Dexrazoxane Reduces Heart Damage Caused by Doxorubicin in Pediatric Acute Lymphoblastic Leukemia

Dexrazoxane Reduces Heart Damage Caused by Doxorubicin in Pediatric Acute Lymphoblastic Leukemia

According to a recent article published in The New England Journal of Medicine, the free-radical scavenger agent dexrazoxane reduces damage to the heart caused by the chemotherapy agent doxorubicin in children with acute lymphoblastic leukemia, without compromising the effectiveness of treatment.

Acute lymphoblastic leukemia (ALL) is a cancer of the bone marrow and lymph system. The bone marrow produces early blood-forming cells, called stem cells, which grow and mature into the three blood cell types: white blood cells, which fight infection; red blood cells, which carry oxygen to tissue; and platelets, which help blood to clot. ALL is characterized by uncontrolled production of immature lymphocytes (white blood cells), of which there are two types: B and T cells. These immature lymphocytes never mature enough to perform their specific function of fighting infection. In addition, these rapidly dividing cells crowd out and suppress the formation of other important blood cells, such as red blood cells, platelets and other white blood cells. ALL is an aggressive cancer that must be treated aggressively for optimal chances of a cure.

One commonly used chemotherapy agent in the treatment of ALL is doxorubicin (Adriamycin(R)). Unfortunately, one serious side effect of doxorubicin is damage to the cells in the heart. This side effect can leave permanent damage to the heart and/or may cause treatment disruption or termination of treatment with doxorubicin, leading to suboptimal treatment for the patient. Dexrazoxane is an agent that is a free-radical scanvenger, meaning that it inhibits the damaging effects of free radicals, often caused by chemotherapy, on healthy tissues. It is already approved by the FDA for the prevention or reduction of heart complications caused by doxorubicin in women with metastatic breast cancer.

A recent multi-institutional clinical trial was recently conducted to evaluate dexrazoxane in pediatric patients with ALL being treated with doxorubicin. This trial included 206 children, approximately half of whom were treated with dexrazoxane in addition to doxorubicin-containing therapy, and approximately half of whom received placebo (inactive substitute) in addition to their doxorubicin-containing therapy. Researchers measured levels of troponin T, a substance that can be found in the blood that is indicative of damage to heart cells when elevated. Elevations of troponin T occurred in only 21% of patients treated with dexrazoxane, compared with 50% of patients who received placebo. Extremely elevated troponin T levels occurred in only 10% of patients treated with dexrazoxane, compared with 32% of patients who received placebo. At nearly 3 years follow-up, there was no difference between survival or recurrences between the group of patients treated with dexrazoxane and the group of patients who received placebo, indicating that dexrazoxane does not interfere with the effectiveness of treatment for this group of patients.

The researchers concluded that dexrazoxane appears to reduce damaging side effects to the heart caused by the chemotherapy agent doxorubicin in the treatment of children with ALL, without compromising the effectiveness of treatment. However, the authors noted that longer follow-up is necessary to confirm the effects of dexrazoxane on long-term outcomes in this group of patients. Parents with children who have been diagnosed with ALL may wish to speak with their physician about the risks and benefits of dexrazoxane if their child is to receive doxorubicin-containing chemotherapy for their treatment.

Reference: Lipschultz S, Rifai N, Dalton V, et al. The effects of dexrazoxane on myocardial injury in doxorubicin-treatment children with acute lymphoblastic leukemia. The New England Journal of Medicine. 2004;351:145-153.

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