Ifosfamide extrapyramidal neurotoxicity

Anderson, Norwood; Tandon, Deepak S.

doi:10.1002/1097-0142(19910701)68:1<72::aid-cncr2820680114>3.0.co;2-#

Cited by 43 publications

(13 citation statements)

References 15 publications

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“…Prompt cessation of ifosfamide at the earliest signs of encephalopathy is essential. 19,20 Methylene blue, thiamine, and intra venous albumin (for those with low serum albumin levels) have been shown to improve recovery in patients with grade 3 or 4 ifosfamide-induced encephalopathy. 18 Modifications to manage acute reversible effects For testicular cancer patients undergoing chemotherapy with curative intent, dose reduction or substitution of cisplatin with carboplatin should be avoided as decreased dose intensity of cisplatin compromises cure rates.…”

Section: Reviewsmentioning

confidence: 99%

Complications associated with chemotherapy in testicular cancer management

Fung

Vaughn

2011

Nat Rev Urol

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Testicular cancer is the most common solid tumor among men aged 15-35 years. The introduction of cisplatin-based chemotherapy has resulted in a cure rate of over 95% for men with testicular cancer, which has put increased emphasis on understanding the morbidity associated with chemotherapy. Hematological, gastrointestinal, gonadal, otological, renal, neurological, and pulmonary toxicities are the most common acute adverse effects. Although most patients recover, some of these effects can persist after the chemotherapy regimen has been completed and can become chronic problems. The late complications associated with cisplatin-based chemotherapy include secondary malignancies, cardiovascular disease, avascular necrosis, and cognitive impairment. Late complications can have considerable effects on survival and quality of life, so close monitoring of patients is critical for the early diagnosis of late adverse effects and to limit associated damage. All patients should adopt a healthy lifestyle and follow age-appropriate cancer screening programs. Hormonal supplementation should be considered for those with a low testosterone level, in order to reduce the risk of sexual dysfunction and metabolic syndrome. Prompt diagnosis of avascular necrosis is essential, and it should be considered in the differential diagnosis for any long-term testicular cancer survivor complaining of hip pain. Finally, sperm cryopreservation should be discussed with all patients before chemotherapy is initiated.

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Section: Reviewsmentioning

confidence: 99%

Complications associated with chemotherapy in testicular cancer management

Fung

Vaughn

2011

Nat Rev Urol

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“…The study was therefore terminated prematurely. Other reports have also highlighted this type of toxicity; somnolence is most common, although features such as forgetfulness, nightmares, seizures, tonic clonic spasms, asterixis and extrapyramidal symptoms may occur [11][12][13][14][15]. With severe and progressive encephalopathy, logorrhoea, palilalia, perseveration of writing and speech, and marked disorientation appear after 20 to 50 hours, following which patients may enter a trance, and coma soon follows.…”

Section: Discussionmentioning

confidence: 99%

The Neurotoxicity and Pharmacokinetics of Oral Ifosfamide

et al. 2015

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Purpose: Ifosfamide can cause an unexplained encephalopathy. The incidence after intravenous infusion is 10%, but is much higher after oral administration. This study assesses the pharmacokinetics of oral ifosfamide in relation to neurotoxicity. Patients and Methods:Eleven patients received oral ifosfamide 500 mg twice daily for 14 days, with concurrent oral mesna. The concentrations of ifosfamide, isophosphoramide mustard, 2-dechloroethylifosfamide, 3dechloroethylifosfamide, carboxyifosfamide, ketoifosfamide, chloroethylamine and 3-oxazolidine-2-one were measured using GC-MS. Patients were evaluated clinically, and also with the EEG, psychometric testing, the national adult reading test, and the mini-mental state examination.Results: A decrease in the electroencephalogram alpha frequency was observed, with the development of pathological slow wave activity. Psychometric performance was also impaired. Neurotoxicity was progressive during treatment, and the incidence of grade 3 neurotoxicity was 22%. The mean day 14 / day 1 Cmax ratios for 2-dechloroethylifosfamide and 3-dechloroethylifosfamide were 2.73 (± 2.11) and 2.04 (± 1.32) respectively. The metabolite with the lowest ratio was isophosphoramide mustard 1.07 (± 0.39). High chloroethylamine Cmax values were associated with lower alpha frequencies, and increased clinical neurotoxicity. Conclusion:Oral ifosfamide 500 mg twice daily for 14 days causes unacceptable neurotoxicity. It was not possible to identify one particular metabolite responsible for the neurotoxicity, although the dechloroethyl metabolites and chloroethylamine are implicated.

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“…Nevertheless, this drug has been used without excessive neurotoxicity in some cases 7. Some other rare manifestations have also been described, such as extrapyramidal syndrome 8.…”

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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Ifosfamide extrapyramidal neurotoxicity

Cited by 43 publications

References 15 publications

Complications associated with chemotherapy in testicular cancer management

Complications associated with chemotherapy in testicular cancer management

The Neurotoxicity and Pharmacokinetics of Oral Ifosfamide

Ifosfamide neurotoxicity: An atypical presentation with psychiatric manifestations

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