Imatinib is a tyrosine kinase inhibitor used primarily to treat chronic myeloid leukemia. It achieves good results in the treatment of chronic myeloid leukemia while being well tolerated. Its use in other malignancies is also possible.
What is imatinib?
Imatinib (trade name Gleevec) is a drug in the tyrosine kinase inhibitor group used to treat chronic myeloid leukemia, malignant tumors of the gastrointestinal tract, and other malignancies. The chemical molecular formula of imatininb is C29H31N7O.
Pharmacologic action
Chronic myeloid leukemia is caused by the so-called Philadelphia chromosome, a genetic alteration. In the Philadelphia chromosome, there is a translocation of genetic material from chromosome 9 and chromosome 22. As a result of this translocation, the gene for the natural enzyme tyrokinase-ABL on chromosome 9 “fuses” with the fragment of the BCR gene on chromosome 22. The cells mutated as a result produce a so-called fusion protein BCR-ABL instead of the tyrosine kinase ABL. BCR-ABL is a more active tyrosine kinase compared to ABL. This BCR-ABL leads to uncontrolled proliferation of white blood cells (leukocytes) and is significantly involved in the development of chronic myeloid leukemia. Imatinib has an inhibitory effect on the activity of tyrosine kinase and thus suppresses the pathological increased proliferation of the mutated blood stem cells. The substance is administered orally in the form of a tablet; imatinib mesilate, a salt, is used medicinally. The goal of treatment is to reduce the pathological cell clone as much as possible. Normalization of the blood count is achieved in more than 95% of patients treated with imatinib who had chronic myeloid leukemia.
Medical Application and Use
The substance is used primarily in the treatment of chronic myeloid leukemia, as mentioned above. However, it is also effective against a number of other cancers. For example, it is also indicated in acute lymphoblastic leukemia, hypereosinophilic syndrome, various tumors of the skin, malignant tumors of the gastrointestinal tract, aggressive mastocytosis, and certain myeloproliferative disorders. In chronic myeloid leukemia, a neoplastic disease of the hematopoietic system, there are increased immature forms of leukocytes in the blood due to pathologically increased proliferation of leukocytes in the blood and hematopoietic bone marrow. Chronic myeloid leukemia results from a (genetic) disorder of the hematopoietic (blood-forming) stem cells found in the bone marrow. For this reason, chronic myeloid leukemia belongs to the group of myeloproliferative neoplasms. The cause of the disease is the alteration and subsequent proliferation of a single multipotent hematopoietic progenitor cell. In almost all cases, this alteration is due to the Philadelphia chromosome, which has already been described. Novel drugs from the group of tyrosine kinase inhibitors, which includes imatinib, have significantly improved the prognosis of chronic myeloid leukemia. Therapy with tyrosine kinase inhibitors is a highly effective treatment option with relatively few side effects and is considered targeted therapy. Survival rates have greatly increased with the introduction of tyrosine kinase inhibitors. When there were no therapeutic options for chronic myeloid leukemia, the median survival time of patients was between three and four years. Chronic myeloid leukemia was the disease with the worst prognosis from the group of myeloproliferative neoplasms. The introduction of hydroxycarbamide, a cytostatic agent, increased this median survival to four and a half years. Interferon led to a further increase in median survival to approximately five and a half years. Now, treatment with tyrosine kinase inhibitors is considered standard therapy. The 5-year survival rate with imatinib treatment is over 90%. The follow-up time of patients treated with imatinib is now more than 10 years; the “median survival” has not yet been established.This suggests that it is very significantly higher than the median survival of previously used therapies (with hydroxycarbamide and interferon).
Risks and side effects
Imatinib is generally well tolerated. However, diarrhea, vomiting, abdominal pain, nausea, indigestion, fatigue, headache, edema, weight gain, muscle cramps, muscle aches, joint pain, skin rash, bone pain, and changes in blood counts may occur. Imatinib is contraindicated only in cases of hypersensitivity or intolerance to imatinib. Imatinib should not be taken concomitantly with acetaminophen because it inhibits the glucuronidation (binding to glucuronic acid during metabolism) of acetaminophen. Furthermore, certain subunits of cytochrome P450 are affected, which may lead to interactions with other drugs.
