NEW YORK (Reuters Health) – In cancer patients accidentally overexposed with 5-fluorouracil (5-FU) chemotherapy, the investigational drug vistonuridine (Wellstat Therapeutics Corp) may be lifesaving, according to research to be reported June 1 at the American Society of Clinical Oncology’s annual meeting in Orlando.

Uridine is a direct biochemical antagonist of 5-FU toxicity. Vistonuridine is an orally administered prodrug of uridine that delivers approximately eight times more uridine than administration of uridine itself.

The presentation at ASCO will report on 17 patients overdosed with 5-FU who received vistonuridine within 8 to 96 hours of overexposure. The drug was supplied under the US Food and Drug Administration’s emergency-use Investigational New Drug provisions.

In a pre-meeting interview with Reuters Health, Michael Bamat, Wellstat’s vice president for research and development, noted that all 17 of the vistonuridine-treated patients recovered fully. Without the antidote, at least 13 of these patients would have died based on the dose and rate of 5-FU administration.

“Vistonuridine performed very well and it also is, in itself, a very safe drug,” Bamat said.

The National Institutes of Health estimates that 250,000 patients in the United States undergo 5-FU therapy annually and that 1,300 die from toxicities associated with 5-FU and another 8,000 have serious 5-FU-related toxicities.

5-FU overexposure can result from infusion pump malfunction or misprogramming, dose calculation errors, excess or accidental ingestion of oral 5-FU sources, such as capecitabine or tegafur, or concomitant drugs that impair 5-FU degradation.

There is currently no approved antidote for 5-FU overexposure; current treatments are largely palliative — GCSF or GM-CSF to get the white blood cell count back up, antiemetics, hydration, and antibiotics if infection develops. “There really isn’t much to do in these cases,” Bamat said.

“Because no antidote for 5-FU overexposure is approved today, we have been responding to emergency requests for vistonuridine,” Bamat said.

Vistonuridine was granted orphan drug status by the US FDA on May 1 and Wellstat is anticipating orphan drug status in Europe. The company plans to seek regulatory approval in the US and Europe.