Effectiveness of Exogenous Albumin Administration for the Prevention of Ifosfamide‐Induced Encephalopathy

Kettle, Jacob K; Grauer, Dennis; Folker, Tanya L; O'Neal, N.K.; Henry, David W.; Williams, Casey

doi:10.1592/phco.30.8.812

Cited by 15 publications

(22 citation statements)

References 12 publications

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“…Further, low serum albumin levels are known to be associated with increased risk of severe ifosfamide-induced neurotoxicity [19]. Yet, in one study, prophylactic administration of exogenous albumin did not prevent ifosfamide-induced encephalopathy [20]. Taken together, although our study showed low albumin levels is associated with methotrexate clearance, given the unlikelihood of redistribution and amelioration of encephalopathy, we do not recommend albumin repletion to prevent delayed clearance prior to methotrexate administration.…”

Section: Discussionmentioning

confidence: 52%

Hypoalbuminemia is significantly associated with increased clearance time of high dose methotrexate in patients being treated for lymphoma or leukemia

et al. 2016

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As a weak acid, methotrexate (MTX) is bound to serum albumin and has variable protein binding. The purpose of this study was to assess serum albumin’s relationship with MTX pharmacokinetics by comparing MTX clearance and toxicities between patients with normal serum albumin to those with hypoalbuminemia. This single-center retrospective study included adult patients with leukemia or lymphoma who received their first MTX at a dose ≥ 1 gram/m2. Hypoalbuminemia was defined as serum albumin ≤ 3.4 g/dL. MTX clearance was defined as the first documented time the MTX level ≤ 0.05 micromolar. Fisher’s Exact tests and Wilcoxon Rank Sum tests were used to examine differences in toxicities and Cox proportional hazards regression was used to assess relationship with time to clearance. Of 523 patients identified, 167 patients were evaluable. One hundred thirty five patients had normal serum albumin and 32 had hypoalbuminemia. Hypoalbuminemia was associated with a higher proportion of patients experiencing edema, ascites or pleural effusions (34% vs. 12% p=0.006) and the concomitant use of nephrotoxic agents (41% vs. 20% p=0.021). Hypoalbuminemia was associated with a significantly longer time to methotrexate clearance (median: 96 hours vs 72 hour p=0.004). In addition, patients with hypoalbuminemia had a higher proportion of hyperbilirubinemia and significantly longer hospitalization (median 14 days vs. 5 days p<0.001). In conclusion, hypoalbuminemia was associated with increased time to MTX clearance and increase length of hospitalization. High dose MTX is safe to administer in patients with low albumin levels, with appropriate leucovorin rescue and good supportive care.

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Section: Discussionmentioning

confidence: 52%

Hypoalbuminemia is significantly associated with increased clearance time of high dose methotrexate in patients being treated for lymphoma or leukemia

et al. 2016

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“…The association of age with IRE was addressed in five articles ( Howell, Szabatura, Hatfield Seung, & Nesbit, 2008 ; Kettle et al, 2010 ; Lo, Shen, Chen, Dong, & Wu, 2016 ; Richards et al, 2010 ; Szabatura et al, 2015 ). There was no significant age difference between patients with and without IRE in four of these studies ( Howell et al, 2008 ; Kettle et al, 2010 ; Lo et al, 2016 ; Szabatura et al, 2015 ). Howell and colleagues (2008) completed a retrospective case-control study of 45 sarcoma patients who received ifosfamide, with and without the use of aprepitant.…”

Section: Resultsmentioning

confidence: 99%

“…The authors of all seven studies examined renal insufficiency as a risk factor for IRE. Renal insufficiency, measured by serum creatinine (SCr) in mg/dL and creatinine clearance (CrCl), was reported as a risk factor in four studies ( Kettle et al, 2010 ; Lo et al, 2016 ; Richards et al, 2010 ; Szabatura et al, 2015 ). Kettle and colleagues (2010) reported that patients with IRE had higher mean SCr, 1.05 vs. 0.85, than patients without IRE ( p = .04), although CrCl was not significantly different.…”

Section: Resultsmentioning

confidence: 99%

“…Transaminitis. The authors of four studies examined transaminitis as a risk factor for IRE ( Kettle et al, 2010 ; Lo et al, 2016 ; Richards et al, 2010 ; Sweiss et al, 2008 ). Kettle and colleagues (2010) reported that mean aspartate aminotransferase (AST) and alanine aminotransferase (ALT; units/L) were significantly higher in patients with IRE ( p < 0.01).…”

