Colorectal cancer drug linked with nerve damage

Oxaliplatin, a platinum-based anticancer agent that has become the standard of care for people with advanced colorectal cancer, appears to cause nerve damage that may be permanent and worsens even months after treatment ends.

These were the conclusions of a team led by Michael Polydefkis, MD, MHS, an associate professor of neurology at Johns Hopkins University School of Medicine and the director of the EMG Laboratory and Cutaneous Nerve Laboratory at Johns Hopkins Bayview Medical Center, both located in Baltimore, Maryland. However, the investigators emphasize that the agent clearly improves length of survival in advanced cancer by months to years, and their goal is to find ways of preventing or slowing the damage through nerve-protective therapies identified through simple skin testing.

Polydefkis and colleagues studied eight people with advanced colorectal cancer in order to characterize the natural history of oxaliplatin-associated neuropathy. In a statement describing the team's findings, Polydefkis explained that users of the drug report bothersome neurologic side effects, including pain in the hands and feet and numbness or tingling in the throat that affects swallowing.

The participants were followed prior to starting chemotherapy with oxaliplatin. At baseline and at 30, 90, 180, and 360 days (180 days after completing treatment), they underwent electrophysiology, punch biopsies, symptom assessment, and examinations with calculation of a reduced total neuropathy score (rTNS).

Test results showed that in each patient, nerve function and neuropathy symptoms worsened over time. For example, distal leg intraepidermal nerve fiber density (IENFD)—a sensitive measure of neuropathy progression—as well as rTNS were significantly reduced over time. Measures of axon loss continued to worsen following discontinuation of oxaliplatin. Five of the patients reported prominent symptoms associated with the use of oxaliplatin.

The findings indicate that oxaliplatin is associated with mild, sensory, and motor axon loss that may not be reversible, according to the authors' report in Neurology (2011;77[10]:980-986). The results also strongly suggest that punch skin biopsies could be an easy and inexpensive way to follow nerve cell degeneration.

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