外用和血通痹方治疗抗肿瘤化疗药所致周围神经毒性的临床疗效观察
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摘要
目的
     分析抗肿瘤化疗药所致周围神经毒性的中医病因病机,评估外用和血通痹方加减对抗肿瘤化疗药所致周围神经毒性的治疗效果及其安全性,为中医药在化疗药物所致周围神经毒性规范化治疗上的应用提供相关理论和实践参考。方法
     采用前瞻性自身前后对照方法,收集合格病例40例,予外用和血通痹方加减治疗抗肿瘤化疗药所致周围神经毒性。参考NCI周围神经毒性分级标准,观察用药前后神经毒性分级变化及起效时间,评估治疗效果。结果
     ①40例患者中以夹杂气虚、血虚多见(共占75%),分级多以Ⅰ度毒性为主(47.5%)。其中应用泰素类化疗者多以夹杂血虚为主,表现为四肢末梢麻木尤甚,感觉袖套样减退;应用希罗达化疗者多以夹杂血热为主,表现为指趾色素沉着,可伴有脱屑;应用奥沙利铂化疗者多以夹杂寒凝为主,四肢畏冷,麻木疼痛等症遇寒加重。40例患者中舌暗者居多(82.5%),脉涩(52.5%)、虚(22.5%)、细(21/40,52.5%)居多。②经中医药辨证治疗,治愈21例,显效3例,有效15例,无效1例,总有效率97.5%。③泰素类组、希罗达组、奥沙利铂组、奥沙利铂+希罗达组之间疗效无明显差异(P=0.137)。气虚型、血虚型、血热型、寒凝型之间疗效有差异(P=0.032);其中气虚型、血虚型分别与血热型比较,疗效有显著性差异。④不同分级神经毒性治疗的平均起效时间之间有差异(F=4.646,P=0.016);Ⅲ级神经毒性与Ⅰ、Ⅱ级治疗的平均起效时间之间有显著性差异,时间明显延长。不同化疗用药组的治疗平均起效时间之间无差异。血热型与其余三型相比起效时间有差异,起效时间延长。⑤不同疗程疗效比较有显著差别,疗程越长,疗效越好,治愈率越高(P=0.000)。⑥随访2个月,未发现毒性复发情况。结论
     ①化疗所致周围神经毒性多以Ⅰ级毒性为主;在证型夹杂方面,以气虚型和血虚型多见;患者常伴见舌暗、脉涩、虚细等表现,从侧面佐证了神经毒性患者气血不足、脉络瘀滞的病机。②本方案辨证加减治疗抗肿瘤化疗药所致周围神经毒性有确切的疗效:能显著改善患者神经毒性症状,并能稳定疗效;气虚型和血虚型这两种证型的疗效尤为明显。此外,本研究方案安全性好,随访巩固疗效亦可。从而初步显示了本方案在降低化疗所致周围神经毒性副反应方面的优势。
Purpose:
     To analyses etiology and pathogenesis in TCM of peripheral nerve toxicity caused by anti-tumor chemotherapy drugs, then evaluate the treatment and security of external using Hexue Tongbi Fang to treat peripheral nerve toxicity caused by anti-tumor chemotherapy drugs, in order to provide relevant theoretical and practical reference in the Chinese medicine Standardized therapy of peripheral nerve toxicity caused by anti-tumor chemotherapy drugs.
     Methods:
     Using prospective and self-controlled research methods, collect a total of 40 cases, give the external using of Hexue Tongbi Fang to treat peripheral nerve toxicity caused by anti-tumor chemotherapy drugs. Then formulate a standard of peripheral nerve toxicity according to NCI, contrast the changes of peripheral nerve toxicity before and after treatment period and the onset time, for the sake of evaluating the efficafy of Chinese medicine.
     Results:
     ①In 40 cases, the most common types of TCM syndrome is qi deficiency and blood deficiency Type(75%), then the most common grades of peripheral nerve toxicity is Grade 1(47.5%). Among them which used the chemotherapy drugs such as Taxol are most including blood deficiency syndrome, showing numb of distal limbs, diminished sense of sleeve-like. The patients which used the chemotherapy drugs such as Xeloda are most including blood heat syndrome, showing limb peripheral pigmentation and desquamation. The patients which used the chemotherapy drugs such as L-OHP are most including cold congealing syndrome, showing cold of the limbs and numb pain which may increase by cold.
     ②In 40 cases of Chinese medicine group,21 cases were cured,3 cases were clear improved,15 cases were improved(the improvement rate was 97.5%,2 cases were ineffective. Total effective rate was 97.5%.
