Clinical pharmacokinetics of low dose paclitaxel in Asian patients with nasopharyngeal carcinoma

Abstract

The pharmacokinetics (PK) of low-dose paclitaxel in Asian patients with WHO Stage III nasopharyngeal carcinoma treated with a chemo-radiation regimen were determined and correlated with subjecta??s demographics, clinical parameters, outcome with the intent of optimizing therapeutic benefit to risk ratio in clinical use. Chemotherapy, consisting of hydroxyurea, paclitaxel and 5-flourouracil were given concurrently with radiotherapy during the first, fourth and seventh week of the treatment. Plasma paclitaxel concentrations were determined by a validated HPLC method and the sparse data were used to generate a population PK model. The model predicted the plasma concentration well although there was an outlier. The PK parameters derived using KineticaA? population two-compartment i.v. infusion model were consistent with published data. The elimination rate constant of the model was related to height and pre- and post- therapy total white blood count. Hematological and non-hematological adverse effects which were reflective of this multi-agent regimen were also reported.