title: Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer.
abstract: BACKGROUND
  Paclitaxel (Taxol), a diterpene plant product that promotes tubulin polymerization, has documented activity against a number of solid tumors, including ovarian cancer and breast cancer.
  
  
  OBJECTIVE
  Our purpose was to conduct a phase II clinical trial investigating the response of patients with advanced recurrent ovarian carcinoma to high-dose paclitaxel combined with granulocyte colony-stimulating factor (G-CSF).
  
  
  METHODS
  A prospective phase II clinical trial of patients with advanced-stage, recurrent ovarian cancer was undertaken. Patients received 250 mg/m2 paclitaxel every 21 days; cycles were given on a rigid schedule; delays were permitted only for extreme circumstances. G-CSF at a dose of 10 micrograms/kg per day was given to ameliorate myelo-suppression. If a patient showed fever and neutropenia, G-CSF dosage was increased to 20 micrograms/kg per day so that paclitaxel dose intensity could be maintained. Patients were assessed for response every two cycles, and those with complete radiographic resolution of disease underwent peritoneoscopy.
  
  
  RESULTS
  Forty-four patients were assessable for response. Twenty-one had a reduction in tumor volume greater than 50%, yielding an objective response rate of 48% (21 of 44 patients; 95% confidence interval, 32%-63%). Six (14%) of the 44 patients had complete radiographic resolution of disease; two of the six also had negative biopsy specimens and washings at peritoneoscopy. Age, number of prior regimens, and clinical platinum resistance did not influence response rate or ability to maintain dose intensity. Dose intensity was maintained at the targeted level for up to 14 consecutive cycles of therapy.
  
  
  CONCLUSIONS
  We observed a 48% response rate with dose-intense paclitaxel for patients with advanced-stage, platinum-resistant, recurrent ovarian cancer. The response rate is higher than previously reported for paclitaxel at a lower dose in similar cohorts of patients treated without G-CSF. Comparison of phase II studies of paclitaxel suggests a dose-response relationship. Therapy with dose-intense paclitaxel and G-CSF should be considered for patients with advanced, platinum-refractory ovarian cancer.
authors.affiliation: Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: E C
authors.initials: EC
authors.lastname: Kohn
authors.forename: G
authors.initials: G
authors.lastname: Sarosy
authors.forename: A
authors.initials: A
authors.lastname: Bicher
authors.forename: C
authors.initials: C
authors.lastname: Link
authors.forename: M
authors.initials: M
authors.lastname: Christian
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: M
authors.initials: M
authors.lastname: Rothenberg
authors.forename: D O
authors.initials: DO
authors.lastname: Adamo
authors.forename: P
authors.initials: P
authors.lastname: Davis
authors.forename: F P
authors.initials: FP
authors.lastname: Ognibene
mesh_terms: D000328:Adult; D000368:Aged; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D002277:Carcinoma / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017671:Platinum Compounds / Q000627:therapeutic use; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D017671:Platinum Compounds; D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel