Fatal Encephalopathy with Ifosfamide/Mesna

Amparo, Verdeguer; Castel, Victoria; Esquembre, Carlos; Ferrís, J; Fernández, José Marı́a; Ruiz, Jose G.

doi:10.3109/08880018909034311

Cited by 19 publications

(9 citation statements)

References 8 publications

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“…The prognosis of ifosfamide neurotoxicity is favorable, as the adverse complications resolve after stopping treatment in the great majority of cases. Even in severely affected cases with coma 9, the symptoms are usually transient and spontaneously reversible with no apparent sequelae 10,11, although several fatal cases have been described 6,12,13; the fatalities have sometimes occurred after continuation of treatment despite the presence of a transient neurologic episode. However, neurological symptoms may sometimes recur with resumption of treatment 2,14.…”

Section: Discussionmentioning

confidence: 99%

Ifosfamide neurotoxicity: An atypical presentation with psychiatric manifestations

Kerdudo

Orbach

Sarradet³

et al. 2005

Pediatric Blood & Cancer

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Ifosfamide can be responsible for acute central neurotoxicity in children and adolescents treated for cancer. The signs of acute encephalopathy most frequently observed are: alteration of consciousness, cerebellar syndrome, asthenia, urinary incontinence, cranial nerve palsy, and seizures. Various combinations of these signs may occur, but disorders of consciousness and drowsiness are common. We describe the case of a young man presenting with reversible acute hypomanic disorder during ifosfamide-based chemotherapy and discuss the possible mechanisms of this toxicity.

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Section: Discussionmentioning

confidence: 99%

Ifosfamide neurotoxicity: An atypical presentation with psychiatric manifestations

Kerdudo

Orbach

Sarradet³

et al. 2005

Pediatric Blood & Cancer

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“…[1][2][3] Symptoms of ifosfamide-induced encephalopathy include conf usion, disorientation, restlessness, hallucinations, somnolence, a phasia, lethargy and seizures. 7 The estimated i ncidence of ifosfamide-induced encephalopathy varies from 10% to 40% in the literature. [4][5][6] A lthough toxicity is most often reversible, cases of complications that may lead to coma or death have been reported.…”

Section: What Is K Nown and Objec Tivementioning

confidence: 99%

“…[4][5][6] A lthough toxicity is most often reversible, cases of complications that may lead to coma or death have been reported. 7 The estimated i ncidence of ifosfamide-induced encephalopathy varies from 10% to 40% in the literature. 4,[8][9][10] However, these studies cover a wide r ange of populations and are not very comparable.…”

Section: What Is K Nown and Objec Tivementioning

confidence: 99%

Ifosfamide‐induced encephalopathy: Brand‐name (HOLOXAN®) vs generic formulation (IFOSFAMIDE EG®)

et al. 2019

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Summary What is known and Objective Two forms of ifosfamide are commercially available in France: HOLOXAN® (brand‐name drug) and IFOSFAMIDE EG® (generic drug). Following the marketing launch of the generic drug, there has been a significant increase in cases of ifosfamide‐induced encephalopathy reported in France. Our objective is to compare the incidence of ifosfamide‐induced encephalopathy in adult patients treated with HOLOXAN® or IFOSFAMIDE EG®. Methods This is a retrospective study of adult patients treated with ifosfamide in two medical centers from 2013 to 2017, with data analysed from medical records. Comparisons of patients were made, according to the formulation used and according to the occurrence of ifosfamide‐induced encephalopathy. The groups of patients were compared using a chi‐square or Fisher's exact test for qualitative parameters and a Wilcoxon test for quantitative parameters. To include confounding factors in the analysis of the impact of drug formulation on the occurrence of ifosfamide‐induced encephalopathy, a generalized linear model was performed with the occurrence of ifosfamide‐induced encephalopathy as the dependent parameter, and the formulation and the confounding factors as explanatory parameters. Results and Discussion A total of 191 patients were included: 103 patients received HOLOXAN® (53.9%) and 88 patients received IFOSFAMIDE EG® (46.1%). In the HOLOXAN® group, the median infusion time was higher (12 hours vs 3h, P < 0.001) and aprepitant was administered more frequently (78.6% vs 69.7%, P < 0.001) than for the IFOSFAMIDE EG® group. Ifosfamide‐induced encephalopathy occurred in 11 patients (5.8%, CI 95% [2.9%, 10.0%]). In the ifosfamide‐induced encephalopathy group, median infusion time was higher (12 hours [12; 24] vs 3 hours [2; 12] P < 0.001) and a poor performance status was more frequent (54.5% vs 13.9%, P = 0.002) than in the group without ifosfamide‐induced encephalopathy. The frequency of ifosfamide‐induced encephalopathy in the HOLOXAN® group was 1.9% (2/103) against 10.2% (9/88) in the IFOSFAMIDE EG® group (P = 0.014). Multivariate analysis revealed that treatment with IFOSFAMIDE EG® resulted in significantly more ifosfamide‐induced encephalopathies compared to HOLOXAN® (OR and CI 95%:7.4 [1.4; 39.5], P = 0.018). We identified two other risk factors for ifosfamide‐induced encephalopathy: long‐term infusion and a performance status of two or higher. What is New and Conclusion The formation of chloroethylamine in solution could be the cause of more frequent ifosfamide‐induced encephalopathies with IFOSFAMIDE EG® compared to HOLOXAN®. Application of these data could help in the choice of ifosfamide formulation in adult patients to decrease the risk of ifosfamide‐induced encephalopathy, and more specifically for patients with risk factors.

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“…However, the long-term consequences of ifosfamide neuropsychiatric toxicity are not known [2]. Fatal cases have been described in the literature, with some of them occurring with continuation of treatment despite the presence of transient neurological symptoms [16]. Some groups use a combination of methylene blue, 5% glucose, and thiamine during ifosfamide chemotherapy to prevent recurrence of neuropsychiatric toxicity [17].…”

Section: Prophylaxismentioning

confidence: 99%

Ifosfamide neuropsychiatric toxicity in patients with cancer

Alici-Evcimen

Breitbart

2007

Psycho-Oncology

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Ifosfamide is a chemotherapy agent commonly used in the treatment of several solid tumors and hematologic malignancies. Common ifosfamide toxicities are bone marrow suppression, alopecia, nausea and vomiting. Less common, but striking, are the rare but dramatic neuropsychiatric toxicities with discrete neurological symptoms and delirium. We report here a case of ifosfamide neuropsychiatric toxicity which presented with an isolated psychotic disorder with delusions, and was successfully treated with methylene blue. Current literature on treatment and prophylaxis of this clinically challenging chemotherapy-induced complication is presented.

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Fatal Encephalopathy with Ifosfamide/Mesna

Cited by 19 publications

References 8 publications

Ifosfamide neurotoxicity: An atypical presentation with psychiatric manifestations

Ifosfamide neurotoxicity: An atypical presentation with psychiatric manifestations

Ifosfamide‐induced encephalopathy: Brand‐name (HOLOXAN®) vs generic formulation (IFOSFAMIDE EG®)

Ifosfamide neuropsychiatric toxicity in patients with cancer

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