title: Pilot study to assess toxicity and pharmacokinetics of docetaxel in patients with metastatic breast cancer and impaired liver function secondary to hepatic metastases.
abstract: BACKGROUND
  Limited clinical data are available regarding the safety of docetaxel in metastatic breast cancer patients with liver dysfunction.
  
  
  METHODS
  Eligible patients had breast cancer with impaired liver function secondary to hepatic metastases and were candidates for docetaxel therapy. They were assigned to one of five groups on the basis of total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. All other causes of liver dysfunction were excluded, and bile duct obstruction was corrected, if possible, prior to study entry. Patients received docetaxel every three weeks. The chemotherapy dose was chosen on the basis of the patient's level of hepatic dysfunction and escalated as tolerated. The primary outcome of this study was safety. The secondary outcomes were pharmacokinetic data and efficacy in terms of time to disease progression.
  
  
  RESULTS
  Twenty-three patients were enrolled. No unexpected toxicities occurred. Grade 3/4 fatigue (65%), neutropenia (30%), myalgias (26%), neutropenic fever (26%), vomiting (9%), and rash (9%) were the most common serious adverse events. The median time to progression was three months (range 1-18 months). Pharmacokinetic results indicated that patients with more severe hepatic dysfunction may have been underdosed based on our conservative dosing strategy.
  
  
  CONCLUSIONS
  Docetaxel can be administered to patients with metastatic breast cancer and liver dysfunction after dose attenuation. However, because of a narrow therapeutic index in this clinical setting, therapy should be closely monitored with subsequent dose escalation when possible.
authors.affiliation: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Eckmann
authors.forename: Laura B
authors.initials: LB
authors.lastname: Michaud
authors.forename: Edgardo
authors.initials: E
authors.lastname: Rivera
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Madden
authors.forename: Laura
authors.initials: L
authors.lastname: Esparza-Guerra
authors.forename: Jitesh
authors.initials: J
authors.lastname: Kawedia
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Booser
authors.forename: Marjorie C
authors.initials: MC
authors.lastname: Green
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D043823:Taxoids / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D043823:Taxoids; D000077143:Docetaxel
keywords: Docetaxel; chemotherapy; hepatic dysfunction; liver impairment; metastatic breast cancer; taxanes