title: Phase I and pharmacokinetic study of escalating dose of docetaxel administered with granulocyte colony-stimulating factor support in adult advanced solid tumors.
abstract: OBJECTIVE
  The purpose of our study was to assess the feasibility, toxicity, and pharmacokinetics of an escalating dose of docetaxel when administered with granulocyte colony-stimulating factor (G-CSF) support every 3 weeks.
  
  
  METHODS
  Patients with advanced solid malignancies were treated with escalating doses of docetaxel as a 1-h infusion every 3 weeks, supported by s.c. administration of human recombinant glycosilated G-CSF Granocyte (lenograstim), 5 microg/kg/day (from day 4 until neutrophil count >0.5-10(g)/liter for two consecutive days). Plasma sampling was performed to characterize the pharmacokinetics of docetaxel at the new recommended high-dose level.
  
  
  RESULTS
  Forty-seven patients were treated with 116 courses of docetaxel at eight dose levels ranging from 100-185 mg/m(2). Dose-limiting toxicities were nonhematologic and included mucositis and dermatitis. Severe skin toxicity observed at 185 mg/m(2) led to discontinuing the study, and 175 mg/m(2) was selected as the recommended dose of docetaxel + G-CSF for future Phase II studies. Analysis of multiple courses revealed dermatitis, mucositis, arthralgia/myalgia, and neuropathy as the main dose-related toxic events. At 175 mg/m(2) mean +/- SD values for docetaxel plasmatic peak, area under the curve, clearance, volume of distribution, and terminal half-life were 6.7 +/- 1.7 microg/ml, 9.7 +/- 4 microg.h/ml, 34.2 +/- 12 liters/h, and 122.7 +/- 124 liters, respectively. Of the 16 patients treated at 175 mg/m(2), 8 patients responded (7 breast cancer and 1 lung cancer patients) including one complete response (1 breast cancer patient).
  
  
  CONCLUSIONS
  Using G-CSF support allows substantial dose escalation of docetaxel. Whether such a dose increase improves the response rate warrants further investigation. At the highest dose level studied, pharmacokinetic parameters seem to maintain a linear profile.
authors.affiliation: Department of Medicine, Institut Paoli-Calmettes, 13273 Marseille, France. oncomed@marseille.fnclcc.fr
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalves
authors.forename: Frederic
authors.initials: F
authors.lastname: Viret
authors.forename: Joseph
authors.initials: J
authors.lastname: Ciccolini
authors.forename: Dominique
authors.initials: D
authors.lastname: Genre
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Gravis
authors.forename: Marc
authors.initials: M
authors.lastname: Giovanini
authors.forename: Jacques
authors.initials: J
authors.lastname: Camerlo
authors.forename: Jacques
authors.initials: J
authors.lastname: Catalin
authors.forename: Dominique
authors.initials: D
authors.lastname: Maraninchi
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology; D001943:Breast Neoplasms / Q000628:therapy; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000493:pharmacokinetics*; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D043823:Taxoids; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D017239:Paclitaxel