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聚(ADP-核糖)聚合酶抑制剂能否缓解癌症患者的紫杉醇诱导的周围神经病变?

Can Poly (ADP-Ribose) Polymerase Inhibitors Palliate Paclitaxel-Induced Peripheral Neuropathy in Patients With Cancer?

作者信息

Balko Ryan A, Hendrickson Andrea Wahner, Grudem Megan E, Klampe Carolyn M, Jatoi Aminah

机构信息

1 Department of Medicine, Mayo Clinic, Rochester, MN, USA.

2 Department of Oncology, Mayo Clinic, Rochester, MN, USA.

出版信息

Am J Hosp Palliat Care. 2019 Jan;36(1):72-75. doi: 10.1177/1049909118786958. Epub 2018 Jul 8.

Abstract

BACKGROUND

: Paclitaxel-treated patients can suffer from years of peripheral neuropathy with pain, numbness, and tingling. Promising preclinical data with poly (ADP-ribose) polymerase (PARP) inhibitors led us to explore this class of agents to palliate this neuropathy.

METHODS

: We relied on a completed trial that tested the antineoplastic effects of veliparib (NCT01012817). Data from patients who had been enrolled on NCT01012817, who previously received paclitaxel, and who had completed a validated pain assessment instrument were evaluated for improvement in their pain scores.

RESULTS

: All 34 eligible patients were women, and all had a metastatic gynecological malignancy. On a 10-point scale (higher numbers indicative of worse pain), the average baseline score was 3.6 (range: 0-7). Seven patients (21%; 95% confidence interval: 9%-38%) manifested a drop in pain score (1 score lower than baseline followed by at least one consecutive value also below baseline). Of note, no patients initiated other therapy for neuropathy while on NCT01012817.

CONCLUSION

: The PARP inhibitors merit further study for chemotherapy-induced peripheral neuropathy. For patients suffering from peripheral neuropathy, these putative palliative effects might prompt earlier consideration of a PARP inhibitor as part of cancer treatment.

摘要

背景

接受紫杉醇治疗的患者可能会遭受数年的周围神经病变,出现疼痛、麻木和刺痛感。聚(ADP-核糖)聚合酶(PARP)抑制剂的临床前数据很有前景,这促使我们探索这类药物来缓解这种神经病变。

方法

我们依据一项已完成的试验,该试验测试了维利帕尼的抗肿瘤作用(NCT01012817)。对纳入NCT01012817、先前接受过紫杉醇治疗且完成了一项经过验证的疼痛评估工具的患者数据进行评估,以观察其疼痛评分的改善情况。

结果

所有34例符合条件的患者均为女性,且均患有转移性妇科恶性肿瘤。在10分制量表(分数越高表明疼痛越严重)上,平均基线评分为3.6(范围:0 - 7)。7例患者(21%;95%置信区间:9% - 38%)的疼痛评分下降(比基线低1分,随后至少有一个连续值也低于基线)。值得注意的是,在参与NCT01012817试验期间,没有患者开始接受其他治疗神经病变的疗法。

结论

PARP抑制剂在化疗引起的周围神经病变方面值得进一步研究。对于患有周围神经病变的患者,这些假定减轻症状的作用可能会促使人们更早地考虑将PARP抑制剂作为癌症治疗的一部分。

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