title: Phase I study of docetaxel administered as a 1-hour intravenous infusion on a weekly basis.
abstract: OBJECTIVE
  This phase I study of Taxotere (RP 56976, NSC 628503; docetaxel, Rhône-Poulenc Rorer, Antony, France) was undertaken to determine the maximum-tolerated dose (MTD), toxic effects, and basic pharmacokinetics of a day-1 and -8 schedule of this novel semisynthetic product related to Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT).
  
  
  METHODS
  Thirty-two eligible patients with refractory solid malignancies have been treated with a 1-hour infusion of Taxotere on a day-1 and -8 schedule every 3 weeks as long as patients maintained a polymorphonucleotide count > or = 1,500/microL and a platelet count > or = 100,000/microL. Dose levels tested have ranged between 20 and 110 mg/m2 per course.
  
  
  RESULTS
  Considering 128 assessable courses, the main toxicities have been neutropenia (which was dose-limiting), asthenia, alopecia, hypersensitivity reactions, skin toxicity, and edema. No significant cardiac or platelet toxicity has been observed. Seven patients have had aggravation of preexisting paresthesias or new onset of sensory symptoms during Taxotere treatment. The MTD at this schedule appears to be 110 mg/m2 per course, with six of 10 patients at this level experiencing severe toxicity. Five partial remissions have been observed in four heavily pretreated patients with breast cancer and in one patient with adenocarcinoma of unknown origin. Two patients with ovarian cancer have had meaningful decreases in CA125 levels.
  
  
  CONCLUSIONS
  Like Taxol, this novel chemotherapeutic agent appears to possess promising activity in patients with refractory breast and ovarian neoplasms, with tolerable toxicities. Using this schedule, 100 mg/m2 per course is the recommended dose for future phase II trials.
authors.affiliation: Service de Médecine et Laboratoire d'Investigation, Clinique H.J. Tagnon, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Tomiak
authors.forename: M J
authors.initials: MJ
authors.lastname: Piccart
authors.forename: J
authors.initials: J
authors.lastname: Kerger
authors.forename: S
authors.initials: S
authors.lastname: Lips
authors.forename: A
authors.initials: A
authors.lastname: Awada
authors.forename: D
authors.initials: D
authors.lastname: de Valeriola
authors.forename: C
authors.initials: C
authors.lastname: Ravoet
authors.forename: D
authors.initials: D
authors.lastname: Lossignol
authors.forename: J P
authors.initials: JP
authors.lastname: Sculier
authors.forename: V
authors.initials: V
authors.lastname: Auzannet
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D043823:Taxoids; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel