Pharmacokinetics and Pharmacogenetics-based Adaptive Dosing of 5-fu (5-Fluorouracile) in Head & Neck Cancer Patient Undergoing Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) Therapy
Condition: Patients With Head and Neck Cancer (ORL)
MeSH terms: Head and Neck Neoplasms
Study type: Interventional
Phase: Phase 4

Summary: 
      Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) is a mainstay for treating head and neck
      cancers, but elderly or fragile patients are often precluded because of the risk of severe
      toxicities associated with this protocol. DPD (Dihydro Pyrimidine Dehydrogenase) deficiency
      is a pharmacogenetic syndrome responsible for most of the severe/lethal toxicities showing in
      5-FU (5-Fluorouracile)-treated patients, and our institute has developed a strategy for the
      routine determination of Dihydro Pyrimidine Dehydrogenase (DPD) status prior to starting
      giving the 5-FU so as to roughly adapt drug dosage according to the Dihydro Pyrimidine
      Dehydrogenase (DPD) status. This project aims at developing a Bayesian strategy to further
      individualize 5-FU dosing to reach a target exposure of area under curve (AUC). To this end,
      100 patients with head and neck cancer and scheduled for a Docetaxel, Cisplatin,
      5-Fluorouracile (=TPF) regimen will be included.
    

Detailed description: 
      Crop the plasma exposure of 5-FU (5-Fluorouracile) around a predefined target area under the
      curve 30 (AUC30) in patients with head and neck cancer treated with Docetaxel, Cisplatin,
      5-Fluorouracile (=TPF) protocols and correlate adaptive Bayesian procedure to tolerability.

        -  Develop a population die from a group of 20 patients for which a pharmacokinetic study
           will be carried out

        -  Evaluate obtaining effective concentration of 5-FU in the context of a Docetaxel,
           Cisplatin, 5-Fluorouracile (=TPF) protocol adapted by the Bayesian procedure.

        -  Compare recommendations in terms of dosage adjustment of Bayesian approach with the
           recommendations of a simplified graphical approach.

        -  Test the measure of Dihydro Pyrimidine Dehydrogenase (DPD) activity
           Dihydrouracil/Uracile (UH2 / U ratio) as a co-variable adjustment of 5-Fluorouracile
           (5-FU) regimens in Pharmacogenomics/Pharmacokinetic (PGx / PK) model.

        -  Evaluate a prototype of urinary dipsticks for the early detection of toxicity from the
           assay as a marker of Dihydro Pyrimidine Dehydrogenase (DPD) activity.

        -  Assess the cost-benefit of dosage targeting, in terms of reduction resulting costs to
           the management of chemotherapy-induced toxicities.
    

Intervention name(s): Cisplatin; Docetaxel; 5-Fluorouracile
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Antineoplastic cytostatic. Blood sampling for pharmacokinetic evaluation; Taxanes. Blood sampling for pharmacokinetic evaluation; Antineoplastic and immunomodulating agents. Blood sampling for pharmacokinetic evaluation
Intervention MeSH terms: Docetaxel
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment