Vistonuridine Rescues Patients From Potentially Fatal 5-Fu Overdose

An overdose of fluorouracil (5-Fu) can kill you. Or a proper dose of fluorouracil, pumped too quickly into your bloodstream, can also be fatal. Fluorouracil (5-Fu) is a chemotherapy drug used to treat solid tumors such as breast cancer. It's a tricky drug to use, because it has be be given at a near-toxic dose, along with other powerful drugs, to kill cancer cells. So your oncologist has to carefully calculate your dose, balance the effects of the 5-Fu with your other drugs, and then use an infusion pump working at an ideal rate, to give you a treatment. I've never checked to see if my oncologist crossed his fingers or said a little prayer each time he sent a patient into the infusion room for a treatment that included 5-Fu, but I wish he would.

In addition to all these calculations, calibrated pumps, and crossed fingers, there is now a drug that can be used to rescue you, if you are accidentally given too much 5-Fu. This new drug is vistonuridine, a 5-Fu antidote that is being developed by Wellstat Therapeutics. At the upcoming American Society of Clinical Oncology (ASCO), clinical data will be presented on 17 cases of fluorouracil overdose for which potential death was averted by the emergency use of vistonuridine. The good news is that all 17 patients treated with vistonuridine for their 5-Fu overdose did recover, and the bad news is that in a different group of 13 patients with a 5-Fu overdose who did not receive vistonuridine, only two patients survived.

The majority of patients who take 5-Fu have no serious reactions to it, other than neutropenia, diarrhea, nausea, vomiting, and mucositis. But each patient is different, and some of us can't process 5-Fu and get rid of it fast enough to avoid more severe side effects. Oncologists don't always know who can tolerate 5-Fu well, but researchers are developing a severity score tool that would help predict your reaction before giving you a dose of chemo. Hurrah for personalized medicine!

Now why do overdoses of 5-Fu occur? Well, infusion pumps sometimes misfunction, or a nurse might accidentally program it wrong, your oncologist might miscalculate your dose, or some of your other drugs might interact badly with the 5-Fu. Still, the National Institutes of Health estimates that less than three percent of all patient who take 5-Fu will develop a fatal toxic reaction to it - so don't panic if your doctor prescribes this drug.

Vistonuridine is still considered an investigational drug that can be given under emergency-use Investigational New Drug provisions of the Food and Drug Administration (FDA). When a 5-Fu overdose is diagnosed, your oncologist would have to request the vistonuridine for you, and it would be delivered as quickly as possible. “Because no antidote for 5-FU overexposure is approved today, we have been responding to emergency requests for vistonuridine,” said Michael Bamat, Vice President, Research and Development, Wellstat. “The data support the life-saving potential of this agent in cases of 5-FU overdose, and we plan to seek regulatory approval in the US and Europe.”

I will never know if 5-Fu was the drug that landed me in the hospital at 2am after my third chemo treatment, blue and gasping for breath, weak enough to require a wheelchair, feeling about 180 years old. I was given a transfusion of three pints of blood, and kept in the hospital for a couple of days. It was a month before I could go back to work. My oncologist at the time said that only about three percent of all his patients ever had such a reaction to chemo (sound familiar?) and he wasn't sure what caused my problems. He offered to change my chemo regimen, and I offered to fire him. We parted ways. That was more than seven years ago. If vistonuridine had been available then, and if my severity score had been calculated in advance, I surely would have had an easier time during treatment. I am so glad that scientists are constantly improving treatments and understanding how to help patients navigate the cancer treatment experience.