A platinum-based anticancer drug, oxaliplatin, has made great strides in recent years against colorectal cancer. Yet, it now appears that the drug causes possible permanent nerve damage that has the potential to worsen even months after treatment ends. The chemotherapy side effect was discovered by Johns Hopkins researchers in what may be the first attempt to trace oxaliplatin-based nerve damage through relatively inexpensive and simple punch skin biopsies, according to an article published in the September issue of Neurology.
The investigators stress that oxaliplatin undoubtedly lengthens patient survival in advanced cancer from months to years. Therefore, the goal of their new study is to determine ways of preventing or slowing the damage process through nerve-protective therapies discovered via simple skin testing.
To gain a deeper understanding of how nerve cells are affected by oxaliplatin, study leader Michael Polydefkis, MD, MHS, associate professor of neurology at the Johns Hopkins University School of Medicine and director of the EMG Laboratory and Cutaneous Nerve Laboratory at Johns Hopkins Bayview Medical Center, and his colleagues enlisted 8 patients with advanced colon cancer set to begin oxaliplatin treatment at The Johns Hopkins Hospital.
Each patient underwent a comprehensive neurological examination, including nerve conduction testing, a clinical exam to determine nerve damage, and a 3-mm diameter skin punch biopsy near their knees and ankles, before their first oxaliplatin infusion. Treatment consisted of oxaliplatin infusions over 2 days once every 2 weeks for 12 cycles. Once treatment began, researchers performed the same comprehensive tests after 30, 90 and 180 days of therapy. Additionally, 180 days after treatment was completed, the patients received one final exam.
Using a microscope, researchers viewed the degeneration of the nerve cells’ axons over the course of oxaliplatin therapy. Nerve function and neuropathy symptoms for each patients deteriorated over time. Interestingly, results from the punch skin biopsies neatly mirrored the side effect arc, and the degeneration persisted even after therapy ended. In fact, 180 days after their last oxaliplatin doses, the axons continued to decline in 7 of the 8 patients.
“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,” Polydefkis says. “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.”
Source: Johns Hopkins.