Those with severe chronic anemias need frequent blood transfusions to remain healthy, but such frequent transfusions can cause a potentially deadly buildup of iron in the body, leading to heart and liver failure. The traditional treatment to remove excess iron is so onerous that many patients choose to forgo it, putting their own lives at risk. The results of an international study on deferasirox, a new drug that may revolutionize the way chronic iron overload is treated, will be published in the May 1, 2006, issue of Blood, the official journal of the American Society of Hematology.
The current standard therapy to rid the body of excess iron is deferoxamine, administered for as long as the patient continues to receive blood transfusions, which, for many patients, can be for the rest of their lives. Although its effectiveness and safety are well-established, the necessity for the drug to be delivered by slow subcutaneous or intravenous infusion for eight to 12 hours a night over a period of five to seven days makes it an inconvenient and painful choice for patients. Unlike deferoxamine, deferasirox is available in a once-daily, drinkable format, providing a promising alternative.
"The ease and convenience of deferasirox means that more patients needing frequent blood transfusions, especially young children, will be able to be successfully treated and lead normal, healthy lives," said Maria Domenica Cappellini, MD, of the University of Milan, Italy, and lead study author.
To compare the efficacy and safety of the two drugs, a multicenter trial of both children (some as young as two years old) and adults diagnosed with chronic iron overload was conducted in a dozen countries worldwide. People with beta-thalassemia, an inherited blood disorder, were selected for this study because complications of chronic iron overload have been best studied in those with this disease. All participants continued receiving regular blood transfusions to treat beta-thalassemia throughout the year-long study.
Participants were randomized into two groups: 290 received deferoxamine infusions five days a week; 296 drank deferasirox dissolved in water each day before breakfast. Drug dosages were determined by each patient's liver iron concentration (LIC) level; those with higher levels received increased doses. Since LIC values above 7 mg Fe/g dw are associated with increased morbidity and mortality, the primary goal of the trial was to reduce LIC levels in those with high values and maintain LIC levels in those with low values. At the beginning of the study, more than two-thirds of the participants had at-risk LIC levels.
Deferasirox proved to be equally as effective as deferoxamine in patients receiving the highest doses of the drug. A majority of these patients (nearly 60 percent), demonstrated sustained or reduced LIC levels during the study. For those receiving the lowest drug doses, the amount of deferasirox was found to be insufficient in these regularly transfused thalassemia patients.
Deferasirox was generally well-tolerated. The most common side effects were skin rash (affecting approximately 11 percent of patients) and gastrointestional problems, which occurred in 15 percent of the group and included abdominal pain, vomiting, diarrhea, and constipation. Most patients (92 percent) were able to complete the study, though a small number in each treatment arm discontinued because of safety reasons. Four deaths, determined to be unrelated to the study drugs, also occurred during the trial.