title: Single-agent topotecan as first-line chemotherapy in women with metastatic breast cancer: final results of eastern cooperative oncology group trial E8193.
abstract: OBJECTIVE
  The purpose of this multicenter phase II trial was to evaluate the clinical activity of topotecan as first-line chemotherapy in patients with metastatic breast cancer and previous exposure to adjuvant doxorubicin.
  
  
  METHODS
  Patients with measurable disease received a 72-hour continuous intravenous infusion of topotecan 1.3 mg/m(2) per day repeated every 21 days. The primary objective was to determine whether > or = 4 responses were observed among 30 evaluable patients after 3 cycles of therapy using a 2-stage design (> or = 2 responses required in the first 20 evaluable patients). Duration of response, time to tumor progression, overall survival, and toxicity were also examined. Thirty-five patients altogether received 78 cycles of therapy (median, 3 cycles; range, 1-8 cycles).
  
  
  RESULTS
  Two partial responses (6%; 95% confidence interval, 0.7%-19%) were observed among 30 evaluable patients (median age, 55 years; range, 34-76 years; median Eastern Cooperative Oncology Group performance status, 0; range, 0-2). Median time to progression and overall survival were 2.3 months and 18.7 months, respectively. Myelosuppression was the most common toxicity among 34 evaluable patients (grade 3/4 neutropenia and thrombocytopenia in 62% and 53%, respectively) with only 1 life-threatening event.
  
  
  CONCLUSIONS
  Although tolerable, this dose and schedule of topotecan has limited activity in unselected patients with breast cancer even as first-line therapy. Identification of potential predictive markers of response and toxicity is encouraged before considering further studies of topotecan and camptothecin analogues in breast cancer.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA. awolff@jhmi.edu
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.forename: Anne
authors.initials: A
authors.lastname: O'Neill
authors.forename: M John
authors.initials: MJ
authors.lastname: Kennedy
authors.forename: James A
authors.initials: JA
authors.lastname: Stewart
authors.forename: William J
authors.initials: WJ
authors.lastname: Gradishar
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Lord
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: William C
authors.initials: WC
authors.lastname: Wood
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary*; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004264:DNA Topoisomerases, Type I / Q000187:drug effects; D004317:Doxorubicin / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D012983:Soft Tissue Neoplasms / Q000556:secondary; D019772:Topotecan / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D019772:Topotecan; D004317:Doxorubicin; D004264:DNA Topoisomerases, Type I