Gleevec, What's the Story?
On the tenth year anniversary of the launch of Gleevec, the so-called “miracle” drug to treat leukemia, there is a controversy raging. US regulators from the Food and Drug Administration issued a letter to the manufacturer of Gleevec—Novartis AG—on April 21, warning them that they had websites that “are false and misleading because they promote the drug for an unapproved use, fail to disclose the risks associated with the use of Gleevec and make unsubstantiated dosing claims.” (Both websites are “temporarily unavailable.”) So what’s the story about Gleevec? What is the approved use of the drug, and what are the real risks?
Gleevec (imatinib mesylate) was approved for the treatment of newly diagnosed adult patients who have Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in the chronic phase. Ph+ CML is a slow-growing cancer of the blood and bone marrow. This form of leukemia begins when a young white blood cell accidentally makes an abnormal chromosome, called the Ph chromosome, which then makes a protein called Bcr-Abl. White blood cells that contain Bcr-Abl reproduce abnormally, and over time they crowd out normal blood cells. If not treated properly Ph+ CML can be life-threatening, but it is treatable.
Ph+ CML usually progresses to blast crisis phase if left untreated, so the goal of giving Gleevec to patients in the chronic phase is to prevent the disease from progressing to blast crisis. Gleevec is also approved for use in blast crisis, as well as accelerated phase, chronic phase after the patient has failed to respond to interferon-alpha therapy, relapsed or refractory Ph+ acute lymphoblastic leukemia, and several other similar types of leukemia as listed on the Gleevec website.
Gleevec is also approved for patients who have Kit-positive gastrointestinal stromal tumors (GIST) that cannot be removed surgically and/or have metastasized to other parts of the body. It is also administered to adult patients who have had their GISTs removed completely.
Kit+ GIST is a rare type of cancer that usually develops in the stomach or small intestine, although it can also form in other parts of the gastrointestinal tract. Kit is a protein found on the surface of normal cells that sends a signal that tells cells when to grow and divide. Kit+ GIST occurs when the protein keeps sending the signal and does not “turn off,” causing abnormal cells to keep growing and dividing and eventually becoming cancerous. Gleevec is administered to help stop these cells from growing and dividing.
Gleevec is not for everyone who may have one of these forms of leukemia. Among those adults who should not take Gleevec are women who are or could become pregnant, and women who are breastfeeding. Sexually active females should use birth control while taking Gleevec.
Most patients who take Gleevec can expect to experience side effects. Although most are mild to moderate in severity, they can be disruptive. Common side effects include fluid retention, muscle cramps or pain, abdominal pain, vomiting, diarrhea, abnormal bleeding, nausea, fatigue, and rash. Physicians can prescribe other medications to treat side effects, or the dose of Gleevec can be suspended or changed.
Serious side effects have also been reported by patients who have taken Gleevec. These include severe fluid retention that causes swelling around the eyes or swelling of the lower legs, lungs, and heart, resulting in death in rare cases; heart failure; liver problems; blistering of the skin; low levels of thyroid hormone; and low levels of certain blood cells.
Because Gleevec can cause stomach or intestinal irritation, the medication should be taken with food and a large glass of water to help minimize this reaction. In rare cases, Gleevec has caused a small tear or hole to develop in the stomach or intestinal tract, resulting in death.
Patients who plan to take Gleevec should also inform their doctor about any other medications they are already taking before they begin treatment with Gleevec. This includes over-the-counter and prescription drugs, as well as herbal remedies, and nutritional supplements (especially iron supplements). Patients should not consume grapefruit juice while taking Gleevec.
Consumers who are interested in reading more about the story of Gleevec and the complete prescribing information for the drug can do so online. Patients who are already using Gleevec and who have questions about their use of the drug should contact their prescribing physician.
Reuters, May 4, 2010