|
| Primary information |
|---|
| ID | 10005 |
| Therapeutic ID | Th1002 |
| Protein Name | Cetuximab |
| Sequence | >Th1002_Cetuximab
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYYDYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
|
| Molecular Weight | 145781.6 |
| Chemical Formula | C6484H10042N1732O2023S36 |
| Isoelectric Point | 8.48 |
| Hydrophobicity | -0.413 |
| Melting point | 71 |
| Half-life | 112 hours |
| Description | It is an epidermal growth factor receptor which binds to FAB region. Cetuximab consists of the variable antigen-binding regions of the 225 murine EGFr monoclonal antibody that is specific for N-terminal part of human EGFr with human IgG1 heavy chain and kappa light chain constant regions. |
| Indication/Disease | Used to treat EGFR-expressing metastatic colorectal cancer in patients resistant to irinotecan based chemotherapy regimens. Also used to treat squamous cell carcinoma of the head and neck in combination with radiation therapy. |
| Pharmacodynamics | Cetuximab specifically binds to the epidermal growth factor receptors (EGFr, HER1, c-ErbB-1) on both normal and tumor cells(EGFr is over-expressed in many colorectal cancers). Cetuximab competitively inhibits the binding of epidermal growth factor (EGF) and other ligands, such as transforming growth factor–alpha. Binding of cetuximab to the EGFr blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased matrix metalloproteinase secretion and reduced vascular endothelial growth factor production. |
| Mechanism of Action | Cetuximab binds to EGFr (over-expressed in many colorectal cancers) on both normal and tumor cells. Cetuximab competitively inhibits the binding of epidermal growth factor (EGF) and TGF alpha, thereby reducing their effects on cell growth and metastatic spread. |
| Toxicity | Single doses of cetuximab more than 500 mg/m2 have'nt been tested. There is no report of overdosage in human clinical trials. |
| Metabolism | Like other monoclonal antibodies, cetuximab is expected to undergo lysosomal degradation by the reticuloendothelial system and protein catabolism by a target‐mediated disposition pathway. |
| Absorption | After administration of a 400 mg/m2 initial dose followed by a 250 mg/m2 weekly dose, the steady-state levels of cetuximab was reached by the third weekly infusion with mean peak and trough concentrations across studies ranging from 168 µg/mL to 235 µg/mL and 41 µg/mL to 85 µg/mL, respectively.11 Tmax is about 3 hours. |
| 2-3 L/m2(Independent of dose) |
| Clearance | 0.103 L/h( In patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck) |
| Categories | Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Antineoplastic Agents, Immunological, Antineoplastic and Immunomodulating Agents, Blood Proteins, Cancer immunotherapy, Epidermal Growth Factor Receptor Antagonist, Globulins, HER1 Antagonists, Immunoglobulins, Immunoproteins, Immunotherapy, Narrow Therapeutic Index Drugs, Proteins, Serum Globulins |
| Patents Number | CA1340417 |
| Date of Issue | 2-Mar-1999 |
| Date of Expiry | 2-Mar-2016 |
| Drug Interaction | Thalomid (thalidomide) |
| Target | Epidermal growth factor receptor,Low affinity immunoglobulin gamma Fc region receptor III-B,Complement C1r subcomponent,Complement C1q subcomponent subunit A,Complement C1q subcomponent subunit B,Complement C1q subcomponent subunit C,Low affinity immunoglobulin gamma Fc region receptor III-A,Complement C1s subcomponent,High affinity immunoglobulin gamma Fc receptor I,Low affinity immunoglobulin gamma Fc region receptor II-a,Low affinity immunoglobulin gamma Fc region receptor II-b,Low affinity immunoglobulin gamma Fc region receptor II-c |
| Brand Name | Erbitux |
| Company | ImClone Systems Inc |
| Brand Description | ImClone Systems Inc |
| Prescribed For | Used for treatment of metastatic colorectal cancer (cancer spread beyond the colon or rectum) that over-expresses the epidermal growth factor receptor (EGFR). Aapproved for the treatment of squamous cell carcinoma of the head and neck. |
| Chemical Name | NA |
| Formulation | Formulated in a solution with no preservatives, which contains 8.48 mg/mL sodium chloride, 1.88 mg/mL sodium phosphate dibasic heptahydrate, 0.41 mg/mL sodium phosphate monobasic monohydrate, and Water for Injection, USP. |
| Physical Appearance | Sterile, clear, colorless liquid of pH 7.0-7.4, which may contain a small amount of easily visible, white, amorphous cetuximab particulates |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | Generally given once every week for 6 to 7 weeks. And supplied at a concentration of 2 mg/mL in either 100 mg (50 mL) or 200 mg (100 mL), single-use vials. |
| Contraindication | allergic |
| Side Effects | Rash (Acne like), Generalized weakness, malaise, Fever, Low magnesium level are commom (occurring in greater than 30%) for patients taking Erbitux. And less coomon side effects (occurring in about 10-29%) of patients receiving Erbitux are; Nausea and vomitting. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |