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奥沙利铂治疗后的长期神经病变:对可逆转性定论的挑战。

Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility.

机构信息

Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.

出版信息

Oncologist. 2011;16(5):708-16. doi: 10.1634/theoncologist.2010-0248. Epub 2011 Apr 8.

Abstract

OBJECTIVES

Oxaliplatin-induced neuropathy is a significant and dose-limiting toxicity that adversely affects quality of life. However, the long-term neurological sequelae have not been adequately described. The present study aimed to describe the natural history of oxaliplatin-induced neuropathy, using subjective and objective assessments.

METHODS

From a population of 108 oxaliplatin-treated patients referred for neurological assessment in 2002-2008, 52.2% of the surviving patient cohort (n = 24) was available for follow-up at a median of 25 months post-oxaliplatin. Patients underwent a protocol that incorporated clinical assessment scales, patient questionnaires, standard electrodiagnostic assessments, and novel nerve excitability studies to precisely assess nerve function.

RESULTS

At follow-up, 79.2% of patients reported residual neuropathic symptoms, with distal loss of pin-prick sensibility in 58.3% of patients and loss of vibration sensibility in 83.3% of patients. Symptom severity scores were significantly correlated with cumulative dose. There was no recovery of sensory action potential amplitudes in upper and lower limbs, consistent with persistent axonal sensory neuropathy. Sensory excitability parameters had not returned to baseline levels, suggesting persisting abnormalities in nerve function. The extent of excitability abnormalities during treatment was significantly correlated with clinical outcomes at follow-up.

CONCLUSIONS

These findings establish the persistence of subjective and objective deficits in oxaliplatin-treated patients post-oxaliplatin, suggesting that sensory neuropathy is a long-term outcome, thereby challenging the literature on the reversibility of oxaliplatin-induced neuropathy.

摘要

目的

奥沙利铂诱导的周围神经病变是一种显著的剂量限制毒性,会对生活质量产生不利影响。然而,其长期神经后遗症尚未得到充分描述。本研究旨在使用主观和客观评估来描述奥沙利铂诱导的周围神经病变的自然病史。

方法

在 2002 年至 2008 年间接受神经评估的 108 例奥沙利铂治疗患者中,存活患者队列的 52.2%(n=24)在奥沙利铂治疗后中位数为 25 个月时可进行随访。患者接受了一项方案,该方案纳入了临床评估量表、患者问卷、标准电诊断评估以及新的神经兴奋性研究,以精确评估神经功能。

结果

在随访时,79.2%的患者报告仍存在神经病变症状,58.3%的患者存在远端针刺感觉丧失,83.3%的患者存在振动感觉丧失。症状严重程度评分与累积剂量显著相关。上肢和下肢的感觉动作电位幅度均无恢复,与持续性轴索性感觉神经病一致。感觉兴奋性参数未恢复到基线水平,表明神经功能仍存在异常。治疗期间兴奋性异常的程度与随访时的临床结局显著相关。

结论

这些发现证实了奥沙利铂治疗后的患者存在主观和客观缺陷的持续性,表明感觉神经病变是一种长期结局,从而对奥沙利铂诱导的周围神经病变可逆转的文献提出了挑战。

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