French doctors have are now reporting a possible new side effect linked to Gleevec. Gleevec, generically known as imatinib, is a cancer drug most commonly used in the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Earlier this year, a case report by Greek doctors suggested that imatinib may disrupt ovarian function and impair fertility.
The French report appears in a letter published in the June 19 issue of the New England Journal of Medicine, wherein the doctors describe the case of a 25-year-old woman who developed severe rhabdomyolysis while taking imatinib. The Greek report was published as a letter in an earlier issue of the New England Journal of Medicine.
Rhabdomyolysis is the breakdown of muscle fibers that causes in the release of muscle fiber contents—known as myoglobin—to leak into the bloodstream. Rhabdomyolysis can be harmful to the kidneys and can cause kidney damage.
The 25-year-old woman cited in the French research was taking a daily 400 mg dose of Gleevec as part of a clinical trial for the treatment of aggressive fibromatosis–desmoid tumors—that could not be treated with surgery. Shortly after she began a course of drug treament with Gleevec, the woman began to experience the symptoms of rhabdomyolysis. Once she discontinued use of Gleevec, the woman’s adverse reactions to the drug ceased. As part of the clinical trial, the woman agreed to re-start the Gleevec treatment while under medical surveillance. Twenty-four hours after she received the first daily dose of 100 mg, she suffered severe symptoms. The drug treatment was halted, and her symptoms disappeared in three days. The woman’s desmoid tumors were then treated with radiotherapy and she has not experienced any recurrence of rhabdomyolysis symptoms.
“We considered our patient’s rhabdomyolysis to be induced by imatinib because of the temporal relationship (the rhabdomyolysis occurred within a few days after the initiation of imatinib therapy), the recurrence of rhabdomyolysis with the reintroduction of the drug, and normalization of the creatine kinase level after discontinuation of the drug. Although there is extensive clinical experience with the safe use of imatinib, this observation suggests that the drug may cause severe rhabdomyolysis in a small proportion of patients,” the doctors wrote.
When muscle is damaged, as in rhabdomyolysis, a protein pigment called myoglobin is released into the body’s bloodstream and is then filtered out of the body by the kidneys. Myoglobin breaks down into potentially harmful compounds and may block the structures of the kidney, which can cause serious damage such as acute tubular necrosis or kidney failure. Dead muscle tissue may also cause a large amount of fluid to move from the blood into the muscle, which reduces the fluid volume of the body and can lead to shock and reduced blood flow to the kidneys. Symptoms of rhabdomyolysis include abnormal urine color, which can be dark, red, or brown in color; general weakness, muscle stiffness or aching, also known as myalgia; muscle tenderness; fatigue; joint pain; seizures; and unintentional weight gain.
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