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Cetuximab pharmacokinetics

Cetuximab is a human/mouse antibody that binds to the epidermal growth factor receptor to block its stimulation. The pharmacokinetics of cetuximab demonstrate a volume of distribution that approximates the vascular space and a terminal half-life of 70 to 100 hours. Cetuximab has shown clinical activity in the treatment of colorectal cancer. An acnelike rash may appear on the face and upper torso 1 to 3 weeks after the start of therapy. Other side effects include hypersensitivity reactions, interstitial lung disease, fever, malaise, diarrhea, abdominal pain, and nausea and vomiting. [Pg.1294]

Whether administered in combination or as a single therapy for cancers of the head, neck and colon, cetuximab exhibits similar pharmacokinetic characteristics. After a 2-h infusion of 400 mg/m2, the half-life is 97 h, ranging from 41 to 213 h, and after initial and subsequent maintenance doses, the half-life is about 112 h, ranging from 63 to 230 h. The adverse effects associated with cetuximab include immuno-genicity, electrolyte depletion (hypomagnesemia) and infusion reactions. Infusion reactions involve airway obstruction, urticaria and hypotension. [Pg.121]

Bevacizumab, a humanized IgG and cetuximab, a chimeric IgGx, are currently marketed in the US for treatment of metastatic colorectal cancer [92, 93]. Bevacizumab neutralizes the biological activity of vascular endothelial growth factor (VEGF), while cetuximab binds specifically to the extracellular domain of the human epidermal growth factor receptor (EGFR). Bevacizumab, in combination with IV 5-fluorouracil (5-FU) -based chemotherapy, is indicated for first-line treatment of metastatic colorectal cancer, whereas cetuximab is used in patients refractory to or intolerant to irinotecan-based chemotherapy. The clinical pharmacokinetics of cetuximab are discussed in detail in Chapter 14. [Pg.318]

Early clinical studies are performed in cancer patients in hospitals instead of healthy volunteers, and in specialized Phase I units. Selection criteria for patients entered into cetuximab Phase I studies included various important factors such as disease state, life expectancy (>3 months), prior treatment, organ function, age, tumor type and target (i.e., EGFR expression). Therefore, pharmacokinetic (PK) data obtained from these individuals is confounded by numerous factors, a fact usually absent in conventional studies with tightly controlled, well-selected healthy subjects performed for non-oncologic drags. [Pg.354]

Table 14.1 Single-dose pharmacokinetic parameters for cetuximab across all studies. [Pg.358]

Table 14.3 Main pharmacokinetic parameters for cetuximab during week 4 of dosing. ... Table 14.3 Main pharmacokinetic parameters for cetuximab during week 4 of dosing. ...
The selection of the appropriate population pharmacokinetic base model was guided by the following criteria a significant reduction in the objective function value (p < 0.01,6.64 points) as assessed by the Likelihood Ratio Test the Akaike Information Criterion (AIC) a decrease in the residual error a decrease in the standard error of the model parameters randomness of the distribution of individual weighted residuals versus the predicted concentration and versus time post start of cetuximab administration randomness of the distribution of the observed concentration versus individual predicted concentration values around the line of identity in a respective plot. [Pg.364]

Table 14.4 Cetuximab population pharmacokinetic analysis final model parameter estimates. Table 14.4 Cetuximab population pharmacokinetic analysis final model parameter estimates.
Fig. 14.6 Simulation of clearance (CL) for cetuximab versus concentration, based on the results of the integrated population pharmacokinetic analysis. Fig. 14.6 Simulation of clearance (CL) for cetuximab versus concentration, based on the results of the integrated population pharmacokinetic analysis.
Table 14.5 Pharmacokinetic parameters of irinotecan before and after cetuximab co-administration. Table 14.5 Pharmacokinetic parameters of irinotecan before and after cetuximab co-administration.
Table 14.6 Pharmacokinetic parameters of cetuximab before and after irinotecan co-administration. Table 14.6 Pharmacokinetic parameters of cetuximab before and after irinotecan co-administration.
C. Farrell, H. Pentikis, A. Nolting, M. Birk-hofer, and M. Needle. 2004. A population pharmacokinetic (PPK) analysis of the anti-EGFR specific IgGl monoclonal antibody cetuximab. Poster at the Annual ASCO Gastrointestinal Cancers Symposium, January 22-24, A290. [Pg.370]

A. Kovar, and E. Raymond. 2005. Pharmacokinetic profile of cetuximab (Erbitux ) alone and in combination with irinotecan in patients with advanced EGFR-positive adenocarcinoma. Eur. J. Cancer 41 1739-1745. [Pg.371]

The issue of inadequate sampling time is exemplified by monoclonal antibodies. As shown in Table 32.12/ the Vi and Vss are similar and are similar in size to a vascular space of 2-3 L/m. It is also important to note that for the most part/ in the studies submitted to support New Drug Application (NDA) approval/ Vgs was determined with methods assuming linear/ first-order kineticS/ and clearly this is not the case for the majority of the monoclonal antibodies currently marketed/ such as cetuximab (Erbitux). In fact/ the use of noncompartmental methods to describe the pharmacokinetics of mABs oversimplifies their complex properties. [Pg.487]

Given the complexities of the pharmacology and pharmacokinetics of therapeutic proteins, the effect of race would not be expected to be important. There is no known difference between racial characteristics that would cause additional PK variability. Attempts have been made to examine the effect of race as a covariate, but it has only rarely been identified once patient weight or sex and other covariates (particularly those related to disease) were taken into account. Such was the case for cetuximab (70). [Pg.1010]

Cetuximab displays nonlinear pharmacokinetics. Following the recommended dose regimen, steady-state levels are achieved by the third weekly infusion. The mean t is 114 hours (range, 75—188 hours). Toxic side effects observed with cetuximab include infusion reactions. The incidence of rash is significantly greater than that observed with other monoclonal antibodies it may occur in 75% of patients, and may be severe in 16%. Interestingly, there is a correlation between development and intensity of rash and duration of benefit from cetuximab. [Pg.904]

No pharmacokinetic interaction occurs between cetuximab and irinotecan. [Pg.619]

Cetuximab is used with irinotecan in the treatment of metastatie eoloreetal eaneer. In a study 14 patients with advanced EGFR (epidermal growth fae-tor responsive) positive adenocarcinoma were given either irinoteean 350 mg/m every 3 weeks and cetuximab 400 mg/m at week 2 then 250 mg/m eaeh week or cetuximab each week starting at week 1 and irinotecan starting at week 4. There was at least a 1 hour period between the end of the cetuximab infusion and the start of the irinotecan infusion. No evidence was found of a pharmacokinetic interaction between eetuximab and irinotecan, nor was there any significant increase in serious toxieities for the combination, when compared with treatment with either drug alone. ... [Pg.620]


See other pages where Cetuximab pharmacokinetics is mentioned: [Pg.530]    [Pg.356]    [Pg.371]    [Pg.413]    [Pg.207]    [Pg.1010]    [Pg.379]   
See also in sourсe #XX -- [ Pg.904 ]




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