title: Phase II trial of paclitaxel and topotecan with granulocyte colony-stimulating factor support in stage IV breast cancer.
abstract: OBJECTIVE
  This multicenter phase II trial investigated the efficacy and safety of a combination of paclitaxel and topotecan in patients with pretreated metastatic breast cancer. Plasma levels of paclitaxel and topotecan were obtained during cycle 1 to correlate pharmacokinetic parameters with toxicity.
  
  
  METHODS
  Paclitaxel was administered intravenously (i.v.) at 230 mg/m2 over 3 hours on day 1 followed by topotecan 1.0 mg/m2 i.v. over 30 minutes on days 1 to 5. Patients received an abbreviated premedication regimen that consisted of ranitidine 50 mg, diphenhydramine 50 mg, and a single 20-mg dose of dexamethasone, all administered i.v. 30 minutes before paclitaxel. Granulocyte colony-stimulating factor (GCSF) was administered at 5 micrograms/kg/d subcutaneously starting on day 6 and continuing until the absolute granulocyte count (AGC) was greater than 10,000/microL. Plasma paclitaxel and topotecan concentrations were assessed during the first cycle using limited-sampling strategies.
  
  
  RESULTS
  Seventeen patients were treated. The majority had visceral metastases. Four patients experienced neutropenic fever and one had mild bronchospasm. Only one partial response (PR) was observed. Nadir AGC correlated strongly with both duration of paclitaxel levels greater than 0.05 mumol/L and maximum concentration (Cmax) of paclitaxel.
  
  
  CONCLUSIONS
  This regimen does not produce a response rate superior to that expected with single-agent paclitaxel at doses that do not require growth factor support.
authors.affiliation: Section of Hematology/Oncology, University of Chicago, The University of Chicago Phase II Cooperative Network, Chicago, IL 60637-1470, USA. gfflemin@mcis.bsd.uchicago.edu
authors.forename: G F
authors.initials: GF
authors.lastname: Fleming
authors.forename: J W
authors.initials: JW
authors.lastname: Kugler
authors.forename: P C
authors.initials: PC
authors.lastname: Hoffman
authors.forename: R
authors.initials: R
authors.lastname: Ansari
authors.forename: J D
authors.initials: JD
authors.lastname: Bitran
authors.forename: A
authors.initials: A
authors.lastname: Klepsch
authors.forename: D
authors.initials: D
authors.lastname: Malone
authors.forename: A A
authors.initials: AA
authors.lastname: Fasanmade
authors.forename: M J
authors.initials: MJ
authors.lastname: Ratain
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D012044:Regression Analysis; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D019772:Topotecan; D017239:Paclitaxel