Uridine Triacetate as an Antidote for Patients at Excess Risk of 5-Fluorouracil (5-FU) Toxicity Due to Overdosage or Impaired Elimination

Inclusion Criteria:

• Excess risk of toxicity due to overdosage (defined as administration of 5-FU at a dose, or infusion rate, greater than the MTD for the patient's intended regimen) of 5-FU, or impaired elimination. Impaired elimination must be documented by one of the following methods:

  • plasma 5-FU levels >10 µM more than 3 hours following cessation of 5-FU dosing
  • previous medical history from earlier 5-FU chemotherapy regimens that indicated unusual susceptibility to 5-FU toxicity, within 7-10 days of receiving 5-FU, such as Grade 3-4 diarrhea, Grade 3-4 mucositis, or Grade 4 neutropenia
  • leukocyte DPD enzyme activity <70% of that observed in the normal population (10 ± 3.4 nmol/hr)
  • presence of deleterious mutations in the DPD gene known to reflect reduced DPD activity and consequent increased risk of 5-FU toxicity
  • plasma uracil/dihydrouracil ratio greater than 2.0
• Judged by the Investigator to have the initiative and means to be compliant with the protocol
• Able to take oral medications
• Age ≥ 18 years
• Able to start treatment with uridine triacetate between 3 and 96 hours after the overdose
• Provides written informed consent (patient or legally authorized representative)

Exclusion Criteria:

• Has a known allergy to uridine triacetate or any of its excipients
• Does not have the initiative and means to be compliant with the protocol
• Unable to be compliant with taking oral medications
• More than 96 hours have elapsed since the completion of 5-FU dosing
• Unable to provide written informed consent (patient or legally authorized representative)