ENT Medical News about head and neck squamous cell carcinoma;erlotinib

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Population pharmacokinetics of erlotinib and its pharmacokinetic/pharmacodynamic relationships in head and neck squamous cell carcinoma
European Journal of Cancer, 06/15/09

Thomas F et al. - Study concludes that erlotinib treatment may present criteria justifying dose individualisation but further studies, including more patients, are necessary to define the modalities of this adaptation.

Methods

Study was undertaken to:
- Analyse the impact of several covariates on the pharmacokinetics of erlotinib and its main metabolite (OSI-420) and
- Determine pharmacokinetic/pharmacodynamic (PK/PD) relationships
Plasma concns of erlotinib and OSI-420 of 42 pts were analysed to evaluate the impact of pts’ covariates on erlotinib PK
Presence of SNP in ABCB1 (2677G > T/A and 3435C > T), ABCG2 (421C > A) and CYP3A5 (6986G > A) was investigated
PK/PD relationships between plasma drug exposure (AUC) and early drug response or toxicity were also studied

Results

Covariates retained to predict erlotinib clearance were ALAT (alanine amino transferase), age and ABCG2 polymorphism
A significant link between drug exposure and the grade of skin rash was observed
However, early response to treatment was not correlated to the erlotinib AUC

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