title: A phase II study of 9-nitro-camptothecin in patients with previously treated metastatic breast cancer.
abstract: OBJECTIVE
  This Phase II study was conducted to determine the efficacy and toxicity of 9-nitro-camptothecin (9-NC) in patients with previously treated metastatic breast cancer. Pharmacokinetic samples were obtained to investigate the correlation of plasma 9-NC exposure with clinical response and toxicity.
  
  
  METHODS
  Eligible patients had histologically confirmed metastatic breast cancer with measurable or evaluable disease. Patients must have received one or two prior chemotherapy regimens for metastatic disease. 9-NC was given orally, 1.5 mg/m(2)/day for 5 days each week; response was assessed every 8 weeks. Pharmacokinetic samples were obtained on day 1 of weeks 1 and 5.
  
  
  RESULTS
  Eighteen patients were enrolled between September 1999 and May 2000; seventeen patients were evaluable for response. The most common toxicities were nausea, vomiting, urinary symptoms, fatigue and diarrhea. No objective responses were observed; six patients had stable disease. 9-NC apparent clearance ranged from 0.57 to 55.08 L/h (median 5.91 L/h); 9-NC area under the curve ranged from 38 to 2130 ng/ml x h (median 377 ng/ml x h). There was no relationship between pharmacokinetic parameters and individual patient toxicity.
  
  
  CONCLUSIONS
  9-NC has limited activity in patients with previously treated metastatic breast cancer. Though 9-NC has substantial pharmacokinetic variability in this patient population; no correlation was found between pharmacokinetic variables and toxicity.
authors.affiliation: Division of Hematology and Oncology, Indiana University, Indianapolis, Indiana 46202, USA. kathmill@iupui.edu
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Miller
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Soule
authors.forename: LaTrice G
authors.initials: LG
authors.lastname: Haney
authors.forename: Patricia
authors.initials: P
authors.lastname: Guiney
authors.forename: Darryl J
authors.initials: DJ
authors.lastname: Murry
authors.forename: Luigi
authors.initials: L
authors.lastname: Lenaz
authors.forename: Show-Li
authors.initials: SL
authors.lastname: Sun
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: D000970:Antineoplastic Agents; C079905:rubitecan; D002166:Camptothecin