In:
Therapeutic Drug Monitoring, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. 5 ( 2016-10), p. 567-572
Abstract:
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 2 followed by weekly infusions of 250 mg/m 2 . 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 V 1 = 3.18 L (6%), peripheral volume of distribution V 2 = 5.4 L (42%), elimination clearance CL = 0.57 L/d (31%), distribution clearance Q = 0.64 L/d, and zero-order elimination rate k 0 = 6.72 mg/d (29%). Both V 1 and V 2 increased with the body surface area. Adjunction of chemotherapy reduced CL and increased k 0 . 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.
Type of Medium:
Online Resource
ISSN:
0163-4356
DOI:
10.1097/FTD.0000000000000321
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2016
detail.hit.zdb_id:
2048919-5
SSG:
15,3
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