title: Weekly docetaxel in minimally pretreated cancer patients: a dose-escalation study focused on feasibility and cumulative toxicity of long-term administration.
abstract: BACKGROUND
  Docetaxel is an agent with impressive clinical activity but a rather poor profile of toxicity when given every three weeks. Therefore, optimisation of its clinical use is highly warranted. This is a dose-escalation study of weekly docetaxel particularly focused on the feasibility of long-term administration and characterisation of cumulative toxicity.
  
  
  METHODS
  Twenty-six patients (11 female/15 male, median age 56, range 23-73) were treated over the range of 25-50 mg/m2/week. Dose-limiting toxicity for this schedule was defined as any grade > 2 antiproliferative toxic effect resulting in a > 2-week delay for re-administration of the drug, or any grade > 2 organ-specific toxicity. Patients were monitored clinically and electrophysiologically for neurotoxicity. No prolonged corticosteroid co-medication or prophylactic haematopoietic growth factors were given.
  
  
  RESULTS
  A median/mean number of 8.5/8.7 consecutive weekly courses were given per patient. The maximum tolerated dose that prevented on-schedule administration of the drug was 50 mg/m2. The main cumulative toxicities were a mild fluid retention and dacryorrhea which became evident as the number of treatment courses increased. Grade 2 alopecia and fatigue were observed only at 45 mg/m2 and higher. Activity was seen at all of the dose levels studied.
  
  
  CONCLUSIONS
  Long-term weekly administration of docetaxel is feasible at doses up to 45 mg/m2/week with acceptable toxicity. Further clinical evaluation is justified at this schedule and 40 mg/m2/week of docetaxel is proposed for phase II studies as an active dose with minimal toxicity.
authors.affiliation: Medical Oncology Department, Ioannina University Hospital, Greece. ebriasou@otenet.gr
authors.forename: E
authors.initials: E
authors.lastname: Briasoulis
authors.forename: V
authors.initials: V
authors.lastname: Karavasilis
authors.forename: D
authors.initials: D
authors.lastname: Anastasopoulos
authors.forename: E
authors.initials: E
authors.lastname: Tzamakou
authors.forename: G
authors.initials: G
authors.lastname: Fountzilas
authors.forename: D
authors.initials: D
authors.lastname: Rammou
authors.forename: V
authors.initials: V
authors.lastname: Kostadima
authors.forename: N
authors.initials: N
authors.lastname: Pavlidis
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D043823:Taxoids
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel