Imatinib (Glivec)

Mechanism of action:
Imatinib (Glivec) works by blocking cell signals essential for growth and division of cancer cells. Imatinib specifically inhibits the enzyme tyrosine kinase involved in signal transduction, hence it is related to a class of medications knows as tyrosine kinase inhibitors.

In chronic myelogenous leukemia CML, the translocation between chromosome 9 and 22, t (9;22) the so called Philadelphia chromosome is the key in malignant transformation of myeloid cells. This translocation results in a fusion protein, which acts a continuously active tyrosine kinase. Imatinib blocks the ATP mediated phosphorylation activation of this enzyme.
 

Imatinib also inhibits the tyrosine kinase product from other cancer cells like the c-kit in cases of a rare form of gastrointestinal tumors known as Gastrointestinal Stromal tumors GISTs.
 

Uses:
Imatinib is used in the treatment of CML, GISTs and Dermatofibrosarcoma protuberans.
 

Duration of treatment:
Duration of treatment is still investigational and till today Imatinib is given to patients who benefit until disease progression.
 

Dose and administration:
It is available as 100 mg and 400mg tablets or capsules. In CML patients, Imatinib is normally given once daily at a dose of 400 mg/day in cases of chronic phase and 600mg/day in cases of accelerated disease state. When there is failure to achieve a satisfactory hematologic response after at least 3 months of treatment and or disease progression at anytime, doses can increase from 400 to 600 in cases of CML in chronic phase and from 600 to 800 mg/day in cases of CML in accelerated phase as tolerability allows. Otherwise patients shift to another treatment option.
 

Metabolism and excretion:
The drug is metabolized mainly in the liver and excreted in bile.
 

Toxicity:
The long term effects of this drug is still to discovered together with its effect on the fetous. In general, the drug is proved to be safe tolerable with mild toxicity.
 

Common forms of side effects include:
Nausea, Diarrhea and loss of appetite
Headaches, Leg pain & cramps and generalized edema due to fluid retention
Visual disturbances and skin rash.

Symptoms related to anemia (dyspnea, dizziness and headache), leucopenia (recurrent infections and fever) and Low platelet count (bruise).
 

Refrences:

The information contained in this page is provides based on reliable sources like the FDA website and the NCCN guidelines.