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The chronic phase of chronic myelogenous leukemia (CML) can usually be controlled with certain chemotherapeutic drugs. These drugs include:

• Hydroxyurea
• Busulfan
• Interferon-alpha
• Imatinib mesylate (Gleevec)

Hydroxyurea

Until recently, oral therapy with hydroxyurea (Mylocel; Hydria; Droxia) was considered as a primary standard treatment for chronic-phase chronic myelogenous leukemia. Hydroxyurea is very effective in maintaining white blood cell counts in the normal range (good hematologic response) and controlling splenomegaly (enlargement of the spleen). Hydroxyurea, however, does not cure the underlying cause of chronic myelogenous leukemia (poor cytogenetic and molecular response).

Busulfan

Historically, busulfan (Myleran; Busulfex) was the first drug shown to produce a hematologic response in chronic myelogenous leukemia patients. Currently, the use of busulfan is limited to a preparatory regimen for chronic myelogenous leukemia patients undergoing allogeneic stem cell transplantation

Interferon-alpha

Interferons belong to a family of proteins that are produced and secreted by cells in response to viral infections. They serve to boost the immune system to attack and kill cells that are infected with a virus or cancer cells. Interferons are used to treat a variety of diseases including leukemias, lymphomas, and some other types of cancers.

Interferon-alpha (Roferon A; Alpha interferon; IFN) is used for the treatment of the chronic phase of chronic myelogenous leukemia and has been shown to prolong survival. It is not effective for the treatment of accelerated phase or blastic chronic myelogenous leukemia.Up to 80% of chronic myelogenous leukemia patients treated with Interferon-alpha achieve a complete hematologic response, however, only 5% to 25% will achieve a complete cytogenetic response. For this reason, Interferon-alpha is not considered as curative treatment for chronic myelogenous leukemia.

The results of randomized clinical trials have demonstrated that combination therapy with Interferon-alpha plus cytosine arabinoside (Ara-C) leads to an increased cytogenetic response and improves the survival of patients with chronic myelogenous leukemia.

A major drawback of Interferon-alpha therapy, which is administered by subcutaneous injection under the skin, is that it is associated with significant side-effects, including:

• Fatigue
• Chills
• Fever
• Weight loss
• Depression
• Aching muscles and joints

Imatinib Mesylate (Gleevec)

Imatinib mesylate (Gleevec) was approved by the U.S. Food and Drug Administration (FDA) in 2001 for the treatment of:

• Patients with chronic phase chronic myelogenous leukemia who have failed to respond to Interferon-alpha therapy
• Patients with accelerated phase chronic myelogenous leukemia
• Patients with blastic phase chronic myelogenous leukemia

Since receiving FDA approval, imatinib mesylate has had a dramatic impact on the treatment and prognosis of chronic myelogenous leukemia and has replaced both hydroxyurea and Interferon-alpha as the drug of choice for the treatment of chronic myelogenous leukemia.

Imatinib mesylate belongs to a category of novel anticancer drugs called tyrosine kinase inhibitors. The drug works by inhibiting the tyrosine kinase enzyme produced by the abnormal BCR-ABL fusion gene that causes the uncontrolled growth and proliferation of white blood cells that is characteristic of chronic myelogenous leukemia.

Several encouraging clinical trials have been conducted which demonstrated the efficacy of imatinib mesylate for the treatment of chronic myelogenous leukemia at various phases of the disease. In general, the results of these studies can be summarized as follows: