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Colorectal Cancer Drug Implicated in Possible Permanent Nerve Damage

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Researchers at Johns Hopkins University have found that a popular anti-cancer drug called oxaliplatin, used to treat colorectal cancer, appears to cause nerve damage that worsens even after treatment ends, and may be permanent.

Many patients who take the drug report neurological side effects including pain in the hands and feet, numbness and tingling of the throat and difficulty swallowing.
In most cases the symptoms develop over time, but in some cases, the patient notices the effect from the moment the drug is infused.

The researchers wanted to know how the drug affects nerve cells so they recruited patients and gave them full neurological examinations to determine any nerve damage or confirm they were neurologically normal. They also had punch biopsies taken (tiny portions of skin removed from their knees and ankles). They were then given two infusions of oxaliplatin a day, over two days every fortnight (two weeks) for 12 cycles.

After this was completed, the researchers repeated the same neurological tests after 30, 90 and 180 days. At the end of the 180 days, the patients received a final checkup.

Their neurological function worsened over time. Using a microscope, the researchers saw that the nerve cells' long extensions, called axons, degenerated with use of the drug and this progressive degeneration continued even after the treatment was stopped. At the 180 day check (after the cessation of treatment), seven out of eight patient’s axons were still withering.

“This drug has rapidly become the standard of care for people with advanced colon cancer, but we really knew little about how oxaliplatin affects nerves over time,” said research leader Michael Polydefkis. “With people living longer lives on oxaliplatin, it’s important to know more about these neurological side effects so patients and their physicians can make educated choices on how this drug is used, and perhaps suggest ways to limit the damage.”

The study, published in Neurology, concluded, "This study demonstrates that oxaliplatin is associated with mild, sensory, and motor axon loss that may not be reversible.

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