TY - JOUR
T1 - FDA approval
T2 - Uridine triacetate for the treatment of patients following fluorouracil or capecitabine overdose or exhibiting early-onset severe toxicities following administration of these drugs
AU - Ison, Gwynn
AU - Beaver, Julia A.
AU - McGuinn, W. David
AU - Palmby, Todd R.
AU - Dinin, Jeannette
AU - Charlab, Rosane
AU - Marathe, Anshu
AU - Jin, Runyan
AU - Liu, Qi
AU - Hong Chen, Xiao
AU - Ysern, Xavier
AU - Stephens, Olen
AU - Bai, Ge
AU - Wang, Yaning
AU - Dorff, Sarah E.
AU - Cheng, Joyce
AU - Tang, Shenghui
AU - Sridhara, Rajeshwari
AU - Pierce, William
AU - McKee, Amy E.
AU - Ibrahim, Amna
AU - Kim, Geoffrey
AU - Pazdur, Richard
N1 - Publisher Copyright:
© 2016 AACR.
PY - 2016/9/15
Y1 - 2016/9/15
N2 - On December 11, 2015, the FDA approved uridine triacetate (VISTOGARD; Wellstat Therapeutics Corporation) for the emergency treatment of adult and pediatric patients following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, and of those who exhibit early-onset, severe, or lifethreatening toxicity affecting the cardiac or central nervous system, and/or early onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration. Uridine triacetate is not recommended for the nonemergent treatment of adverse reactions associated with fluorouracil or capecitabine because it may diminish the efficacy of these drugs, and the safety and efficacy of uridine triacetate initiated more than 96 hours following the end of administration of these drugs has not been established. The approval is based on data from two single-arm, open-label, expanded-access trials in 135 patients receiving uridine triacetate (10 g or 6.2 g/m2 orally every 6 hours for 20 doses) for fluorouracil or capecitabine overdose, or who exhibited severe or life-threatening toxicities within 96 hours following the end of fluorouracil or capecitabine administration. Ninety-six percent of patients met the major efficacy outcome measure, which was survival at 30 days or survival until the resumption of chemotherapy, if prior to 30 days. The most common adverse reactions were vomiting, nausea, and diarrhea. This article summarizes the FDA review of this New Drug Application, the data supporting approval of uridine triacetate, and the unique regulatory situations encountered by this approval. Clin Cancer Res; 22(18); 4545-9.
AB - On December 11, 2015, the FDA approved uridine triacetate (VISTOGARD; Wellstat Therapeutics Corporation) for the emergency treatment of adult and pediatric patients following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, and of those who exhibit early-onset, severe, or lifethreatening toxicity affecting the cardiac or central nervous system, and/or early onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration. Uridine triacetate is not recommended for the nonemergent treatment of adverse reactions associated with fluorouracil or capecitabine because it may diminish the efficacy of these drugs, and the safety and efficacy of uridine triacetate initiated more than 96 hours following the end of administration of these drugs has not been established. The approval is based on data from two single-arm, open-label, expanded-access trials in 135 patients receiving uridine triacetate (10 g or 6.2 g/m2 orally every 6 hours for 20 doses) for fluorouracil or capecitabine overdose, or who exhibited severe or life-threatening toxicities within 96 hours following the end of fluorouracil or capecitabine administration. Ninety-six percent of patients met the major efficacy outcome measure, which was survival at 30 days or survival until the resumption of chemotherapy, if prior to 30 days. The most common adverse reactions were vomiting, nausea, and diarrhea. This article summarizes the FDA review of this New Drug Application, the data supporting approval of uridine triacetate, and the unique regulatory situations encountered by this approval. Clin Cancer Res; 22(18); 4545-9.
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U2 - 10.1158/1078-0432.CCR-16-0638
DO - 10.1158/1078-0432.CCR-16-0638
M3 - Article
C2 - 27401247
AN - SCOPUS:84990057232
SN - 1078-0432
VL - 22
SP - 4545
EP - 4549
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -