5-FU INDUCED ENCEPHALOPATHY DURING 5-FU CONTAINING REGIMEN FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA

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Abstract

Background

5-FU-induced encephalopathy was known as an uncommon toxicity during the treatment which contain with 5-FU. But there were few reports such as a clinical feature and risk factors of 5-FU-induced encephalopathy. We conducted retrospective case–control study to investigate the clinical feature and risk factor of them.

Methods

Data were collected from the medical record. The selection criteria were as follows: pathologically proven esophageal squamous cell carcinoma, patents who received 5-FU containing regimen in our hospital. The diagnostic criteria of the 5-FU induced encephalopathy includes: (i) development of encephalopathy during or shortly after the completion of 5-FU administration; (ii) exclusion of other metabolic factors that may affect consciousness and (iii) exclusion of an adverse effect by concomitant medications. 5-FU containing regimens include that 5-FU + CDDP with or without radiation, 5-FU + nedaplatin with or without radiation and 5-FU + CDDP + docetaxel.

Results

From January 2008 to March 2010, 317 patients were collected. Of 317 patients, the median age was 64 (range 36–79); male/female, 267/49; cStage I/IIA/IIB/III/IV, 63/19/53/91/85. The median and the total course of 5-FU containing regimen and were 2 (range 1–14) and 943. The object of first treatment was as follows: neoadjuvant (n = 114), definitive chemoradiotherapy (n = 110), palliative chemotherapy (n = 81) and others (N = 24). Nine patients (2.8%) were diagnosed as 5-FU encephalopathy. The median course and time to onset of encephalopathy was 3 course (range 1–4) and 5 days (range 3–6) from the start of 5-FU. Five of six patients who examined NH3 were observed the elevation of NH3. Head CT or MRI showed no abnormality in all patients. Univariate analysis showed that only age (>60) was the risk factor (P = 0.034). The creatinine level at days 4–6 during chemotherapy more elevated in the encephalopathy group (P = 0.004), and the Na level at days 4–6 more decreased in the encephalopathy group (P < 0.001).

Conclusions

5-FU encephalopathy was rare but more frequently occurred in aged patients. Transient change of creatinine and Na may be significance to the mechanisms of 5-FU encephalopathy.

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