title: Paclitaxel and pegylated liposomal doxorubicin in recurrent head and neck cancer: clinical and unexpected pharmacokinetic interactions.
abstract: BACKGROUND
  The combination of paclitaxel (PTX) with pegylated liposomal doxorubicin (PLD) is an interesting treatment for recurrent head and neck cancer. The pharmacokinetic behavior may depend on the interval between the intravenous administration of the two drugs. This study evaluates the clinical efficacy, toxicity and any possible interval-dependent pharmacokinetic interactions.
  
  
  METHODS
  Thirty patients were randomized to receive 80 mg/m2 PTX weekly and 12.5 mg/m2 PLD every two weeks at administration intervals of 0, 1, 3, 12 or 24 hours. Blood sampling was performed at day 1 and 15 and pharmacokinetics of PTX, PLD and Cremophor EL were evaluated by non-compartmental analysis.
  
  
  RESULTS
  Neutropenia was the most frequent side-effect (100% of patients; 30% grade 3-4). Hand-foot syndrome was severe in only 3% of patients. Overall response rate was 30%, with 3% complete responses and 27% partial responses. Stable disease and progression were 43% and 27%, respectively. Median response duration and overall median survival were 5.5 and 10 months respectively. Co-administration of PLD markedly reduced Cmax and the area under the curve (AUC), and increased PTX clearance. The differences in the PTX AUC and clearance between the 0 h and the 24 h experimental arms were statistically significant.
  
  
  CONCLUSIONS
  The PTX/PLD combination plays a palliative role (clinical benefit in 73% of patients) and has good tolerability. The PTX pharmacokinetic profile was unexpectedly affected by different administration time intervals; in the 0 h arm the AUC was reduced to one fourth, therefore a schedule with PTX on day one, PLD on day two may be preferred.
authors.affiliation: Medical Oncology Department, San Giovanni Antica Sede Hospital, Turin, Italy. airoldim@yahoo.com
authors.forename: Mario
authors.initials: M
authors.lastname: Airoldi
authors.forename: Luigi
authors.initials: L
authors.lastname: Cattel
authors.forename: Paola
authors.initials: P
authors.lastname: Milla
authors.forename: Fulvia
authors.initials: F
authors.lastname: Pedani
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Garzaro
authors.forename: Franco
authors.initials: F
authors.lastname: Dosio