Gleevec May Disrupt Ovarian Function
Benefits still outweigh potential infertility risks, experts say
By Serena Gordon
HealthDay Reporter
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(SOURCES: Constantinos Christopoulos, M.D., Ph.D., deputy director, 1st department of internal medicine, Amalia Fleming General Hospital, Athens, Greece; Jay Brooks, M.D., chairman, hematology/oncology, Ochsner Health System, Baton Rouge, La.; Bart Kamen, M.D., chief medical officer and executive vice president, Leukemia & Lymphoma Society, White Plains, N.Y., and professor, pediatrics and pharmacology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Piscataway, N.J.; March 6, 2008, New England Journal of Medicine)
WEDNESDAY, March 5 (HealthDay News) -- Although it's a much more targeted treatment than standard chemotherapy, the effective and much-touted leukemia drug, Gleevec, isn't without side effects.
In women still in their reproductive years, imatinib (Gleevec) might damage the chances of having a baby in the future, according to a case report published as a letter in the March 6 issue of the New England Journal of Medicine.
"Although the odds are not known, it is possible that imatinib and drugs with a similar mode of action may impair fertility," said one of the letter's authors, Dr. Constantinos Christopoulos, deputy director of the 1st department of internal medicine at Amalia Fleming General Hospital in Athens, Greece. "It is not known whether imatinib-induced infertility is reversible."
However, Christopoulos was also quick to point out that this was only a single case report of premature ovarian failure, and it can be difficult to establish the exact cause of the condition.
"Imatinib is a very effective drug that has revolutionized the treatment of chronic myeloid leukemia (CML), but knowledge of the effects of its long-term administration is still limited, and close medical surveillance of patients receiving the drug is mandatory," he said.
The patient Christopoulos and his colleagues reported on was a 28-year-old female who had Philadelphia chromosome-positive CML. Each year in the United States, just under 5,000 people are diagnosed with this type of cancer, according to the Leukemia and Lymphoma Society.
She was initially given 400 milligrams of Gleevec daily. About one year into her treatment, the dose of Gleevec was increased to 600 milligrams per day, because she still had some cancer cells. She didn't have any severe side effects due to the treatment, though she experienced some skin discoloration and muscle cramping. During the first two years, she also reported having regular menstrual cycles.
About two years after she first started taking Gleevec, and about six months after the dose was increased, the woman reported that she was having irregular menstrual cycles and then her periods ceased altogether.
Doctors confirmed premature ovarian failure. While it's not possible to definitively prove that Gleevec caused premature menopause, Christopoulos said that based on the timing, the lack of other causes, and the drugs' mode of action, it's the most likely culprit.
Gleevec works by targeting tyrosine kinases, which are proteins that are very active in cancer cells. However, these proteins are also expressed by the ovaries.
"There are about 60 tyrosine kinases. Can Gleevec be so specific that it only interacts with one of the 60? This drug is pretty good at targeting and hitting the bull's-eye, but it's not perfect," said Dr. Bart Kamen, chief medical officer of the Leukemia & Lymphoma Society.
"Is it worth that risk? You better believe it," Kamen said. "The side effects of Gleevec compared to what else we do in cancer treatment is mild. It has a wonderful risk-to-benefit ratio."
"The advantages of this drug clearly outweigh the disadvantages," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La.
Brooks also pointed out that most women with CML are long past their reproductive years. According to the American Cancer Society, the average age of CML diagnosis is about 67.
While most women are already counseled about the risks to their fertility before undergoing any cancer treatment, Christopoulos said that women of reproductive age receiving Gleevec should know that they shouldn't become pregnant while taking the drug, and they may want to freeze some of their eggs before treatment.
More information
The American Cancer Society has more on Gleevec. 
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