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Japanese Journal of Clinical Oncology Advance Access published online on January 25, 2006
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyi214
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© 2006 Foundation for Promotion of Cancer Research
Received August 1, 2005
Accepted November 11, 2005

Case Report

Intermediate Dose 5-Fluorouracil-Induced Encephalopathy

Yeon-A Kim 1, Hyun Cheol Chung 2, Hye Jin Choi 1, Sun Young Rha 3, Jin Sil Seong 4, and Hei-Cheul Jeung 3 *

1 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
2 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Cancer Metastasis Research Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
3 Cancer Metastasis Research Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
4 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea

* To whom correspondence should be addressed.
Hei-Cheul Jeung, E-mail: jeunghc1123{at}yumc.yonsei.ac.kr


  Abstract

As an acute neurotoxicity, high dose 5-fluorouracil (5-FU)-induced encephalopathy is well-known, but encephalopathy associated with lower dose is rarely reported. Here, we report a case of a male with anal cancer who was treated with 5-FU 1000 mg/m2, continuous infusion for 5 days q4 weeks. At the second and the fourth cycles of chemotherapy, sudden confusion, cognitive dysfunction and disorientation occurred during 5-FU infusion. They were accompanied by hyperammonemia in the absence of focal neurological deficits or structural abnormalities. These symptoms completely disappeared and the serum ammonia level returned to normal after discontinuation of 5-FU and conservative care. In order to investigate a possible deficit of dihydropyrimidine dehydrogenase (DPD), we checked its mRNA level before and after treatment using real-time PCR. The patient's pre-treatment level was 80% compared with reference group, and it was elevated up to 187% of initial after 5-FU treatment, implying that that his encephalopathy may be 5-FU catabolite type rather than DPD deficiency. In conclusion, we report that encephalopathy can develop even with the dose of 5-FU lower than ever reported, and it should be considered as a differential diagnosis for proper management.

Keywords: 5-fluorouracil; encephalopathy; anal cancer; hyperammonemia.
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