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肢体低温预防乳腺癌患者紫杉醇诱导的周围神经病变:一项初步研究

Limb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study.

作者信息

Sundar Raghav, Bandla Aishwarya, Tan Stacey Sze Hui, Liao Lun-De, Kumarakulasinghe Nesaretnam Barr, Jeyasekharan Anand D, Ow Samuel Guan Wei, Ho Jingshan, Tan David Shao Peng, Lim Joline Si Jing, Vijayan Joy, Therimadasamy Aravinda K, Hairom Zarinah, Ang Emily, Ang Sally, Thakor Nitish V, Lee Soo-Chin, Wilder-Smith Einar P V

机构信息

Department of Haematology-Oncology, National University Health System , Singapore , Singapore.

Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore; Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.

出版信息

Front Oncol. 2017 Jan 10;6:274. doi: 10.3389/fonc.2016.00274. eCollection 2016.

Abstract

BACKGROUND

Peripheral neuropathy (PN) due to paclitaxel is a common dose-limiting toxicity with no effective prevention or treatment. We hypothesize that continuous-flow limb hypothermia can reduce paclitaxel-induced PN.

PATIENTS AND METHODS

An internally controlled pilot trial was conducted to investigate the neuroprotective effect of continuous-flow limb hypothermia in breast cancer patients receiving weekly paclitaxel. Patients underwent limb hypothermia of one limb for a duration of 3 h with every paclitaxel infusion, with the contralateral limb used as control. PN was primarily assessed using nerve conduction studies (NCSs) before the start of chemotherapy, and after 1, 3, and 6 months. Skin temperature and tolerability to hypothermia were monitored using validated scores.

RESULTS

Twenty patients underwent a total of 218 cycles of continuous-flow limb hypothermia at a coolant temperature of 22°C. Continuous-flow limb hypothermia achieved mean skin temperature reduction of 1.5 ± 0.7°C and was well tolerated, with no premature termination of cooling due to intolerance. Grade 3 PN occurred in 2 patients (10%), grade 2 in 2 (10%), and grade 1 in 12 (60%). Significant correlation was observed between amount of skin cooling and motor nerve amplitude preservation at 6 months ( < 0.0005). Sensory velocity and amplitude in the cooled limbs were less preserved than in the control limbs, but the difference did not attain statistical significance. One patient with a history of diabetes mellitus had significant preservation of compound muscle action potential in the cooled limb on NCS analysis.

CONCLUSION

This study suggests that continuous limb hypothermia accompanying paclitaxel infusion may reduce paclitaxel-induced PN and have therapeutic potential in select patients and warrants further investigation. The method is safe and well tolerated.

摘要

背景

紫杉醇所致周围神经病变(PN)是一种常见的剂量限制性毒性反应,目前尚无有效的预防或治疗方法。我们推测持续血流肢体低温可减轻紫杉醇诱导的PN。

患者与方法

进行了一项自身对照的前瞻性试验,以研究持续血流肢体低温对接受每周紫杉醇治疗的乳腺癌患者的神经保护作用。每次输注紫杉醇时,患者一侧肢体进行3小时的肢体低温治疗,对侧肢体作为对照。PN主要在化疗开始前、化疗1、3和6个月后通过神经传导研究(NCS)进行评估。使用经过验证的评分监测皮肤温度和对低温的耐受性。

结果

20例患者在冷却液温度为22°C的情况下共进行了218个周期的持续血流肢体低温治疗。持续血流肢体低温使平均皮肤温度降低了1.5±0.7°C,耐受性良好,未因不耐受而提前终止降温。3级PN发生在2例患者(10%)中,2级发生在2例(10%)中,1级发生在12例(60%)中。在6个月时,观察到皮肤降温量与运动神经振幅保留之间存在显著相关性(<0.0005)。冷却肢体的感觉速度和振幅保留程度低于对照肢体,但差异无统计学意义。1例有糖尿病病史的患者在NCS分析中冷却肢体的复合肌肉动作电位有显著保留。

结论

本研究表明,紫杉醇输注时持续肢体低温可能减轻紫杉醇诱导的PN,对特定患者具有治疗潜力,值得进一步研究。该方法安全且耐受性良好。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db88/5222823/d6f1f65c9d44/fonc-06-00274-g001.jpg

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