title: Randomized phase II study of two irinotecan schedules for patients with metastatic breast cancer refractory to an anthracycline, a taxane, or both.
abstract: OBJECTIVE
  A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules.
  
  
  METHODS
  MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m(2) weekly for 4 weeks, then a 2-week rest (weekly) or 240 mg/m(2) every 3 weeks.
  
  
  RESULTS
  The weekly arm had 52 assessable patients; the every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective response (complete regression [CR] + partial regression [PR]) rate was 23% (one CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range, 1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to 14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to 13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3 months). Treatment generally was well tolerated, especially in the weekly arm. Grade 3 to 4 adverse events with > or = 10% incidence included neutropenia (29%) and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%), dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm.
  
  
  CONCLUSIONS
  Irinotecan is active with good tolerability in refractory MBC. Irinotecan (especially weekly) warrants additional study as monotherapy and in combination regimens in this setting.
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA. perez.edith@mayo.edu
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: David W
authors.initials: DW
authors.lastname: Hillman
authors.forename: James A
authors.initials: JA
authors.lastname: Mailliard
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: J Michael
authors.initials: JM
authors.lastname: Ryan
authors.forename: Tom R
authors.initials: TR
authors.lastname: Fitch
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
authors.forename: Carl G
authors.initials: CG
authors.lastname: Kardinal
authors.forename: James E
authors.initials: JE
authors.lastname: Krook
authors.forename: John W
authors.initials: JW
authors.lastname: Kugler
authors.forename: Shaker R
authors.initials: SR
authors.lastname: Dakhil
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077146:Irinotecan; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011446:Prospective Studies; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D043823:Taxoids; D000077146:Irinotecan; D002166:Camptothecin