Section: Resultsmentioning

confidence: 99%

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Risk Factors for Ifosfamide-Related Encephalopathy in Adult Cancer Patients: An Integrative Review

Brink

Bowe

Dains

2020

JADPRO

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Patients receiving ifosfamide as part of their cancer treatment are at risk for ifosfamide-related encephalopathy (IRE), a potentially serious adverse event affecting up to 60% of patients. Symptoms range from transient altered mental status to coma and death. Consensus regarding risk factors for the development of IRE has not been reached in the literature. The purpose of this review is to identify risk factors for the development of IRE in adult cancer patients. A literature review was completed by searching PubMed and Scopus databases to identify articles published between 2008 and 2018. A total of 76 search results were reduced to a final sample of seven articles after applying inclusion and exclusion criteria. Published data suggest that Eastern Cooperative Oncology Group (ECOG) performance status of greater than or equal to 2, impaired renal function, hypoalbuminemia, and having multiple risk factors are risk factors for the development of IRE. Knowledge of which patients are at increased risk for the development of IRE could help clinicians to appropriately counsel patients and families regarding personal risk for the development of IRE. Clinicians may also more closely monitor patients with risk factors for IRE.

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“…To our knowledge, there are currently no studies exploring the use of single-agent thiamine versus no prophylactic agent for the prevention of IIE. 7,8 In April 2014, the University of North Carolina Medical Center (UNCMC) modified ifosfamide, carboplatin, and etoposide (ICE) chemotherapy regimens (ifosfamide 5 g/m 2 , carboplatin AUC 5, and etoposide 100 mg/m 2 ) to include thiamine 100 mg given intravenously every six hours starting on admission and continuing until discharge. This study aims to compare the incidence of IIE at UNCMC to that of Duke University Hospital (DUH), which does not routinely use prophylaxis for IIE.…”

mentioning

confidence: 99%

Evaluation of thiamine for the prevention of ifosfamide-induced encephalopathy

Lentz

Clark

Ayarza

et al. 2019

J Oncol Pharm Pract

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Study objective To determine whether thiamine prophylaxis decreases the incidence of ifosfamide-induced encephalopathy in patients receiving ifosfamide for the treatment of lymphoma. Design Retrospective, multi-center, cohort study. Patients A total of 73 patients who received 187 total cycles of ifosfamide, carboplatin, and etoposide chemotherapy for the treatment of lymphoma were included in this study. Forty-four of these patients (114 cycles) were included in the no-thiamine group and 29 (65 cycles) in the thiamine group. Measurements and main results The incidence of ifosfamide-induced encephalopathy was measured using the Common Terminology Criteria for Adverse Events and documentation in the patient chart. Regarding the primary endpoint of ifosfamide-induced encephalopathy, eight patients (18.2%) in the no-thiamine group and three patients (10.3%) in the thiamine group experienced an event ( p = 0.5087). No patient experienced more than one neurotoxic event. Conclusion There was no significant difference found in the incidence of ifosfamide-induced encephalopathy with the addition of thiamine prophylaxis in patients receiving ifosfamide, carboplatin, and etoposide–based chemotherapy regimens for lymphoma. Larger, prospective studies assessing the use of thiamine prophylaxis in this patient population are warranted to better assess its impact on the incidence of ifosfamide-induced encephalopathy.

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Effectiveness of Exogenous Albumin Administration for the Prevention of Ifosfamide‐Induced Encephalopathy

Abstract: Prophylactic therapy with exogenous albumin is not an effective strategy for the prevention of IIE. The novel risk-stratification model appears to be an effective method for predicting patients with the greatest potential for developing this adverse effect.

Cited by 15 publications

References 12 publications

Hypoalbuminemia is significantly associated with increased clearance time of high dose methotrexate in patients being treated for lymphoma or leukemia

Hypoalbuminemia is significantly associated with increased clearance time of high dose methotrexate in patients being treated for lymphoma or leukemia

Risk Factors for Ifosfamide-Related Encephalopathy in Adult Cancer Patients: An Integrative Review

Evaluation of thiamine for the prevention of ifosfamide-induced encephalopathy

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