title: [Incidence and risk factors for ifosfamide-related encephalopathy in sarcoma patients].
abstract: BACKGROUND
  Ifosfamide remains one of the major cytotoxic drugs for sarcoma management. Ifosfamid-related encephalopathy (IRE) is a rare but severe adverse event, without clearly identified risk factors.
  
  
  METHODS
  We have carried out a single-center, retrospective study to assess the occurrence and the risk factors for IRE after the two first cycles of chemotherapy. We have collected the data-describing patients, biological data, tumors characteristics (histology, leptomeningeal metastasis) and ifosfamide administration modalities.
  
  
  RESULTS
  From September 2008 to November 2013, we have identified 8 IRE out of 187 patients (4.2% [CI95%: 1.8-8.2]). The median age was 27 (0-78). Histologies were adult soft tissue sarcomas (78 patients), osteosarcoma (48), ewing sarcoma (41) and rhabdomyosarcoma (26). Most of factors were not associated with IRE. Only 8 patients have received aprepitant, none of them experienced IRE. Under univariate analysis, the risk factors for IRE were: PS≥2 (OR=9.52 [CI95%: 2.38-38.80]), albumin≤36g/L (OR=9.79 [CI95%: 1.19-80.26]), leptomeningeal metastasis (OR=13.20 [CI95%: 2.76-63.19]), 4 or 5 successive days of ifosfamide administration (OR=6.00 [CI95%: 1.40-25.60]). Under multivariate analysis, the risk factors for IE were: PS≥2 (OR=16.00 [IC95%: 2.80-67.00]), leptomeningial metastasis (OR=23.56 [IC95%: 2.01-456.80]) and 4 or 5 days of ifosfamide administration (OR=57.45 [IC95%: 1.66-35.00]).
  
  
  CONCLUSIONS
  Ifosfamide administration must be given with caution in patients with poor performans status. A 4 to 5 days fractioned ifosfamide and leptomeningeal metastasis seems associated with increased risk for IRE, whatever the total administered dose.
authors.affiliation: Centre Oscar-Lambret, département d'oncologie médicale, 3, rue Combemale, 59020 Lille cedex, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Stern
authors.affiliation: Service de pharmacie, centre Oscar-Lambret, 3, rue Combemale, 59020 Lille cedex, France.
authors.forename: Ilyes
authors.initials: I
authors.lastname: Sakji
authors.affiliation: Centre Oscar-Lambret, unité de pédiatrie, 3, rue Combemale, 59020 Lille cedex, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Defachelles
authors.affiliation: Centre Oscar-Lambret, unité de pédiatrie, 3, rue Combemale, 59020 Lille cedex, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Lervat
authors.affiliation: Centre Oscar-Lambret, département d'oncologie médicale, 3, rue Combemale, 59020 Lille cedex, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ryckewaert
authors.affiliation: Service de pharmacie, centre Oscar-Lambret, 3, rue Combemale, 59020 Lille cedex, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Marliot
authors.affiliation: Centre Oscar-Lambret, département d'oncologie médicale, 3, rue Combemale, 59020 Lille cedex, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Peugniez
authors.affiliation: CHU de Lille, University Lille, Inserm, U1171 - Degenerative & vascular cognitive disorders, 59000 Lille, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Deplanque
authors.affiliation: Centre Oscar-Lambret, département d'oncologie médicale, 3, rue Combemale, 59020 Lille cedex, France; CHRU de Lille, SIRIC OncoLille, 2, avenue Oscar-Lambret, 59037 Lille cedex, France. Electronic address: n-penel@o-lambret.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Penel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects*; D001927:Brain Diseases / Q000139:chemically induced* / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D034141:Hypoalbuminemia / Q000150:complications; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects*; D015994:Incidence; D007223:Infant; D008297:Male; D008577:Meningeal Neoplasms / Q000556:secondary; D008875:Middle Aged; D016017:Odds Ratio; D012516:Osteosarcoma / Q000188:drug therapy* / Q000556:secondary; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000556:secondary; D012307:Risk Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide
keywords: Encephalopathy; Encéphalopathie; Ifosfamide; Sarcoma; Sarcome; Toxicity; Toxicité