Evaluating risk factors for the development of ifosfamide encephalopathy

Am J Clin Oncol. 2005 Jun;28(3):277-80. doi: 10.1097/01.coc.0000158439.02724.5a.


Background: Ifosfamide is an important part of chemotherapeutic regimens used to treat a variety of malignancies. One potential side effect of the drug is encephalopathy, which may manifest itself as a variety of symptoms, ranging from agitation to seizures and coma. The goal of this review is to identify the prevalence of ifosfamide encephalopathy at Barnes-Jewish Hospital from 1995 to 2003, and to identify risk factors associated with the condition.

Methods: A retrospective cohort study of all patients receiving ifosfamide at Barnes-Jewish Hospital in St. Louis, Missouri, from late 1995 to early 2003 was performed. In sum, the authors reviewed chemotherapy administrations for a total of 237 individual patients. Patients were divided into control subjects and cases of encephalopathy.

Results: A total of 237 patients received ifosfamide during the study period. Thirty-eight patients (16%) underwent chemotherapy rounds during which encephalopathy occurred. Serum albumin was significantly lower in the case population (3.3 g/dL) compared with the control population (3.7 g/dL). The odds ratio of hypoalbuminemia for the development of encephalopathy was calculated as 4.3 (CI, 2.26-8.3). The average creatinine values were in the normal range for both groups, although slightly higher in the case population with statistical significance. Age and ifosfamide dose were not significantly different between the 2 groups. The most common manifestation of encephalopathy was confusion. Methylene blue, which has been thought to reverse the condition, was administered in 26 cases.

Conclusion: The prevalence of ifosfamide encephalopathy during the study period was 16%. Albumin was significantly lower among those patients who experienced encephalopathy, whereas age, creatinine, and ifosfamide dose were not significantly different between the 2 groups.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • Akathisia, Drug-Induced / etiology
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Brain Diseases / chemically induced*
  • Brain Diseases / drug therapy
  • Brain Diseases / epidemiology
  • Cohort Studies
  • Confusion / chemically induced
  • Confusion / drug therapy
  • Confusion / epidemiology
  • Creatinine / blood
  • Female
  • Hallucinations / chemically induced
  • Hallucinations / epidemiology
  • Humans
  • Hypoalbuminemia / epidemiology
  • Ifosfamide / adverse effects*
  • Male
  • Methylene Blue / therapeutic use
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms / drug therapy
  • Neoplasms / psychology
  • Odds Ratio
  • Prevalence
  • Retrospective Studies
  • Risk Factors


  • Antineoplastic Agents, Alkylating
  • Creatinine
  • Methylene Blue
  • Ifosfamide