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Balancing oxaliplatin dose with neurological side effects in metastatic colon cancer

The drug oxaliplatin is a major reason the prognosis for metastatic colon cancer has gone from an expected survival of several months to a couple years. Unfortunately, the drug can also carry with it debilitating neurological side effects, which generally start as the sensation of pins and needles in fingers and toes and can leave patients unable to walk or dress independently.

However, "Many patients don't receive the necessary dose to try to keep their cancer in check, because their symptoms become too debilitating and their quality of life is reduced," says Andrew Weickhardt, MD, clinical fellow at the University of Colorado Cancer Center.

Weickhardt, along with Keith Wells, MD, and Wells Messersmith, MD, CU Cancer Center investigator and developmental therapeutics program co-leader, recently published a review in the Journal of Oncology that describes how to maximize the positives of this tricky balance between oxaliplatin's effects and side effects.

"Before, when patients died in a few months, these symptoms were overlooked. Now they're living two to three years and the symptoms deserve closer attention," Weickhardt says.

The review recommends two approaches, used alone or simultaneously what Weickhardt calls a "stop and go" approach, along with supplements that may mitigate the drug's neurological damage.

In the stop and go approach, a patient starts oxaliplatin along with another drug and takes both for two months. Then, the patient takes a hiatus from oxaliplatin (while continuing the first drug), and reintroduces oxaliplatin two months later or at the point of disease progression, whichever is sooner.

"After about six to nine months of total treatment, metastatic colorectal cancers tend to develop resistance to the drug," says Weickhardt. "And also, no matter what we do, after this same six to nine months of total treatment, neurological side effects start to rise." And so stop-and-go oxaliplatin dosing spreads the drug's effectiveness over the maximum possible time, with the fewest possible side effects.

Still, with this regimen, Weickhardt says that one in twenty patients experience significant nerve damage that can last for more than six months. "There's room for improvement," he says.

Though to date clinical trials of protective drugs given with oxaliplatin have been small, Weickhardt sees promise in the use of simple calcium and magnesium supplements.

"An infusion of calcium and magnesium should be used as well because they've shown some benefit and they don't do any harm," Weickhardt says. "They're popular in the community, and I'd encourage their use."

Contact: Garth Sundem
University of Colorado Denver

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