New drug approved for chronic myeloid leukemia
By William T. Elliott, MD, FACP
and James Chan, PharmD, PhD
Imatinib (Gleevec) has been approved for the treatment of chronic myeloid leukemia (CML). The drug is considered a major breakthrough in oncologic therapy, and its approval was heralded with much fanfare, which included a cover story in Time magazine. The drug is revolutionary because it targets the molecular understructure of cancer cells and leaves healthy cells alone. The drug was approved by the Food and Drug Administration (FDA) less than three months after application.
• Clinical implications.
CML is a clonal disorder characterized by leukocytosis and the presence of immature white blood cells in the peripheral blood and hypercellular marrow with myeloid hyperplasia in the bone marrow. It is estimated that there are about 25,000 people in the United States with the disease. CML generally progresses through a chronic phase, accelerated phase, and blast crisis (acute leukemia), with median survival about six years. Current therapies — all with limitations — include allogeneic bone marrow transplantation, chemotherapy (e.g., hydroxyurea), and interferon-alfa with or without cytarabine. Imatinib provides a breakthrough treatment for CML compared to interferon.
• Dosage.
The recommended dose of imatinib is 400 mg daily for patients in chronic phase CML and 600 mg daily for patients with accelerated phase or blast crisis. The dose may be increased if there is disease progression, inadequate hematologic response after three months of therapy, or the loss of a previously achieved response. For patients with chronic phase CML, the dose may be increased from 400 mg daily to 600 mg daily if tolerated (i.e., absence of severe adverse hematologic or nonhematologic reactions). For patients with accelerated phase or blast crisis, the dose may be increased from 600 mg to 800 mg (400 mg twice daily).1 The drug should be taken with a meal and with a large glass of water to reduce gastrointestinal irritation. Imatinib is supplied as 100 mg capsules.
• Nursing considerations.
Imatinib is indicated for the treatment of patients with CML in blast crisis, accelerated phase, or in chronic phase after failure with interferon therapy.1 Imatinib appears to have significant advantages over current therapies for CML in a better and more rapid response and fewer adverse effects, and it can be given orally.2,3 It also appears to be effective in patients who have failed interferon therapy.4 Imatinib should be continued as long as it remains effective. The dose should be adjusted or withheld if severe nonhematologic adverse reactions (hepatotoxicity or fluid retention) or severe hematologic adverse reactions (neutropenia or thrombocytopenia) occur. Complete blood counts should be performed weekly for the first month and biweekly for the second month of therapy, and every two to three months thereafter.1
The most frequent side effects are nausea (55%-68%), vomiting (28%-54%), fluid retention (52%-58%), diarrhea (33%-49%), and muscle cramps (25-46%). Severe fluid retention (e.g., pleural effusion, pericardial effusion, pulmonary edema, and ascites) has been reported in 1%-2% of patients and increases with higher imatinib dose and age older than 65 years. Severe superficial edema has been reported in 1%-3% of patients. Cytopenias are more frequent with patients with accelerated CML or blast crisis than with chronic phase CML. Severe elevation of transaminases or bilirubin also can occur, and the patients should be monitored at baseline and monthly or as clinically indicated.1
• Patient education.
Patients should be helped to understand that although imatinib shows great promise and is directed at the abnormal "target" in CML, it is not a cure, is not completely effective, and does have side effects. Due to the expedited FDA approval and limited follow-up time, toxicities as a result of long-term use are not known.1 The drug is extremely expensive. Monthly cost is about $2,400, and annual cost is about $30,000. However, Novartis will provide assistance to uninsured patients by providing the drug free to those with an annual income below $43,000 and on a sliding scale for those uninsured patients whose annual income is $43,000-$100,000.5
References
1. Gleevec Product Information. Novartis Pharmaceutical Corp. May 2001.
2. Goldman JM, JV Melo. N Engl J Med 2001; 344:1,084-1,086.
3. Druker BJ, et al. N Engl J Med 2001; 344:1,038-1,042.
4. Druker BJ, et al. N Engl J Med 2001; 344:1,031-1,037.
5. FDC Report. The Pink Sheet 2001; 63:3-4.
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