title: Functional and pharmacokinetic outcomes after a single intravenous infusion of recombinant human erythropoietin in patients with malignant extradural spinal cord compression.
abstract: OBJECTIVE
  To determine the cerebrospinal fluid concentrations and the functional and pain outcomes after a single intravenous infusion of erythropoietin at the start of a standard radiotherapy and steroid protocol.
  
  
  METHODS
  Ten paraparetic patients with malignant extradural spinal cord compression who were eligible for radiotherapy, lumbar puncture and intravenous epoetin alpha were enrolled. The patients received epoetin alpha 1500 IU/kg intravenously over 30 min followed by a standardised dexamethasone and radiotherapy protocol. A lumbar puncture and venipuncture were carried out 24-30 h after the epoetin alpha infusion. The patients were followed closely at defined intervals.
  
  
  RESULTS
  Erythropoietin was detectable in the cerebrospinal fluid in all eight patients sampled (median 92.5 mIU/ml, range 17.8-214.0 mIU/ml). Before treatment, eight patients were non-ambulatory and two patients were ambulatory with assistance. After treatment, eight (80%, 95% confidence interval [CI] 44-97%) improved at least one functional class and recovered or maintained ambulation. Five of seven patients (71%; 95% CI 29-96%) with objective sensory deficits and one of seven (14%; 95% CI 0-58%) catheter-dependent patients recovered. Overall, 78% (95% CI 40-97%) had a pain response.
  
  
  CONCLUSIONS
  After an intravenous infusion of epoetin alpha, radiotherapy and steroids, high concentrations of erythropoietin were detectable in the cerebrospinal fluid. Patients with malignant extradural spinal cord compression showed encouraging improvements in neurological function and pain.
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. andrew.loblaw@sunnybrook.ca
authors.forename: D A
authors.initials: DA
authors.lastname: Loblaw
authors.forename: L
authors.initials: L
authors.lastname: Holden
authors.forename: A
authors.initials: A
authors.lastname: Xenocostas
authors.forename: E
authors.initials: E
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Chander
authors.forename: P
authors.initials: P
authors.lastname: Cooper
authors.forename: P C
authors.initials: PC
authors.lastname: Chan
authors.forename: C S
authors.initials: CS
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000627:therapeutic use; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage* / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology; D010166:Palliative Care; D020335:Paraparesis / Q000209:etiology; D011994:Recombinant Proteins; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000209:etiology / Q000532:radiotherapy; D013125:Spinal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000532:radiotherapy; D015996:Survival Rate
chemical_list: D005938:Glucocorticoids; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D003907:Dexamethasone