Cetuximab Pharmacokinetics Influences Overall Survival in Patients With Head and Neck Cancer.
Ther Drug Monit
; 38(5): 567-72, 2016 10.
Article
en En
| MEDLINE
| ID: mdl-27631463
ABSTRACT
BACKGROUND:
A retrospective study was conducted to analyze interindividual variability of cetuximab pharmacokinetics and its influence on survival (progression-free survival and overall survival [OS]) in a cohort of head and neck squamous cell carcinoma (HNSCC).METHODS:
Thirty-four patients received cetuximab as an infusion loading dose of 400 mg/m followed by weekly infusions of 250 mg/m. Twenty-one patients had locally advanced HNSCC, and 13 had metastatic/recurrent HNSCC. Cetuximab concentrations were measured by the enzyme-linked immunosorbent assay, and its pharmacokinetics was analyzed by a population approach. Survivals were analyzed with the log-rank test.RESULTS:
Cetuximab pharmacokinetics was best described using a 2-compartment model with both first-order and saturable (zero-order) eliminations. Estimated pharmacokinetic parameters (%CV) were central volume of distribution V1 = 3.18 L (6%), peripheral volume of distribution V2 = 5.4 L (42%), elimination clearance CL = 0.57 L/d (31%), distribution clearance Q = 0.64 L/d, and zero-order elimination rate k0 = 6.72 mg/d (29%). Both V1 and V2 increased with the body surface area. Adjunction of chemotherapy reduced CL and increased k0. OS was inversely related with cetuximab global clearance (P = 0.007) and was higher in patients with severe radiation dermatitis (P = 0.005).CONCLUSIONS:
Cetuximab pharmacokinetics in patients with HNSCC can be described using a 2-compartment model combining linear and nonlinear mechanisms of elimination. OS is associated with both cetuximab global clearance and severe radiation dermatitis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Escamosas
/
Anticuerpos Monoclonales Humanizados
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Cetuximab
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Neoplasias de Cabeza y Cuello
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Ther Drug Monit
Año:
2016
Tipo del documento:
Article
País de afiliación:
Francia