     ③In regard of drug group among Taxol, Xeloda, L-OHP, L-OHP+Xeloda, showing no significant difference (P=0.137). In regard of the types of TCM syndrome, we found that it shows significant difference in efficacy between blood deficiency Type and blood heat Type, or between blood deficiency Type and blood heat Type.④In regard of the onset time of GradeⅠ-Ⅲshowing significant difference (F=4.646, P=0.016),GradeⅢ's onset time are much longer than GradeⅡand Grade I's. In regard of the onset time of drug groups showing no significant difference. In regard of the onset time of types of TCM syndrome showing significant difference, the Xuere Type needed more time to recovery.
     ⑤In regard of treatment cycles shows significant difference, the longer course of treatment, the better result of treatment (P=0.000)
     ⑥We followed up the patients for 2 months, didn't recrudescence. Conclusion:
     ①The most common grades of peripheral nerve toxicity is "GradeⅠ", and the most common types of TCM syndrome are qi deficiency Type and blood deficiency Type. Most of patients have those symptoms of blood stasis, such as painful dark tongue、deep thready pulse, it may coincide the hypothesis that most patients has the physical condition of Qi-Blood deficiency and obstruction of meridian and collateral.
     ②The TCM therapy in this study has definite therapeutic effect to peripheral nerve toxicity caused by anti-tumor chemotherapy drugs:It can improve patients'subjective symptoms significantly, reduce peripheral nerve toxicity. Compare with other types of TCM syndrome, qi deficiency Type and blood deficiency Type have more significant efficafy. Furthermore, The TCM therapy had no side effect. Altogether, it preliminary shows the advantages of Chinese medicine in reducing peripheral nerve toxicity caused by anti-tumor chemotherapy drugs.
引文
[1]周岱翰,周宜强,黄耀权等.临床中医肿瘤学[M].北京:人民卫生出版社,2003
    [2]黄兆胜,李祖伦,常章富等.中药学[M].北京:人民卫生出版社,2002
    [3]张汀荣,许晨,沈伟生等.参附注射液联合肉桂防治奥沙利铂神经毒性疗效观察[J].中国药房,2006,17(20):1570-1571.
    [4]刘展华,吴玉生,谭开基.川芎嗪预防奥沙利铂致神经毒性反应14例[J].实用中医药杂志,2003,19(11):575-575.
    [5]陈旻,孟志强,李小平.生脉注射液治疗草酸铂所致神经毒性反应60例临床观察[J].中华实用中西医杂志,2005,18(19):1137-1138.
    [6]钱永红.生脉注射液防治草酸铂神经毒性疗效观察[J].基层医学论坛,2008,12(7):222-223.
    [7]刘海哗,周洁.癌复康1号减轻草酸铂所致周围神经毒性临床观察[J].河北中医,2008,30(6):597-597.
    [8]戴虹,潘宇,王晓露.补阳还五汤加味治疗草酸铂化疗后周围神经毒性42例[J].实用中医内科杂志,2006,20(5):518-519.
    [9]常忠莲,万冬桂.加味补阳还五汤防治希罗达所致手足综合征45例[J].中国中医药信息杂志,2005,12(6):63-64.
    [10]孔颖泽,徐珍,冷嘉兴.黄芪桂枝五物汤加减治疗奥沙利铂所致神经毒性的体会[J].河北中医,2005,27(12):923-924.
    [11]朱宝龙.温经汤防治奥沙利铂外周神经毒性疗效观察[J].现代中西医结合杂志,2008,17(34):5320.
    [12]阎丽珠,周洁.益气温阳活血法治疗奥沙利铂神经毒性42例[J].世界中西医结合杂志,2007,2(5):287-288,290.
    [13]万冬桂.化疗药物中枢性及周围性神经毒性的中西医结合防治[J].中级医刊.1998.33(11):13-15.
    [14]李燕,王秀芹,赵晓英.鸡血藤汤治疗长春新碱致神经毒性21例[J].新中医.2002.34(11):52-53.
    [15]杨侠.中药熏蒸治疗奥沙利铂化疗后周围神经毒性反应的护理[J].中华现代护理杂志,2008,14(17):1874-1875.
    [16]张俊英,王爱英,申瑞霞.中药煎洗防治紫杉醇所致神经毒性38例[J].中国中西医结合杂志.2008.28(9):827
    [17]俞新燕.中草药浸泡防治卡培他滨致手足综合征的疗效观察及护理[J].护理与康复,2008,7(4):310-311.
