Introduction to the Clinical Pharmacokinetics of Cetuximab

PK data for cetuximab were derived from 19 clinical studies performed up to 2003 [16]. Ten of these studies were conducted as dose-escalation/dose-finding studies, while the remaining nine were conducted at the approved dosing regimen of 400 mg/m2 initially, followed by weekly doses of 250 mg/m2. 

The PK of cetuximab were investigated after single IV doses ranging from 5 to 500 mg/m2. PK data obtained after administration of cetuximab monotherapy were available from 82 patients in five of the dose-escalation studies, and from 214 patients in four of the studies with the approved dosing regimen. In two studies, cetuximab was administered both as a monotherapy and in combination with irinotecan single- as well as multiple-dose cetuximab concentration data were available from 300 patients in these two studies. 

In 10 studies the corresponding clinical study protocol stipulated that cetuximab was to be given in combination with a chemotherapeutic agent (irinotecan, paclitaxel, gemcitabine, cisplatin, carboplatin, or doxorubicin) or in combination with radiation therapy. 

In the dose-escalation studies, PK data were obtained for patients with a variety of EGFR-expressing solid cancers, while the studies at the approved dosing regimen were conducted in the indications of colorectal carcinoma, squamous cell cancer of the head-and-neck, pancreatic cancer, and renal cell cancer. 

Cetuximab serum concentrations were measured using validated enzyme-linked immunosorbent assay (ELISA) methods or a validated surface plasmon resonance assay. These bioanalytical assays were crossvalidated to allow pooling of PK data across studies. 

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