Nimotuzumab
From Wikipedia, the free encyclopedia
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Nimotuzumab?
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| Therapeutic monoclonal antibody | |
| Source | Human |
| Target | EGFR |
| Identifiers | |
| CAS number | |
| ATC code | ? |
| PubChem | ? |
| Chemical data | |
| Formula | C6566H10082N1746O2056S40 |
| Mol. mass | 151,000 Daltons[1] |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status |
?(CA) |
| Routes | ? |
[edit] Introduction
Nimotuzumab is a humanized monoclonal antibody used to treat cancer. It was developed at the Center of molecular immunology (CIM) in Havana, Cuba.[2] Nimotuzumab binds with intermediate affinity and high specificity to the extracellular region of EGFR (epithelial growth factor receptor). This results in a blockade of ligand binding and receptor activation.[3][4] Epidermal growth factor receptor (EGFR) is a key target in the development of cancer therapeutics. EGFR-targeting drugs have been shown to improve response when used with conventional treatments such as radiation therapy and chemotherapy.
The Center of molecular immunology with YM Biosciences and its licensees are committed to the clinical development and subsequent marketing of nimotuzumab. These include Daiichi-Sankyo Co. Ltd. in Japan, Oncoscience AG in Europe, Kuhnil Pharmaceutical Co., Ltd. in South Korea and Innogene Kalbiotech Pte Ltd. in South East Asia. In addition, as of November 30, 2007 eight other companies around the globe were involved either in a consortium with YM, its licensees or certain of the other licensees, or unilaterally in a number of trials in multiple indications. The other licensees for nimotuzumab include Biocon BioPharmaceuticals Ltd. (BBPL) in India, Biotech Pharmceutical Co. Ltd. in China, Delta Laboratories in Colombia, Eske Group in Peru, Eurofarma Laboratorios Ltda. in Brazil, Ferozsons Labs in Pakistan, Laboratorio Elea S.A.C.I.F.yA. in Argentina and Laboratorios PiSA in Mexico.
Nimotuzumab has been administered to >1,800 patients worldwide through clinical trials, compassionate use programs and commercial sales. To date (11/June/2008)[5], there have been no reports of any severe incidents of skin rash or other side-effects commonly observed with EGFR-targeting monoclonal antibodies or small molecule inhibitors.
[edit] Safety Profile
The toxicity and safety of nimotuzumab have been assessed in several pre-clinical and clinical studies.
Safety in pre-clinical experiments:
- Nimotuzumab did not produce any significant acute toxicity following single administration of up to 10 times the dose proposed for clinical trials.
- No treatment-related systemic toxicity was observed in animals after administering nimotuzumab once daily for 14 days.[6]
Safety profile in clinical trials
Nimotuzumab has been found to be very well tolerated in clinical trials. Common adverse reactions seen in patients treated with nimotuzumab include:
- Chills
- Fever
- Nausea and vomiting
- Dryness of mouth
- Asthenia
- Hypertension/hypotension
- Flushing
All adverse events were mild to moderate and were considered infusion reactions. No patient developed acneiform rash or other dermatological toxicity.[7] Grade 3 somnolence was reported in one patient following a 400 mg dose of nimotuzumab.[8]
In a phase II trial, the most common adverse reactions were fever (4.28%), dizziness and hypotension (2.86%) and mild skin rash (1.43%).[9]
These adverse reactions respond to treatment with conventional doses of analgesic and antihistaminics.[10]
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[edit] Notes
- ^ Investigator Brochure. TheraCIM h-R3 (YMB1000). YM BioSciences Inc. Mississauga: ON. 2005
- ^ Mateo C, Moreno E, Amour K, Lombardero J, Harris W, Pérez R. Humanization of a mouse monoclonal antibody that blocks the epidermal growth factor receptor: Recovery of antagonistic activity. Immunotechnology 1997;3:71-81
- ^ Ramos TC, Parada AC, Escobar NI. h-R3. Drugs Future. 2003;28(suppl 9):847-853
- ^ Investigator Brochure. TheraCIM h-R3 (YMB1000). YM BioSciences Inc. Mississauga: ON. 2005
- ^ www.nimotuzumab.com
- ^ Ramos TC, Parada AC, Escobar NI. h-R3. Drugs Future. 2003;28(suppl 9):847-853
- ^ Crombet T, Torres L, Neninger E, et al. Pharmacological evaluation of humanized anti-epidermal growth factor receptor, monoclonal antibody h-R3, in patients with advanced epithelial-derived cancer. J Immunother.2003;26:139-148
- ^ Crombet TR, Osorio M, Cruz T, et al. Use of humanized anti-epidermal growth factor receptor monoclonal antobody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients. J Clin Oncol.2004;22:1-9
- ^ Guozhen X, Li G. Phase II trial of recombinant humanized anti-human epidermal growth fator receptor monoclonal antibody (h-R3). Tumour hospital, China Academy of Medical Science. 2004:1-72
- ^ TheraCIM h-R3 [package insert]. Havana City, Cuba: CIMAB S.A.
