title: Phase I clinical trial of taxotere administered as either a 2-hour or 6-hour intravenous infusion.
abstract: OBJECTIVE
  To determine the potential efficacy and dose-limiting toxicity of taxotere, a hemisynthetic inhibitor of tubulin depolymerization.
  
  
  METHODS
  Fifty-eight patients were administered taxotere in this phase I clinical trial as a 6-hour or a 2-hour infusion repeated every 21 days. Forty patients received 181 courses on the 6-hour infusion schedule, and 18 patients received 105 courses on the 2-hour infusion schedule.
  
  
  RESULTS
  Neutropenia was the dose-limiting toxicity on both schedules. The maximally tolerated dose was 100 mg/m2 on the 6-hour infusion schedule and 115 mg/m2 on the 2-hour infusion schedule. The most prominent nonhematologic toxicities included mucositis (more prominent on the 6-hour infusion schedule), transient rash (more common on the 2-hour infusion schedule), and alopecia. Hypersensitivity reactions were seen in five patients. There was no evidence of neurotoxicity or cardiotoxicity. One partial response was noted on the 6-hour infusion schedule (one in refractory breast cancer) and four additional partial responses were noted on the 2-hour infusion schedule (two in adenocarcinoma of the lung, one in refractory breast cancer, one in cholangio-carcinoma). In addition, 10 patients had minor responses. Pharmacokinetic studies showed plasma concentrations of taxotere declined in a triexponential manner, with a terminal half-life of 11.8 hours.
  
  
  CONCLUSIONS
  The recommended starting dose for phase II taxotere trials is 100 mg/m2 administered as a 2-hour infusion, repeated every 21 days. Taxotere is a promising antineoplastic agent worthy of extensive phase II testing in patients with a variety of malignancies.
authors.affiliation: University of Texas Health Science Center, San Antonio.
authors.forename: H
authors.initials: H
authors.lastname: Burris
authors.forename: R
authors.initials: R
authors.lastname: Irvin
authors.forename: J
authors.initials: J
authors.lastname: Kuhn
authors.forename: S
authors.initials: S
authors.lastname: Kalter
authors.forename: L
authors.initials: L
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Shaffer
authors.forename: S
authors.initials: S
authors.lastname: Fields
authors.forename: G
authors.initials: G
authors.lastname: Weiss
authors.forename: J
authors.initials: J
authors.lastname: Eckardt
authors.forename: G
authors.initials: G
authors.lastname: Rodriguez
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D043823:Taxoids
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel