周围神经方手足浸泡联合甲钴胺片防治长春新碱所致周围神经毒性临床研究

甘肃省肿瘤医院血液科，甘肃 兰州 730050

摘要：目的 观察周围神经方手足浸泡联合甲钴胺片防治长春新碱化疗所致周围神经毒性（CIPN）的临

床疗效。方法 采用随机数字表法将108例经长春新碱药物化疗的非霍奇金淋巴瘤患者分为治疗组、对照组、联合组各 36 例。3组均进行常规化疗（均首次使用 CHOP、R-CHOP、H-CAVD 方案），共 6个周期。对照组于化疗同时予甲钴胺片，每次 0.5 mg，每日 3 次，口服；治疗组在化疗同时予周围神经方手足浸泡，先手后足，每次 20 min，每日 2次；联合组在化疗同时予甲钴胺片及周围神经方，用法用量同前。均7d 为 1个疗程，连续治疗6个疗程。于化疗2、4、6 个周期评价3 组 CIPN发生率及程度，比较满意度。筛选周围神经毒性≥ Ⅱ度、已暂停化疗、自愿加入巩固治疗研究的患者50例，交替入巩固治疗组、巩固对照组各 25 例，巩固对照组口服甲钴胺片，巩固治疗组予周围神经方手足浸泡，用法用量同前，连续治疗 20 d，评价 2 组临床疗效及满意度。结果 化疗2个周期，治疗组与联合组CIPN 发生率明显低于对照组（P＜0.05）。化疗4个周期，联合组 CIPN发生率明显低于对照组（P＜0.01）；治疗组与联合组CIPN≥Ⅱ度的发生率明显低于对照组（P＜ 0.05）。化疗 6个周期，治疗组与联合组CIPN≥Ⅱ度的发生率明显低于对照组（P＜0.01）。治疗组满意率明显

高于对照组（P＜0.01）。对 CIPN≥Ⅱ度的患者巩固治疗，2组临床疗效比较差异无统计学意义（P＞0.05）；巩

固治疗组满意率明显高于巩固对照组（P＜0.01）。结论 周围神经方手足浸泡联合甲钴胺片对减轻 CIPN 疗效显著，可提高患者生活质量。关键词：周围神经方；甲钴胺；长春新碱；化疗所致周围神经毒性；手足浸泡DOI：10.3969/j.issn.1005-5304.2018.11.004

中图分类号：R277.75 文献标识码：A 文章编号：1005-5304(2018)11-0015-04

Clinical Study on Prevention and Treatment of CIPN Induced by Vincristine Through TCM Prescription of Peripheral Neuropathy Hand-food Soaking Combined with Mecobalamin

LIN Li, LI Ting, CUI Jie, LI Wen-ying, JIANG Jun-feng,WANG Yu-hong, PENG Xiao-juan

Hematology Department, Tumor Hospital of Gansu Province, Lanzhou 730050, China

Abstract: Objective To observe the clinical efficacy of prevention and treatment of chemotherapy induced peripheral neurpathy (CIPN) by vincristine via using TCM prescription of peripheral neuropathy hand-food soaking combined with mecobalamin. Methods Totally 120 patients with non-Hodgkin's lymphoma who all received chemotherapy drugs including vincristine were randomly divided into treatment group (36 cases), control group (36 cases) and combined treatment group (36 cases). All groups received routine treatment (all used CHOP, R-CHOP and H-CAVD plans for the first time), for 6 cycles of chemotherapy. The control group was given mecobalamin at the same time, 0.5 mg each time, oral administration, three times a day. The treatment group was given TCM prescription of peripheral neuropathy hand-foot soaking at the same time, hands first and feet later, 20 minutes each time, twice a day. The combined treatment group was given TCM prescription of peripheral neuropathy and mecobalamin at the same time, the same as the former method. 7 days were set as one treatment course, and all the treatment lasted for 6 cycles of chemotherapy. The incidence and degree of CIPN were evaluated in 2, 4, and 6 cycles of chemotherapy, and the satisfaction was compared. 50 patients of CIPN degree ≥Ⅱ were screened, paused chemotherapy, and participated

in consolidation treatment research. The 50 patients were assigned into treatment group (25 cases) and control group (25 cases). The control group took oral mecobalamin, and the treatment group used TCM prescription of peripheral neuropathy hand-foot soaking; the methods were the same as former methods, for 20 d. Clinical efficacy and satisfaction of both groups were evaluated. Results After the second cycle of chemotherapy, the incidence of CIPN in the treatment group and the combined treatment group were obviously lower than the control group (P<0.05). After the fourth cycle of chemotherapy, the incidence of CIPN in the combined treatment group were obviously lower than the control group (P<0.01); the incidence of CIPN degree ≥Ⅱ in the treatment group and combined treatment group were obviously lower than the control group (P<0.05). After the sixth cycle of chemotherapy, the incidence of CIPN degree ≥Ⅱ in the treatment group and combined treatment group were obviously lower than the control group

(P<0.01). The satisfaction rate of the treatment group was higher than the control group (P<0.01). For the consolidation therapy to patients of CIPN degree ≥Ⅱ, there was no statistical significance in clinical efficacy between the treatment group and the control group (P>0.05), but the satisfaction rate of the treatment group was higher than the control group (P<0.01). Conclusion TCM prescription of peripheral neuropathy hand-food soaking combined with mecobalamin can obviously relieve CIPN degree induced by vincristine, and improve the life quality of patients.

Keywords: TCM prescription of peripheral neuropathy; mecobalamin; vincristine; chemotherapy induced peripheral neurpathy; hand-foot soaking

长春新碱（VCR）是作用于 M 期的细胞周期特异性化疗药物，具有干扰微管蛋白合成的作用[1]，临床上多用于治疗血液系统肿瘤，如急性白血病、恶性淋巴瘤及部分实体肿瘤（乳腺癌、肺癌、软组织肉瘤、

脑瘤、神经母细胞瘤）[2]。但 VCR 不良反应中神经

毒性、骨髓抑制等限制了其临床应用[3]。这种具有剂量依赖性特点的周围神经毒性又称为化疗药物所致周围神经毒性（ chemotherapy-induced peripheral neurpathy，CIPN）[4]，多表现为一系列神经功能紊乱的症状和体征，最常见感觉神经病变，如远端肢体麻木、疼痛，手足套感等。虽然甲钴胺对CIPN 的防治

有一定疗效[5-6]，但该药更多应用于糖尿病所致的外

周神经病变[7-8]。本研究观察周围神经方手足浸泡联合甲钴胺片在 VCR 所致 CIPN 防治中的临床疗效及患者满意度，现报道如下。

1 资料与方法 1.1 一般资料

选择本院2016 年4月－2017年12月病理诊断为非霍奇金淋巴瘤，首次使用CHOP、R-CHOP、H-CAVD方案的肿瘤患者108例。采用随机数字表法分为治疗

组、联合组和对照组各36例。治疗组女性17 例，男

性 19 例，年龄 18～75 岁，平均年龄（49.86±16.39）岁，第 5 周期化疗中出现Ⅲ度 CIPN，无法耐受后续

化疗要求出组1例。联合组女性16例，男性 20 例，

年龄 18～75 岁，平均年龄（48.47±14.04）岁。对照

组女性19 例，男性17 例，年龄 19～75 岁，平均年龄

（52.83±16.36）岁，第 5周期化疗中出现CIPN≥Ⅱ度，

无法耐受后续化疗自动要求出组3 例。3组一般资料比较差异无统计学意义（P＞0.05），具有可比性。

将Ⅱ度以上 CIPN、自愿加入巩固治疗研究、已

停止化疗患者50 例（含上述4例出组病例），交替入治疗组和对照组各25例。治疗组女性11 例，男性 14例，年龄 18～72 岁，平均年龄（47.96±16.86）岁。

对照组女性13 例，男性 12 例，19～75 岁，平均年龄（56.64±15.38）岁。2 组一般资料比较差异无统计学意义（P＞0.05），具有可比性。本研究经本院伦理委

员会审查批准（A201601200001）。

1.2 西医诊断标准

参照《临床肿瘤内科手册》[1]制定非霍奇金淋巴瘤诊断标准。病理特点表现为病变淋巴结结构有不同程度破坏，瘤细胞形态基本为不同分化阶段的淋巴细胞，常以一种类型的细胞为主，同一病灶中可出现不同分化程度的瘤细胞。

1.3 纳入标准

①经病理诊断为非霍奇金淋巴瘤；②均无糖尿病、高血压、乙型肝炎、肝硬化、结核等疾病，卡氏

评分≥80分，肝功能、心脏功能、肾功能入组时处于

正常范围，预计生存期＞6个月；③年龄 18～75 岁，无智力及精神障碍，语言表达能力正常，对自身神经毒性相关症状及一般状况有判断能力；④对本研究知情并签署知情同意书。

1.4 排除标准

①既往接受过含 VCR 方案化疗，正使用洋地黄药物者；②有周围神经病变及相关症状者；③有脑转