5-Fluorouracil Neurotoxicity in the Absence of Dihydropyrimidine Dehydrogenase Deficiency Case Report

Jules, Rebecca; Thaper, Arushi; Foster, Ryan; Ameli, Pouya; Robinson, Christopher; Pizzi, Michael; Babi, Marc-Alain; Maciel, Carolina B.; Busl, Katharina M.; Reddy, Raju; Roth, William

doi:10.1177/19418744211068913

Cited by 4 publications

(3 citation statements)

References 9 publications

(12 reference statements)

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“…Despite this association, studies have not shown a significant clinical correlation to necessitate pretreatment screening [ 6 ]. This is confirmed by case reports of patients who have developed 5-FU-associated neurotoxicity in the absence of DPD deficiency, as was seen in our patient [ 7 ]. The clinical signs of acute cerebellar syndrome secondary to 5-FU toxicity, which included ataxia, dysarthria, dysmetria, and nystagmus, were first characterized by Riehl and Brown [ 8 ].…”

Section: Introductionsupporting

confidence: 92%

5-Fluorouracil Neurotoxicity in a Patient With Normal Dihydropyrimidine Dehydrogenase Activity

Natarajan,

Onyechi,

Ohemeng-Dapaah

2023

Cureus

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5-fluorouracil (5-FU) is a well-known chemotherapeutic agent used for the treatment of colon cancer and other solid malignancies. Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catalyzes 5-FU, and if a patient is deficient, such as through a gene mutation, they can be predisposed to severe toxicity. Although 5-FU-induced neurotoxicity is extremely rare, it can be fatal. We report a case of 5-FU neurotoxicity in a 56-year-old male patient with keratinizing squamous cell carcinoma of the anal canal on concurrent chemoradiation therapy consisting of 5-FU, mitomycin, and radiotherapy. Encephalopathy, dysarthria, and ataxia were noted on day three of treatment. MRI of the brain showed a pattern of global anoxic brain injury. DPD testing was negative for polymorphism, and the patient’s symptoms improved after treatment with uridine triacetate, the treatment for 5-FU toxicity.

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Section: Introductionsupporting

confidence: 92%

5-Fluorouracil Neurotoxicity in a Patient With Normal Dihydropyrimidine Dehydrogenase Activity

Natarajan,

Onyechi,

Ohemeng-Dapaah

2023

Cureus

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“…Several clinical signs of 5-FU neurotoxicity have been described, such as headache, dysarthria, cerebellar syndrome, oculomotor disorders, confusion, cognitive disorders, Parkinson's syndrome, seizure, and coma [5] , [6] , [7] . Diagnosis of TL is based on a number of arguments, including the onset of symptoms after taking 5-FU, and the exclusion of other etiologies that may explain the neurological signs [8] .…”

Section: Discussionmentioning

confidence: 99%

5-Fluorouracil-induced acute leukoencephalopathy: Case report and literature review

Ziani,

Nasri,

Kamaoui

et al. 2024

Radiology Case Reports

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“… 3 5-FU, the uracil nucleotide analog, is one of the cytotoxic medications used in various types of cancers such as stomach, colorectal, and pancreatic cancers in addition to cervical and breast cancer. 4 The toxicities of 5-FU appear in several organs such as the kidney, 5 , 6 liver, 7 CNS, 8 and the heart. 9 Many mechanisms have been proposed for the nephrotoxic effect of 5-FU; DNA damage and nontargeting apoptotic cell death via increasing caspase-3 activity in the kidneys are the most deleterious effect of 5-FU.…”

Section: Introductionmentioning

confidence: 99%

Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats

Ali¹,

Ahmed²,

Aziz³

2022

JIR

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The present study was designed to evaluate the possible synergistic effects of telmisartan and quercetin in 5 fluorouracil (5-FU) induced nephrotoxicity in rats. Methodology: Forty male rats were randomly divided into five groups: The negative control group, the positive control group that received 5-FU, the telmisartan group, receiving 10 mg/kg, the quercetin group, receiving 80 mg/kg, and the combination of telmisartan and quercetin group. All the treatments were given orally for 14 days. A single intraperitoneal injection of 5-FU (150 mg/kg) on day 13 of the experiment was given except for the negative control group. On the 15th day after scarification, approximately 5 mL of blood was collected and used for measurement of CBC, urea, creatinine, and uric acid. The kidneys were used for histopathological examination and for the measurement of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), Cystatin C (Cys-C), and total antioxidant capacity (TAOC). Results: The combination therapy significantly attenuated the levels of tissue KIM-1, NGAL, Cys-C, and serum uric acid as well as blood inflammatory markers, Neutrophil/Lymphocyte (NLR), Monocyte/Lymphocyte (MLR), and Platelets/Lymphocyte ratios (PLR), and restored the TAOC. The histopathological findings greatly support the biochemical tests. Conclusion:The results strongly suggest the renoprotective effects of telmisartan and quercetin in combination against the nephrotoxic effect of 5-FU through decreasing the levels of KIM-1, NGAL, and cys-C, and the novel inflammatory markers of kidney injury like NLP, MLR, and PLR, as well as decreasing uric acid and restoring the TAOC. The proposed mechanism could be the additive inhibitory effect on RAS provided by both telmisartan and quercetin.

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5-Fluorouracil Neurotoxicity in the Absence of Dihydropyrimidine Dehydrogenase Deficiency Case Report

Cited by 4 publications

References 9 publications

5-Fluorouracil Neurotoxicity in a Patient With Normal Dihydropyrimidine Dehydrogenase Activity

5-Fluorouracil Neurotoxicity in a Patient With Normal Dihydropyrimidine Dehydrogenase Activity

5-Fluorouracil-induced acute leukoencephalopathy: Case report and literature review

Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats

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