    [18]Kelly H, Goldberg RM. Systemic therapy for metastatic colorectal cancer: curent options, current evidence[J]. Clin Oncol,2005,23:4553-4560.
    [19]Aggarwal S, Chu E. Current therapies for advanced colorectal cancer [J]. Oncology (Williston Park),2005,19:589-595.
    [20]Cassidy J, MissetJL. Oxaliplatin-related side effects:characteristics and management [J]. Semin Oncol,2002,29(5-15):11-20.
    [21]李洁,金懋林,杨伯秦等.乐沙定联合氟脲嘧啶、甲酰四氢叶酸治疗进展期大肠癌21例分析[J].中国肿瘤临床,2001,28(4):265-266.
    [22]Misset JL. Oxaliplatin in practice[J]. BrJ Cancer,1998,77(14):144.
    [23]Wilson RH, Lehky T, Thomas RR, et al. Acute oxaliplatin-induced peripheral nerve hyperexcitability[J]. Clin Oncol,2002,20(13):1767.
    [24]Armand JP,孙燕,管忠震等.草酸铂(奥沙利铂)治疗大肠癌的研究进展[J].癌症,1999,18(6):624.
    [25]Gamelin E, Gamelin L, Bossi L, et al. Clinical aspects and molecular basis of oxaliplatin neurotoxieity:Current management and development of preventive measures[J]. Semin Oncol,2002,29:21.
    [26]Adelsberger H, Quasthof S, Grosskreutz J, et al. The chemotherapeutic oxaliplatin alters voltage-gated Na(+)channel kinetics on rat sensory neurons. Eur J Pharmacol,2000,406(1):25-32.
    [27]王墨培,马力文,张淑兰等.含草酸铂化疗方案治疗大肠癌神经毒性的临床研究[J].肿瘤防治杂志,2004,11(2):168-170.
    [28]Mckeage MJ, Hsu T, Screnci D, et al. Nucleolar damage correlates with neurotoxicity induced by different platinum drugs [J]. Br J Cancer,2001, 85(8):1219-1225.
    [29]Cavaletti G, Pezzoni G, Pisano C, et al. Cisplatin induced peripheral neurotoxicity in rats reduces the circulating levels of nerve growth factor [J]. Neurosci Lett,2002,322(2):103-106.
    [30]Grolleau F, Gamelin L, Boisdron, et al. A possible explanation for a neurotoxic fleet of the anticancer agent oxaliplatin on neuronal voltage-gated sod ium channels[J]. Neurophyscal,2001,85(20):2293-2297.
    [31]Lehky TJ, Leonard GD, Wilson RH, et al. Oxaliplatin-induced neurotoxicity: acute hyperexcitability and chronic neuropathy[J]. Muscle Nerve,2004, 29(3):387.
    [32]Donzelli E, Carfi M, Miloso M, et al. Neurotoxicity of platinum compounds:
    comparison of the effects of cisplatin and oxaliplatin on the human neurohlastoma cell line SH-SY5Y[J], J Neurooncol,2004,67(1-2):65-73.
    [33]廖明阳,马华智.紫杉醇的临床毒副作用分析[J].解放军药学学报.1999.15(5):25-27.
    [34]李文军.紫杉醇不良反应文献综述[J].药物流行病学杂志,2002,11(4):187-188.
    [35]梁昱.抗肿瘤化疗药物所致的神经毒性研究进展[J],临床内科杂志.2006.23(6):430-432.
    [36]Kris MG, Joseph P, Gralla RJ, et al. Phase Iirial of taxol given as a 3 hours infusion every 21 days[J], Cancer Treat Rep.1996,39(1):368.
    [37]杨益阶.肿瘤化疗药物的神经毒性[J],武汉医学杂志.1994.18(1):63-64.
    [38]Gelderblom H, Verwei j J, Nooter K, et al. Cremophor EL:The drawbacks and advantages of vehicle selection for drug formulation [J]. Eur J Cancer.2001.37 (13):.1590.
    [39]马新成,魏长凤,岳建华.卡培他滨[J],齐鲁药事.2005.24(10):638.
    [40]王琰,徐瑞荣.希罗达等致手足综合征中、西医防治措施研究进展[J].中国中西医结合杂志,2007,27(2):182-184.
    [41]Lokich JJ, Moore C.Chemotherapy-associated palmar-plantar erythrodysesthesia syndrome. Ann Intern Med 1984,101(6):798-799.
    [42]Abushullaih S, Saad ED, Munsell M, et al. Incidence and severity of hand-foot syndrome in colorectal cancer patients treated with capecitabine:a single-institution experience[J]. Cancer Invest,2002,20(1):3-10.
