Vistogard effectively treats 5-FU chemotherapy toxicity

Issue: February 25, 2016

SAN FRANCISCO — Vistogard is a safe and effective life-saving antidote for cancer patients who overdosed on 5-fluorouracil or capecitabine or exhibited early-onset, severe or life-threatening toxicity, according to a poster presented at the Gastrointestinal Cancers Symposium.

Vistogard (uridine triacetate, BTG/Wellstat Therapeutics) is an orally bioavailable prodrug of uridine, a pyrimidine analog that was recently approved by the FDA for emergency treatment of adults and children who experience 5-fluorouracil (5-FU) or capecitabine overdose or toxicity.

“The chemotherapy fluorouracil is used very commonly, so the side effects typically are very well managed, but we do have situations where patients get early-onset severe toxicity from fluorouracil or capecitabine treatment,” Wen Wee Ma, MD, associate professor of oncology, GI Cancers & Drug Development Program, Roswell Park Cancer Institute, told Healio Gastroenterology. “Situations like that historically have been very difficult to treat, and most patients end up passing away” — about 1,300 patients per year, he said. “So there’s a real need to come up with a good management or antidote for that.”

Ma and colleagues administered 10 g uridine triacetate every 6 hours for a total of 20 doses beginning as soon as possible (range, 7-96 hours after chemotherapy) in patients with 5-FU or capecitabine overdose (n = 111) or severe rapid-onset toxicities (n = 24). Survival compared with historical controls (n = 47), time to resumed chemotherapy and safety served as clinical endpoints. The majority of patients had colorectal cancer (56.2%), and the majority of toxicities were hematological and GI (54.4%).

Almost all patients (96%) fully recovered within 30 days of treatment, with cardiotoxicity and neurotoxicity being rapidly reversed. No patients treated within 96 hours died; in comparison, 81% of historical controls who received standard supportive care died.

Moreover, 37.7% of those who overdosed were able to resume chemotherapy within 30 days (median, 20 days after 5-FU). Mild to moderate adverse events attributed to treatment included vomiting (10%), nausea (5%) and diarrhea (5%).

“If medical oncologists or health care providers come across patients with toxicity that is … more severe than expected or early-onset, uridine triacetate should definitely be used,” Ma said. “The study [also] shows that if it is administered within 96 hours you’ll have the best benefit, so I think that’s one thing we need to raise awareness [about].” – by Adam Leitenberger

Reference:

Ma W, et al. Abstract 655. Presented at: Gastrointestinal Cancers Symposium; Jan. 21-23, 2016; San Francisco.

Disclosure: Ma reports he is on the advisory board for Wellstat. Please see the abstract for a list of all other researchers’ relevant financial disclosures.