Cancer treatments cetuximab

Note that application in the particular indications is usually restricted either to patients expressing the target (e.g. trastuzumab, cetuximab, lapatinib, imatinib) and/or after failure of prior therapies (e.g. cetuximab, erlotinib, lapatinib, sutinib, dasatinib). Furthermore, for cancer treatment most tyrosine kinase inhibitors are applied in combination with conventional chemotherapeutic drugs, such as fluorouracil, taxanes, platin-based regimens, anthracylines and irinotecan or radiotherapy. 

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. 

In metastatic colorectal cancer treatment, two agents were approved almost simultaneously, cetuximab and bevacizumab. 

ADCC. Cetuximab is approved for treatment of metastatic colorectal cancer (CRC) and squamous cell carcinoma of the head and neck (SCCHN). Interestingly, an adverse event, acneiform rash seems to correlate with a better response to cetuximab, while there is no such correlation with expression levels of EGFR assessed by immunohistochemistry. Further side effects are rare infusion reactions and hypomagnesia. Two other anti-EGFR antibodies approved for clinical use are the fully human antibody panitumumab (Vectibix)... 

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. 

Cetuximab (Erbitux) is a monoclonal antibody against the epidermal growth factor receptor, EGFR. It is approved for treatment of colorectal cancer. The development of Erbitux was much in the news in 2004 as a result of insider stock trading at ImClone in the face of an initial turndown by the FDA. The former head of ImClone, Sam Waksal, is spending a term of 7 years in jail for his role in the affair. Martha Stewart completed a jail term of several months in the same case. Erbitux was subsequently approved by the FDA on the basis of additional clinical information. 

Reynolds NA, Wagstaff AJ. Cetuximab in the treatment of metastatic colorectal cancer. Drugs 2004 64 109-18. 

Cetuximab is a chimeric monoclonal antibody, against epidermal growth factor receptor (EGFR). It is given by intravenous injection with weekly intervals for the treatment of metastatic colorectal cancer and head and neck cancer. It is given in combination with the chemotherapeutic agent irinotecan. The... 

Cetuximab is indicated for the treatment of head, neck and colorectal cancers, and in combination with radiation therapy it is used for the treatment of squamous cell carcinoma (locally or regionally advanced) of the head and neck. However, in patients with recurrent or metastatic squamous cell carcinoma of the head and neck whose response to the previous platinum-based therapy has not been positive, it is not given in combination with radiation therapy and is administered alone. Generally, a dose of 400 mg/m2 is initially administered in combination with radiation therapy followed by a maintenance dose of 250 mg/m2 and is administered 1 h... 

Cetuximab is used for treatment of metastatic colorectal carcinoma, which expresses EGFR, in combination with irinotecan, provided that these patients are refractory to irinotecan-based standard chemotherapeutic regimen. However, in patients who could not tolerate irinotecan-based chemotherapeutic regimen, it is used as a single treatment for EGFR-expressing metastatic colorectal cancer. The doses are similar to the doses used for squamous cell carcinoma of the head and neck. 

Currently, cetuximab (Erbitux ) is indicated for the treatment of patients with EGFR-expressing metastatic colorectal cancer after failure of irinotecan-including cytotoxic therapy. Depending on the country, cetuximab is approved in combination with irinotecan or in addition as monotherapy. The approved dosing regimen consists of an initial dose of 400 mg/m2 body surface area (BSA), followed by weekly doses of 250 mg/m2. The (intravenous IV) infusion durations are 2 h for the initial infusion, and 1 h for the subsequent weekly infusions. 

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. 

Van Cutsem E et al. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC) The CRYSTAL trial. Journal of Clinical Oncology (Meeting Abstracts) 2007 25 4000. 

Jonker D et al. Cetuximab for the treatment of colorectal cancer. The New England Journal of Medicine 2007 357 2040-2048. 

Wu G, Yang W, B arth RF et al. Molecular targeting and treatment of an epidermal growth factor receptor-positive gfioma using boronated cetuximab. Clin. Cancer Res. 2007 13 1260-1268. 

In a phase II study of cetuximab and radiation in elderly and/or poor performance status patients with locally advanced non-small-cell lung cancer, there were no treatment-related deaths, but 31 patients had grade 3 or worse adverse events, most commonly/flf/gMe, anorexia, dyspnea, rashes, and dysphagia, each of which occurred in under 10% of patients [107 ]. 

Skin Skin reactions are the most common adverse reactions during cetuximab therapy for malignancy, and rashes after treatment with cetuximab are associated with better outcomes in patients with non-small-cell lung cancers [110 ]. Patients who developed acne-like rashes within the first 3 weeks of treatment with chemotherapy + cetuximab hved significantly longer and had better progression-free survival and a higher response rate [111 ]. 

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