Cetuximab

Cetuximab Anti-EGFR Colorectal cancer, Head and Neck cancers... 

Cetuximab (Erbitux ) Merck mAb EGFR Metastatic colorectal cancer... 

Cetuximab specifically binds the extracellular domain of EGFR. It has been approved in colorectal and head and neck cancer. However, unlike for trastuzu-mab, no clear correlation has been demonstrated between EGFR expression in cancer cell and efficacy of cetuximab. 

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 (Erbitux) Chimeric antibody, IgGi EGFR Ligand competition ADCC CRC SSCHN... 

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. 

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. 

Erbitux (cetuximab chimaeric antibody raised ImClone Systems Treatment of EGF receptor-... 

Cetuximab is a chimeric monoclonal antibody directed against epidermal growth factor receptor. Common adverse events include acne-like skin rash, asthenia, lethargy, malaise, and fatigue. 

Oxaliplatin plus bimonthly infusional fluorouradl FOLFOX4rf Cetuximab Same as FOLFOX4 above Sensory neuropathy, neutropenia... 

Cetuximab plus irinotecan Continue irinotecan as previously dosed, plus cetuximab 400 mg/m2 IV loading dose, then cetuximab 250 mg/m2 Asthenia, diarrhea, nausea, acneiform rash,... 

Cetuximab, either alone or in combination with irinotecan, can be used in patients with disease progression on irinotecan. Cetuximab monotherapy can also be considered as salvage therapy in patients with oxaliplatin-refractory disease. 

Patients should be closely monitored for side effects that require aggressive intervention such as irinotecan-induced diarrhea and bevacizumab-induced GI perforation. Patients should be evaluated for other treatment-specific side effects such as oxaliplatin-induced neuropathy, cetuximab and panitumumab-induced skin rash, and bevacizumab-induced hypertension and proteinuria. 

In summary, these three approvals with the noncytotoxic monoclonal antibodies demonstrated activity based on survival (Avastin), TIP in an enriched population (Avastin in renal cell cancer), a pure response with endpoint (Campath), and a clever response rate to a combination vs. a reference point response rate with that new agent alone (Cetuximab). 

Bonner, J.A. et al., Cetuximab prolongs survival in patients with locoregionally advanced squamous cell carcinoma of head and neck a phase III study of high dose radiation therapy with or without cetuximab, Proc. Am. Soc. Clin. Oncol., 22, 489S, Abstr. 5507, 2004. McLaughlin, R et al., Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma half of patients respond to a four-dose treatment program, /. Clin. Oncol., 16, 2825-2833, 1998. 

Erbitux Cetuximab Bristol Myers Squibb, New York, NY /Imclone, New York, NY Anti-EGFR Colon cancer 2004... 

Cetuximab Erbitux Chimeric IgGl k anti-EGF receptor EGFR-expressing metastatic colorectal cancer 2003 Switzerland... 

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