Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity
| Autor: | Michael K. Bamat, Thomas R. King, Thomas H. Cartwright, Bassel F. El-Rayes, Reid von Borstel, Wen Wee Ma, Marwan Fakih, James Posey, Muhammad Wasif Saif |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Chemotherapy medicine.medical_specialty business.industry Nausea medicine.medical_treatment Uridine Triacetate medicine.disease Capecitabine 03 medical and health sciences Dihydropyrimidine dehydrogenase deficiency 030104 developmental biology 0302 clinical medicine Oncology Fluorouracil 030220 oncology & carcinogenesis Internal medicine Anesthesia medicine Vomiting Mucositis medicine.symptom business medicine.drug |
| Zdroj: | Cancer. 123:345-356 |
| ISSN: | 0008-543X |
| Popis: | BACKGROUND Increased susceptibility to 5-fluorouracil (5-FU)/capecitabine can lead to rapidly occurring toxicity caused by impaired clearance, dihydropyrimidine dehydrogenase deficiency, and other genetic variations in the enzymes that metabolize 5-FU. Life-threatening 5-FU overdoses occur because of infusion pump errors, dosage miscalculations, and accidental or suicidal ingestion of capecitabine. Uridine triacetate (Vistogard) was approved in 2015 for adult and pediatric patients who exhibit early-onset severe or life-threatening 5-FU/capecitabine toxicities or present with an overdose. Uridine triacetate delivers high concentrations of uridine, which competes with toxic 5-FU metabolites. METHODS In 2 open-label clinical studies, patients who presented with a 5-FU/capecitabine overdose or an early onset of severe toxicities were treated. Patients received uridine triacetate as soon as possible (most within the first 96 hours after 5-FU/capecitabine). Outcomes included survival, resumption of chemotherapy, and safety. Their survival was compared with the survival of a historical cohort of overdose patients who received only supportive care. RESULTS A total of 137 of 142 overdose patients (96%) treated with uridine triacetate survived and had a rapid reversal of severe acute cardiotoxicity and neurotoxicity; in addition, mucositis and leukopenia were prevented, or the patients recovered from them. In the historical cohort, 21 of 25 patients (84%) died. Among the 141 uridine triacetate–treated overdose patients with a diagnosis of cancer (the noncancer patients included 6 intentional or accidental pediatric overdoses), 53 resumed chemotherapy in |
| Databáze: | OpenAIRE |
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