Wernicke-Korsakoff-like syndrome in patients with colorectal carcinoma treated with high-dose doxifluridine (5′-dFUrd)

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Abstract
5''-dFUrd (doxifluridine) is a new fluoropyrimidine that may have a higher antitumor effect and less side effects than 5-FU. In this study 15 patients with advanced colorectal carcinoma, one with renal carcinoma, one with carcinoid and one with advanced carcinoma of unknown origin, were randomly assigned to receive 5''-dFUrd 5 g/m2 or 3 g/m2 as a 1-h infusion for 5 days in 3 cycles at intervals of 4 weeks. The patients had repeated neurological and neurophysiological examinations before and during the treatment. Ten patients developed symptoms of toxicity of the central nervous system (CNS), with cerebellopathy and encephalopathy resembling a Wernicke-Korsakoff syndrome. The neurotoxicity was dose related, affecting 7 to 8 patients in the high dosage group and 3 of 9 patients in the low dosage group. The symptoms generally started at the end of the second week of the cycle with unsteadiness and diplopia, and progressed to the fourth week with ataxia, confusion and EEG-changes, becoming more pronounced with increasing number of cycles. After the treatment there was normalisation within 4-8 weeks. Cachectic patients and patients with a pathological EEG before treatment seem to represent a high-risk group for CNS-symptoms. EEG may be helpful in early diagnosis of CNS-toxicity.