    [43]孙燕,周际昌.临床肿瘤内科手册[M].北京:人民卫生出版社,1996.
    [44]王涛,江泽飞,宋三泰等.希罗达治疗乳腺癌所致手足综合征的发生规律及临床处理[J].癌症进展杂志,2004,2(4):257-260.
    [45]Levi F, Misset JL, Brienza S, et al. Achronopharmacologic phase Ⅲ Clinical trial with 5-fluorouracil, folinic acid and oxaliplatin using an ambulatory multichannel programmable pump[J]. High antitumor effectives against metastatic colorectal cancer. Cancer,1992,69:893.
    [46]Extra JM, Marty M, Bricnza S, et al. Pharmacokinetics and safety profile of oxaliplatin[J]. Semin Oncol,1998,25:13.
    [47]马飞,袁凡,徐泉等.奥沙利铂所致急性神经毒性的临床分析及其治疗[J].临床肿瘤学杂志,2005,10(5):533-535.
    [48]Cavaletti G,Trediei G, Petruccioli MG, et al. Effects of different schedules of oxaliplatin treatment on the peripheral nervous systern ofthe rat[J]. Eur J Cancer,2001,37(18):2457.
    [49]赵惠,任芳,郭艳辉.紫杉醇周围神经毒性临床观察[J],中国实用医药.2008.3(13):136-137.
    [50]Heo YS, Chang HM, Kim TW, et al. Hand-foot syndrome in patients treated with apecitabine-containing combination chemotherapy[J]. J Clin Pharmacol,2004,44(10):1166-1172.
    [51]Blum JL, Jones SE, Buzdar AU,et al. Multicenter phase Ⅱ study of capecitabine in paclitaxel-refractory etastatic breast cancer[J]. J Clin Oncol,1999,17(2):485-493.
    [52]Siliprandi R, Canella R, Carmignoto G. Nerve growth factor promotes functional recovery of retinal ganglion cells after ischemia[J]. Invest Ophthalmol Vis Science,1993,34(12):3232-3245.
    [53]Abe T, Morgan DA, Gutterman DD. Protective role of nerve growth factor against postischemic dysfunction of sympathetic coronary innervation[J]. Circulation,1997,95(1):213-220.
    [54]Aloe L,Manni L,Properzi F,et al. Evidence that nerve growth factor promotes the recovery of peripheral neuropathy induced in mice by cisplatin: behavioral, structural an d biochemical analysis[J]. Auton Neurosci, 2000,86(1-2):84-93.
    [55]Tredici G, Braga M, Nicolini G, et al. Effect of recombinant human nerve growth factor on cisplatin neurotoxicity in rats[J]. Exp Neurol,1999, 159(2):551-558.
    [56]Lanbiase A, Centofanti M, Micera A, et al. Nerve growth factor (NGF) reduces and NGF antibody exacerbates the retinal damage induced in rabbit by experimental ocular hypertension[J]. Grafes Arch Clin Exp Ophthalmol, 1997,235(12):780-785.
    [57]de Santis S, Pace A, Bove L, et al. Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor [J]. Clin Cancer Res,2000,6(1):90-95.
    [58]Cavaletti G, Pezzoni G, Pisano C, et al. Cisplatin-induced peripheral neurotoxicity in rats reduces the circulating levels of nerve growth factor [J]. Neurosci Lett,2002,322(2):103-106.
    [59]李倩,郭伟剑,陈强等.奥沙利铂化疗中血清NGF的动态变化及意义[J].肿瘤,2007,27(6):454-461.
    [60]马艺,王娟,王鑫等.奥沙利铂对大鼠后根神经节及神经生长因子表达的影响[J].实用肿瘤杂志,2005,20(4):293-296.
    [61]司马蕾,贾立群,于莉莉等.奥沙利铂慢性神经毒性对背根神经节尼氏体及P物质的影响[J].药物不良反应杂志,2007,9(5):320-323.
    [62]段小芳.护理干预对减缓奥沙利铂化疗后毒副作用的体会[J].湖南中医杂志,2005,21(3):107-108.
    [63]黄婷,范淑群,汤梅枫等.希罗达化疗反应的护理[J].天津护理杂志,2004,12(6):339.
    [64]Maindrault-Goebel F, Louver C, Carola E, et al. Oxaliplatin reintroduction in patients pretreated with leucovorin(LV),5-Fu and oxaliplatin for metastatic colorectal cancer. a gercor study[J]. Proc Am Soc Clin Oncol, 2000,19:255a.
