Neurological Toxicity of Ifosfamide

Nicolao, P.; Giometto, Bruno

doi:10.1159/000073352

Cited by 84 publications

(66 citation statements)

References 32 publications

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“…The mechanism of neurologic toxicity of ifosfamide remains unknown. Symptoms have been reported in 5–30% of all patients treated with ifosfamide [24]. Ifosfamide-induced encephalopathy can be precipitated by risk factors such as low albumin, poor performance status prior to treatment, renal failure, hepatic insufficiency, female sex with bulky disease, disease confined to the pelvis, and advanced age [24,25].…”

Section: Discussionmentioning

confidence: 99%

High-Dose Ifosfamide as Second- or Third-Line Chemotherapy in Refractory Bone and Soft Tissue Sarcoma Patients

et al. 2011

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Introduction: For patients with refractory bone and soft tissue sarcoma (STS), treatment options have been limited. Ifosfamide is an alkylating agent with well-demonstrated efficacy against STS, and dose-dependent activity. The aim of this retrospective study was to evaluate the response rate, progression-free survival (PFS), progression-free rate (PFR), and median duration of response to high-dose ifosfamide (HDI) as at least second-line chemotherapy for patients with advanced bone sarcoma and STS. Patients and Methods: Thirty metastatic, unresectable sarcoma patients who were treated with HDI chemotherapy between May 1999 and November 2007 were included in the analysis. In total, 106 cycles (median 3 cycles; range 1–8 cycles) were administered. Twenty-one patients received treatment as second-line chemotherapy, and 9 patients as third-line treatment. HDI was given at a dose of 2 g/m² over 3 h, and at a dose of 2 g/m² per day; continuous infusion was administered on 6 consecutive days (2 g/m²/6 days) every 3 weeks. Results: After a median follow-up of 49 months (range 10–114), median PFS was 2.9 months (range 0.4–9.3) and median overall survival 8.7 months (range 0.4–57.8). The 3- and 6-month PFR were 47% (SE 9.1%) and 20% (SE 7.3%), respectively. Median response duration of HDI was 2.9 months (range 0.7–7.6). Of the 28 evaluable patients, 2 (7%) achieved complete response, 5 (18%) partial response, and 4 (14%) stable disease, and overall disease control was 39%. Two responders out of 7 (28.5%) and 4 patients out of 11 (36%) with controlled disease by HDI had a synovial sarcoma. Two patients were not evaluable because they were switched to another treatment due to ifosfamide-induced encephalopathy. Grade 3–4 neutropenia was seen in 13 (43%) patients, and treatment-related death was observed in one patient. Conclusion: HDI at a total dose of 14 g/m² with mesna is still an active salvage regimen, particularly in patients with synovial sarcomas.

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Section: Discussionmentioning

confidence: 99%

High-Dose Ifosfamide as Second- or Third-Line Chemotherapy in Refractory Bone and Soft Tissue Sarcoma Patients

et al. 2011

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“…Erbulozole and doxifluridine is known to cause WE-like encephalopathy [28, 41]. Ifosfamide is also associated with encephalopathy syndrome that is usually reversible [42]. Thiamine might be beneficial in reversing ifosfamide encephalopathy [43].…”

Section: Discussionmentioning

confidence: 99%

Wernicke’s Encephalopathy: An Underrecognized and Reversible Cause of Confusional State in Cancer Patients

Kuo

Debnam²,

Fuller³

et al. 2008

Oncology

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Background: Wernicke’s encephalopathy (WE) is a neurological emergency which presents with symptoms of confusion, ophthalmoplegia, and ataxia. Cancer patients are at high risk of this acute encephalopathy due to chronic malnutrition, chemotherapy-induced nausea and vomiting, and consumption of thiamine by rapidly growing tumors. A high index of suspicion is important as these critically ill patients may not present with the classic triad of symptoms. Methods: This study is a retrospective review of 5 patients with WE identified at M.D. Anderson Cancer Center, Houston, Tex., USA. Detailed clinical histories, risk factors, imaging, and histopathological characteristics are described. Results: Five WE patients were identified and all patients had rapidly growing cancers and were undergoing active treatment. All patients had poor nutritional status due to chronic nausea from chemotherapy. Three patients received bone marrow transplantation (BMT). Acute confusion was the most common symptom. Magnetic resonance imaging studies of the brain revealed restricted diffusion and fluid attenuation inversion recovery sequence hyperintensity in the medial thalami and periaqueductal gray matter. In 2 cases, WE was considered antemortem, and only 1 was empirically treated with thiamine, which rapidly reversed the imaging findings within 7 days and led to clinical improvement. Other cases were diagnosed at autopsy. Conclusion: It is crucial to consider WE in the differential diagnosis for all cancer patients with confusion. Cancer patients with malnutrition and patients with BMT are at high risk of developing WE. To prevent this devastating and often fatal neurologic complication, all cancer patients with confusion should be empirically treated with thiamine.

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“…Ifosfamide-induced encephalopathy can be precipitated by risk factors such as low serum albumin, poor performance status, any degree of renal dysfunction, and age (children are more susceptible than adults) [56]. It is manifested by visual and auditory hallucinations, logorrhea, mental confusion, agitation, seizures, coma, and occasionally death.…”

Section: Side Effects Of Ifosfamidementioning

confidence: 99%

The Pharmacologic Basis of Ifosfamide Use in Adult Patients with Advanced Soft Tissue Sarcomas

et al. 2007

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After completing this course, the reader will be able to:1. Describe the current role of ifosfamide in the treatment of soft tissue sarcomas in adult patients.2. Discuss factors that may affect ifosfamide metabolism and its therapeutic index.3. Explain the advantages of ifosfamide over doxorubicin in the context of new treatment combinations.4. Discuss strategies to improve survival outcome in patients with soft tissue sarcoma.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTThe treatment outcome of patients with locally advanced and metastatic soft tissue sarcomas is poor. Doxorubicin is regarded as standard treatment, but its use is featured by the occurrence of cardiotoxicity. This hinders the administration of this drug at high doses or in combination with, in theory, attractive newly developed targeted drugs, such as vascular endothelial growth factor (VEGF) pathway inhibitors. The combination of doxorubicin and VEGF pathway inhibitors has been shown to yield an unacceptable high rate of cardiomyopathy. Ifosfamide is the only drug that consistently shows response rates comparable to those of doxorubicin. The lack of cardiotoxicity renders this drug a much more attractive alternative than doxorubicin to be explored at high doses or as part of new drug combinations. This review addresses the clinical pharmacology, metabolism, and present role of ifosfamide in the treatment of locally advanced and/or metastatic soft tissue sarcomas, excluding gastrointestinal stromal tumors, the Ewing-like sarcomas, and other small blue round cell tumors. Furthermore, this review focuses on the anticipated growing role of ifosfamide in the development of new treatment strategies. The Oncologist 2007;

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Neurological Toxicity of Ifosfamide

Cited by 84 publications

References 32 publications

High-Dose Ifosfamide as Second- or Third-Line Chemotherapy in Refractory Bone and Soft Tissue Sarcoma Patients

High-Dose Ifosfamide as Second- or Third-Line Chemotherapy in Refractory Bone and Soft Tissue Sarcoma Patients

Wernicke’s Encephalopathy: An Underrecognized and Reversible Cause of Confusional State in Cancer Patients

The Pharmacologic Basis of Ifosfamide Use in Adult Patients with Advanced Soft Tissue Sarcomas

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