Skip to main content

Advertisement

Log in

5-Fluorouracil can cross brain–blood barrier and cause encephalopathy: should we expect the same from capecitabine? A case report on capecitabine-induced central neurotoxicity progressing to coma

  • Short Communication
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose: Capecitabine is a relatively new oral fluoropyrimidine currently licensed for the treatment of colorectal and breast cancer. Results: It has the advantage of oral administration with good tolerability and comparable activity to intravenous 5-fluorouracil. Central neurotoxicity has been described in 5-fluorouracil-treated patients but there is little data regarding capecitabine. We report here a case of reversible capecitabine-induced encephalopathy progressing to coma. Discussion: Literature on fluoropyrimidine-related neurotoxicity will also be reviewed and possible mechanisms of the drug or its metabolites crossing the blood–brain barrier will be discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Anderson CM, Xiong W, Young JD, Cass CE, Parkinson FE (1996) Demonstration of the existence of mRNAs encoding N1/cif and N2/cit sodium/ nucleoside cotransporters in rat brain. Mol Brain Res 42:358–361

    Article  PubMed  CAS  Google Scholar 

  2. Bourke RS, West CR, Chheda G, Tower DB (1973) Kinetics of entry and distribution of 5-fluorouracil in cerebrospinal fluid and brain following intravenous injection in a primate. Cancer Res 33:1735–1746

    PubMed  CAS  Google Scholar 

  3. Cassidy J, Twelves C, Van Cutsem E, Hoff P, Bajetta E, Boyer M, Bugat R, Burger U, Garin A, Graeven U, McKendric J, Maroun J, Marshall J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schilsky RL, Capecitabine Colorectal Cancer Study Group (2002) First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol 13:566–575

    Article  PubMed  CAS  Google Scholar 

  4. Couch LS, Groteluschen DL, Stewart JA, Mulkerin DL (2003) Capecitabine-related neurotoxicity presenting as trismus. Clin Colorectal Cancer 3:121–123

    Article  PubMed  Google Scholar 

  5. Fox SB, Moghaddam A, Westwood M, Turley H, Bicknell R, Gatter KC, Harris AL (1995) Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in normal tissues: an immunohistochemical study. J Pathol 176:183–190

    Article  PubMed  CAS  Google Scholar 

  6. Mata JF, Garcia-Manteiga JM, Lostao MP, Fernandez-Veledo S, Guillen-Gomez E, Larrayoz IM, Lloberas J, Casado FJ, Pastor-Anglada M (2001) Role of the human concentrative nucleoside transporter (hCNT1) in the cytotoxic action of 5′-deoxy-5-fluorouridine, an active intermediate metabolite of capecitabine, a novel oral anticancer drug. Mol Pharmacol 59:1542–1548

    PubMed  CAS  Google Scholar 

  7. Niemann B, Rochlitz C, Herrmann R, Pless M (2004) Toxic encephalopathy induced by capecitabine. Oncology 66:331–335

    Article  PubMed  CAS  Google Scholar 

  8. [No authors listed] (1999) Case records of the Massachusetts General Hospital. weekly clinicopathological exercises. Case 24–1999. Neurologic disorder in a 65-year-old man after treatment of colon cancer. N Engl J Med 341:512–519

    Google Scholar 

  9. Phuphanich S, Jacobs M, Spiers A (1994) Response of recurrent brain metastases in malignant melanoma to 5-fluorouracil and interferon-alpha therapy. J Neuroimaging 4:114–116

    PubMed  CAS  Google Scholar 

  10. Roche Xeloda (capecitabine) data sheet

  11. Shehata N, Pater A, Tang SC (1999) Prolonged severe 5-fluorouracil-associated neurotoxicity in a patient with dihydropyrimidine dehydrogenase deficiency. Cancer Invest 17:201–205

    PubMed  CAS  Google Scholar 

  12. Takimoto CH, Lu ZH, Zhang R, Liang MD, Larson LV, Cantilena LR Jr, Grem JL, Allegra CJ, Diasio RB, Chu E (1996) Severe neurotoxicity following 5-fluorouracil-based chemotherapy in a patient with dihydropyrimidine dehydrogenase deficiency. Clin Cancer Res 2:477–481

    PubMed  CAS  Google Scholar 

  13. Tamai I, Tsuji A (2000) Transporter-mediated permeation of drugs across the blood–brain barrier. J Pharm Sci 89:1371–1388

    Article  PubMed  CAS  Google Scholar 

  14. Wang ML, Yung WK, Royce ME, Schomer DF, Theriault RL (2001) Capecitabine for 5-fluorouracil-resistant brain metastases from breast cancer. Am J Clin Oncol 24:421–424

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. Cunningham.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Formica, V., Leary, A., Cunningham, D. et al. 5-Fluorouracil can cross brain–blood barrier and cause encephalopathy: should we expect the same from capecitabine? A case report on capecitabine-induced central neurotoxicity progressing to coma. Cancer Chemother Pharmacol 58, 276–278 (2006). https://doi.org/10.1007/s00280-005-0159-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-005-0159-4

Keywords

Navigation