5-FU-induced neurotoxicity in cancer patients with profound DPD deficiency syndrome: a report of two cases
5-FU-induced neurotoxicity in cancer patients with profound DPD deficiency syndrome: a report of two cases
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DOI：
10.1007/s00280-011-1666-0
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发表时间：
2011-09-01
影响因子：
3
通讯作者：
Peytel, Eric
中科院分区：
文献类型：
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作者：
Cordier, Pierre-Yves;Nau, Andre;Peytel, Eric
5-氟尿嘧啶（5-FU）是治疗成人各种实体瘤的主要药物，包括消化道癌和头颈癌。5-FU相关毒性通常包括血液学、消化道和皮肤特征。此外，5-FU被描述为对患者具有潜在的神经毒性，但这些副作用在临床实践中非常罕见。在此，我们报告了两例在接受第一个疗程的5-FU化疗的患者中发生的突发和不可预测的药物诱导的神经毒性。这些患者都没有任何神经系统疾病病史，并且都按照标准方案（患者1和2分别接受LV-5-FU 2和TPF）进行治疗。神经毒性包括嗜睡，急性意识模糊和构音障碍的第一个病人和癫痫发作，意识模糊和代谢性脑病的迹象，第二个。此外，观察到典型的5-FU相关重度毒性（例如中性粒细胞减少和粘膜）。在支持治疗下，2例患者均从这些神经毒性中缓慢恢复。假设5-FU过度暴露可以解释所遇到的重度毒性。为了验证这一假设，我们回顾性地评估了这些患者的二氢嘧啶脱氢酶（DPD）活性的表型基础上的尿嘧啶，二氢尿嘧啶（U/UH 2）的血浆中的比例的评价显示了深刻的DPD缺乏综合征在这两个patients.These情况下，5-FU标准剂量给药可能会导致强烈的过度，负责观察到的严重毒性，包括神经系统的功能。这意味着DPD缺乏可导致5-FU治疗患者的神经毒性，并主张在开始任何含5-FU的化疗之前进行DPD缺乏的前瞻性筛查，以防止将来发生此类副作用。
5-Fluorouracil (5-FU) is a mainstay for treating various solid tumours in adults, including digestive and head and neck cancers. 5-FU-related toxicities usually include haematological, digestive and cutaneous features. Additionally, 5-FU has been described as being potentially neurotoxic in patients, but these side effects are quite rare in clinical practice. Here, we report two cases of sudden and unpredictable drug-induced neurotoxicities that occurred in patients undergoing their first course of 5-FU-based chemotherapy.None of these patients had any previous neurological disorder history, and both were treated following standard regimen (LV-5-FU2 and TPF for patient 1 and 2, respectively). Neurotoxicity included drowsiness, acute confusion plus dysarthria for the first patient and seizure, confusion and signs of metabolic encephalopathy for the second one. In addition, typical 5-FU-related severe toxicities (e.g. neutropenia and mucosities) were observed. Both patients slowly recovered from these neurological toxicities under supportive treatment. It was assumed that overexposure to 5-FU could explain the severe toxicities encountered. To test this hypothesis, we retrospectively evaluated the dihydropyrimidine dehydrogenase (DPD) activity of these patients on a phenotypic basis.Evaluation of the uracil-to-di-hydrouracil (U/UH2) ratio in plasma revealed a profound DPD deficiency syndrome in both patients.These cases suggest that 5-FU standard dosage administration may lead to strong overexposure, responsible for the severe toxicities observed, including the neurological features. It implies that DPD deficiency can cause neurotoxicity in 5-FU-treated patients and advocates for the prospective screening of DPD deficiency before starting any 5-FU-containing chemotherapy so as to prevent such side effects in the future.