FDA Approves STI157 Efficacy for Chronic Myelogenous Leukemia

The FDA has recently approved STI571 for the treatment of chronic myeloid leukemia.

Chronic myeloid leukemia (CML), also called chronic granulocytic leukemia, is a cancer of the white blood cells. The bone marrow contains early blood-forming cells called stem cells, which grow and mature into 3 blood cell types: red blood cells, which provide oxygen to tissues; platelets, which aid in blood clotting; and white blood cells, which fight infection. In the case of CML, large numbers of young granulocytes (a type of white blood cell) do not mature, resulting in an excess accumulation of these cells. These leukemia cells then crowd the bone marrow and blood, suppressing formation and function of other blood cells normally present in these areas. In addition, the leukemia cells cannot perform their function in the body properly, leaving patients susceptible to infection.

CML begins with a chronic phase, during which few clinical problems, if any, present themselves. However, if left untreated, the chronic phase can progress into acute phases, characterized by fast-growing and aggressive cancer. These phases are called the accelerated and blastic phases. Patients reaching these acute phases have a poor prognosis for long-term survival. Thus, it is imperative to treat this leukemia as early as possible, while it is in a less aggressive phase.

The majority of CML cases are caused by a specific genetic abnormality, referred to as the Philadelphia chromosome. The Philadelphia chromosome occurs through a switching of specific genetic information. The result of this genetic switching produces a protein called the

Bcr-Abl tyrosine kinase. The Bcr-Abl tyrosine kinase protein facilitates cellular function and growth by modulating certain chemical information flow into and out of cells, and initiating growth responses to chemical stimuli. The pivotal problem with Bcr-Abl tyrosine kinase is that it performs its functions in an uncontrolled manner, leading to excessive replication and growth of cells – the hallmark trait of cancer.

High-dose chemotherapy followed by an allogeneic stem cell transplant is considered a curative treatment option for patients with CML. However, a large percentage of CML patients are not able to tolerate this procedure. For these patients, many treatment options assist in controlling CML and prolonging survival, such as chemotherapy, radiation therapy, and biologic therapies (utilizing the body’s immune system to kill the cancer). Since these therapies are not considered curative, research efforts have been ongoing in an attempt to develop novel CML therapies with curative intent that can be tolerated by the majority of patients.

STI571 is a new type of therapy that has demonstrated high rates of anti-cancer responses in Philadelphia chromosome-positive CML patients in all phases who are no longer responding to standard therapies. STI571 produces its effects by binding to a specific site on the Bcr-Abl tyrosine kinase. The binding of STI571 blocks the growth effects facilitated by Bcr-Abl. This, in turn, halts the excessive replication and growth of cancer cells. Moreover, since STI571 only binds to cancer cells, side effects are minimal.

Two separate clinical trials were recently performed to further evaluate STI571 in the treatment of CML. The first trial involved 54 CML patients in the chronic phase who had failed conventional treatment. Within the first month of therapy, all but one patient had no evidence of cancer in their blood. Approximately 54% of patients showed cytogenetic (chromosomal) responses. The second trial involved 38 CML patients in the blastic phase, with approximately 55% of these patients showing an anti-cancer response to treatment. Seven patients continue to receive STI571 and remain in remission from 100 days to one year following initial STI571 treatment. STI571 was well tolerated and produced few side effects in patients involved in both of these trials.

These results support findings from previous clinical trials designed to evaluate STI571 and indicate the effectiveness of this agent in the treatment of CML. These trials prompted the FDA to approve STI571 for the treatment of all stages of CML. Individuals with CML may wish to speak with their physician about the risks and benefits of STI571.

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