    [65]Jamieson SM, Liu J, Hsu T, et al. Paclitaxel induces nucleolar enlargement in dorsal root ganglion neurons in vivo reducing oxaliplatin toxicity[J]. Br J Cancer,2003,88(12):1942-1947.
    [66]Gamelin L,Boisdron CM,Delva R,et al. A retrospective study of 161 patients receiving oxaliplatin combined with 5-fluorouracil and leucovorin for advanced colorectal cancer [J]. Clin Cancer Res,2004,10:4055-4061.
    [67]何敬东,岳顺,陈小飞等.草酸铂神经毒性的防治[J].中国肿瘤临床与康复,2004,11(4):324-325.
    [68]郑宇,潘宏铭,楼海舟等.硫酸镁预防奥沙利铂神经毒性的临床观察[J].实用肿瘤杂志,2004,19(2):154-155.
    [69]Eckel F, Schmelz R, Adelsberger H, et al. Prevention of oxaliplatin-induced neuropathy by carbamazepine. A pilot Study[J]. Dtseh Med Wochenschr, 2002,127(3):78-82.
    [70]Cersosimo RJ, Oxaliplatin -associated neuropathy:a review [J]. Ann Pharmacother,2005,39:128-135.
    [71]Mariani G, Garronne O, Granetto C, et al. Oxaliplatin induced neuropathy: Could gabapentin be the answer[J]. Proc Am Soc Clin Ontol,2000,19: 609a.
    [72]Flatters SJ, Bennett GJ. Ethosuximide reverses paclitaxel and vincristine induced painful peripheral neuropathy[J]. Pain,2004,109(1-2):150-161.
    [73]Cascinu S, Catalano V, Cordella L, et al. Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer:a randomized, double-blind, placebo-controlled trial [J]. JClin Oncol,2002,20:3478-3483.
    [74]Park SA, Choi KS, Bang JH, et al. Cisplatin-induced apoptotic cell death in mouse hybrid neurons is blocked by antioxidants through suppression of cisplatin-mediated accumulation of p53 but not of Fas/Fas ligand[J]. J Neurochem,2000,75:946-953.
    [75]Caxciru S, Catalano V, Cordella L, et al. Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer:a randomized, double-blind, placebo-controlled trial [J]. Clin Oncol,2002,20:478-483.
    [76]陈庆丰,马爱英,王海沽.谷胱甘肽对奥沙利铂神经毒性的防治效果[J].东南国防医药,2004,6:257-258.
    [77]王颖杰,张文霞,陈友山.谷胱甘肽对长春地辛周围神经毒性防治作用的初步研究[J].实用癌症杂志.2008.23(1):79-82.
    [78]杨渤彦,王雅茹,王志宇等.三磷酸胞苷二钠防治草酸铂外周神经毒性的临床观察[J].实用肿瘤杂志,2004,19:236-238.
    [79]Gedlicka C, Scheithauer W, Schull B, et al. Effective treatment of oxaliplatin-induced cumulative polyneuropathy with alpha-lipoic Acid[J]. J Clin Oncol,2002,20(15):3359-3361.
    [80]江素华,黄慧,曾渡航.爱维治预防希罗达引起的黏膜损伤和手足综合征的临床观察[J].南方医科大学学报,2008,28(11):2049-2050.
    [81]Bardos G, Moricz K, Jaszlits L, et al. BGP-15, a hydroximic acid-derivative, protects against cisplatin or taxol-induced peripheral neuropathy in rats[J]. Toxicol Appl Pharmacol,2003,190(1):9-16.
    [82]徐国启,胡燕,郭丽娟等.维生素B1和B12治疗草酸铂神经毒性34例临床观察[J].中国肿瘤临床与康复.2004.11(6):554.
    [83]Argyriou AA, Chroni E, Koutras A, et al. Vitamin E for prophylaxis against chemotherapy induced neuropathy:a randomized controlledtrial[J]. Neurology,2005 Jan 11,64(1):26-31.
    [84]陈文晟,刘晓燕,金川.大剂量维生素B6预防卡培他滨所至手足综合征的疗效分析[J].广西医学,2009,31(1):61-62.
    [85]Wilson RH, Lehky T, Thomas RR, et al. Acute oxaliplatin-induced peripheral nerve hyperexcitability[J]. J Clin Oncol,2002,20(7):1767-1774.
    [86]Lin E, Morris JS,Ayers GD. Effect of celecoxib on capecitabin-induced hand-foot syndrome and antitumor activity[J]. Oncology(Williston Park),2002,16:31-37.

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