Graham G
authors.initials: GG
authors.lastname: Dark
authors.forename: A Hilary
authors.initials: AH
authors.lastname: Calvert
authors.forename: Robert
authors.initials: R
authors.lastname: Grimshaw
authors.forename: Christopher
authors.initials: C
authors.lastname: Poole
authors.forename: Ken
authors.initials: K
authors.lastname: Swenerton
authors.forename: Stan
authors.initials: S
authors.lastname: Kaye
authors.forename: Robert
authors.initials: R
authors.lastname: Coleman
authors.forename: Gordon
authors.initials: G
authors.lastname: Jayson
authors.forename: Tien
authors.initials: T
authors.lastname: Le
authors.forename: Susan
authors.initials: S
authors.lastname: Ellard
authors.forename: Marc
authors.initials: M
authors.lastname: Trudeau
authors.forename: Paul
authors.initials: P
authors.lastname: Vasey
authors.forename: Marta
authors.initials: M
authors.lastname: Hamilton
authors.forename: Terri
authors.initials: T
authors.lastname: Cameron
authors.forename: Emma
authors.initials: E
authors.lastname: Barrett
authors.forename: Wendy
authors.initials: W
authors.lastname: Walsh
authors.forename: Lynn
authors.initials: L
authors.lastname: McIntosh
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Eisenhauer
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002170:Canada; D004334:Drug Administration Schedule; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; C091719:lurtotecan; D002166:Camptothecin