Functional and Pharmacokinetic Outcomes after a Single Intravenous Infusion of Recombinant Human Erythropoietin in Patients with Malignant Extradural Spinal Cord Compression

Loblaw, D.A.; Holden, L.; Xenocostas, A.; Chen, E.; Chander, S.; Cooper, P.; Chan, P.C.; Wong, C.S.

doi:10.1016/j.clon.2006.10.009

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Volume 19, Issue 1 , Pages 63-70, February 2007

Functional and Pharmacokinetic Outcomes after a Single Intravenous Infusion of Recombinant Human Erythropoietin in Patients with Malignant Extradural Spinal Cord Compression

D.A. Loblaw
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
- Author for correspondence: D. A. Loblaw, Department of Radiation Oncology, Sunnybrook and Women's College Health Sciences Centre, T2-107, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Tel: +1-416-480-4806; Fax: +1-416-480-6002.
L. Holden
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
A. Xenocostas
- Division of Hematology, London Health Science Center, University of Western Ontario, London, Ontario, Canada
E. Chen
- Department of Medical Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario, Canada
S. Chander
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
P. Cooper
- Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
P.C. Chan
- Department of Clinical Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
C.S. Wong
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada

Received 2 March 2006; received in revised form 5 October 2006; accepted 23 October 2006.

Abstract

Aims

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.

Materials and 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 1500IU/kg intravenously over 30min followed by a standardised dexamethasone and radiotherapy protocol. A lumbar puncture and venipuncture were carried out 24–30h 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 92.5mIU/ml, range 17.8–214.0mIU/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.

Key words: Erythropoietin, malignant spinal cord compression, outcomes research, palliation, radiotherapy