Targeted Therapy for Myelodysplastic Syndromes

A targeted therapy is one that is designed to treat the cancer cells and minimize damage to normal, healthy cells. Cancer treatments that “target” cancer cells may offer the advantage of reduced side effects and improved outcomes. 

Conventional cancer treatments cannot distinguish between cancer cells and healthy cells. Consequently, healthy cells are commonly damaged in the process of treating the cancer, which results in side effects. 

Chemotherapy damages rapidly dividing cells, a hallmark trait of cancer cells. In the process, healthy cells that are also rapidly dividing (such as blood cells and the cells lining the mouth and GI tract) are also damaged. Treatment-related damage to healthy cells leads to complications of treatment, or side effects. 

These side effects may be severe, reducing a patient's quality of life, compromising their ability to receive their full, prescribed treatment, and sometimes, limiting their chance for an optimal outcome from treatment. 

There are many different types of targeted therapies that work in a variety of ways. Revlimid® (lenalidomide) is the first to be FDA-approved for the treatment of only lower risk myelodysplastic syndrome (MDS) with a chromosome abnormality 5q- and transfusion dependence. Other targeted therapies are being evaluated in clinical trials. 

Lenalidomide - Lenalidomide is a new type of drug that regulates the immune system--called an immunomodulatory drug. Lenalidomide is thought to cause anticancer effects in a variety of ways, which include killing abnormal white blood cells, reducing inflammation, and inhibiting growth of new blood vessels. 

Clinical trial results demonstrate that lenalidomide is highly effective in the treatment of patients with low-risk MDS who are transfusion-dependent and who have a particular genetic abnormality, which is a partial loss of chromosome 5 (5q-). Response to treatment was rapid and long-lasting. Patients experienced an increase in hemoglobin, a component of red blood cells, within approximately 1 month (4.4 weeks) after the start of treatment. Two-thirds of the patients treated with lenalidomide did not require transfusions for nearly 1 year (47 weeks). 

Strategies to Improve Targeted Therapy of MDS 

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of MDS will result from the continued evaluation of new treatments in clinical trials. 

Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active investigation aimed at improving the treatment of MDS include the following: 

• Antithymocyte globulin (ATG) 
• Gleevec® (imatinib mesylate) 
• Zarnestra™ (tipifarnib) 
• New agents, such as clofarabine and cloretazine 

Imatinib mesylate - Imatinib is effective in patients with MDS who have an uncommon chromosomal abnormality involving a translocation of genetic material from chromosome 5, at a breakpoint in the long arm—5q33, to other chromosomes, e.g., t(5;12)(q33;p12-13).

Tipifarnib - Tipifarnib blocks a key enzyme (protein) called farnesyl transferase, which is involved in stimulating a cell to grow and replicate in an uncontrolled manner. In this way, tipifarnib slows down or stops the excessive replication of cancer cells. Tipifarnib appears to be an active treatment with limited side effects in the treatment of patients with intermediate or high-risk MDS.

New agents - Several are now being actively pursued in MDS, including clofarabine, cloretazine, and others.