抗肿瘤药卡莫司汀临床应用进展
Progress in Clinical Application of Carmustine
DOI: 10.12677/HJMCe.2018.64014, PDF,  被引量    科研立项经费支持
作者: 陈 鑫, 吴飞跃, 黄孟军, 罗 燕*：重庆文理学院材料与化工学院，重庆
关键词: 卡莫司汀；抗肿瘤；临床应用；药物联用；Carmustine； Antitumor； Clinical Application； Drug Combination
摘要: 恶性肿瘤的治疗仍然是当今世界难以攻克的难题，目前主要的治疗方法是手术切除加术后化疗。卡莫司汀是40多年前应用于临床的广谱抗癌药，也是应用在胶质瘤化疗中最广泛的药物。本文综述了卡莫司汀的作用机理及近年来在临床方面的一些应用与突破。
Abstract: The treatment of malignant tumors is still a difficult problem in the world today. The main treat-ment methods are surgical resection and postoperative chemotherapy. Carmustine is a broad-spectrum anticancer drug that has been used clinically for more than 40 years. It is also the most widely used drug in glioma chemotherapy. This article reviews the mechanism of action of carmustine and some clinical applications and breakthroughs in recent years.
文章引用：陈鑫, 吴飞跃, 黄孟军, 罗燕. 抗肿瘤药卡莫司汀临床应用进展[J]. 药物化学, 2018, 6(4): 97-105. https://doi.org/10.12677/HJMCe.2018.64014

参考文献

[1] Bota, D.A., Desjardins, A., Quinn, J.A., Affronti, M.L. and Friedman, H.S. (2007) Interstitial Chemotherapy with Biodegradable BCNU (Gliadel®) Wafers in the Treatment of Malignant Gliomas. Therapeutics & Clinical Risk Management, 3, 707-715.
[2] 唐慰慈. 亚硝基脲类抗癌药物[J]. 药学学报, 1982, 17(6): 472-479.
[3] Ueda-Kawamitsu, H., Lawson, T.A. and Gwilt, P.R. (2002) In Vitro Pharmacokinetics and Pharmacodynamics of 1,3-Bis(2-chloroethyl)-nitrosourea (BCNU). Biochemical Pharmacology, 63, 1209-1218. [Google Scholar] [CrossRef] 
[4] Penketh, P.G., Shyam, K. and Sartorelli, A.C. (2000) Comparison of DNA Lesions Produced by Tumor Inhibitory 1,2-Bis(sulfonyl)hydrazines and Chloroethylnitrosoureas. Biochemical Pharmacology, 59, 283-291. [Google Scholar] [CrossRef] 
[5] Engelhard, H.H. (2000) The Role of Interstitial BCNU Chemotherapy in the Treatment of Malignant Glioma. Surgical Neurology, 53, 458-464. [Google Scholar] [CrossRef] 
[6] 章文斌, 马晓东, 周定标. BCNU缓释制剂的研究进展[J]. 中国微侵袭神经外科杂志, 2005, 10(4): 189-192.
[7] Tamargo, R.J., Myseros, J.S., Epstein, J.I., Yang, M.B., Chasin, M. and Brem, H. (1993) Interstitial Chemotherapy of the 9L Gliosarcoma: Controlled Release Polymers for Drug Delivery in the Brain. Cancer Research, 53, 329-333.
[8] Domb, A.J., Israel, Z.H., Elmalak, O., Teomim, D. and Bentolila, A. (1999) Preparation and Characterization of Carmustine Loaded Polyanhydride Wafers for Treating Brain Tumors. Pharmaceutical Research, 16, 762-765. [Google Scholar] [CrossRef] 
[9] Pereira, D.Y., Yip, A.T., Lee, B.S. and Kamei, D.T. (2014) Modeling Mass Transfer from Carmustine-Loaded Polymeric Implants for Malignant Gliomas.Journal of Laboratory Automation, 19, 19-34. [Google Scholar] [CrossRef] [PubMed]
[10] Kleinberg, L. (2016) Polifeprosan 20, 3.85% Carmustine Slow Release Wafer in Malignant Glioma: Patient Selection and Perspectives on a Low-Burden Therapy. Patient Preference and Adherence, 10, 2397-2406. [Google Scholar] [CrossRef] 
[11] Shive, M.S. and Anderson, J.M. (2012) Biodegradation and Biocompatibility of PLA and PLGA Microspheres. Advanced Drug Delivery Reviews, 64, 5-24.
[12] Lee, J.S., An, T.K., Chae, G.S., Jeong, J.K., Cho, S.H., Lee, H.B. and Khang, G. (2005) Evaluation of In Vitro and In Vivo Antitumor Activity of BCNU-Loaded PLGA Wafer against 9L Gliosarcoma. European Journal of Pharmaceutics & Biopharmaceutics, 59, 169-175. [Google Scholar] [CrossRef] [PubMed]
[13] Zhu, T.M., Shen, Y.W., Tang, Q.S., Chen, L.P., Gao, H.S. and Zhu, J.H. (2014) BCNU/PLGA Microspheres: A Promising Strategy for the Treatment of Gliomas in Mice. Chinese Journalof Cancer Research, 26, 81-88.
[14] Xu, X., Chen, X., Xu, X., Lu, T., Wang, X., Yang, L. and Jing, X. (2006) BCNU-Loaded PEG-PLLA Ultrafine Fibers and Their In Vitro Antitumor Activity against Glioma C6 Cells. Journal of Controlled Release, 114, 307-316. [Google Scholar] [CrossRef] [PubMed]
[15] Lu, Y.J., Yang, H.W., Hung, S.C., Huang, C.Y., Li, S.M., Ma, C.C., Chen, P.Y., Tsai, H.C., Wei, K.C. and Chen, J.P. (2012) Improving Thermal Stability and Efficacy of BCNU in Treating Glioma Cells Using PAA-Functionalized Graphene Oxide. International Journal of Nanomedicine, 7, 1737-1747.
[16] Kim, M.S., Seo, K.S., Seong, H.S., Cho, S.H., Lee, H.B., Hong, K.D., Kim, S.K. and Khang, G. (2005) Synthesis and Characterization of Polyanhydride for Local BCNU Delivery Carriers. Bio-Medical Materials and Engineering, 15, 229-238.
[17] Li, Y., Ho Duc, H.L., Tyler, B., Williams, T., Tupper, M., Langer, R., Brem, H. and Cima, M.J. (2005) In Vivo Delivery of BCNU from a MEMS Device to a Tumor Model. Journal of Controlled Release, 106, 138-145. [Google Scholar] [CrossRef] [PubMed]
[18] Alexandru, D., Linskey, M.E., Kim, R.C. and Bota, D.A. (2013) Undifferen-tiated Sarcoma Induced by BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) Wafers. Journal of Interdisciplinary Histopathology, 1, 163-167. [Google Scholar] [CrossRef] 
[19] Sukumari-Ramesh, S., Prasad, N., Alleyne Jr., C.H., Vender, J.R. and Dhandapani, K.M. (2015) Overexpression of Nrf2 Attenuates Carmustine-Induced Cytotoxicity in U87MG Human Glioma Cells. BMC Cancer, 15, 118-127. [Google Scholar] [CrossRef] [PubMed]
[20] Figueiredo, E.G., Faria, J.W. and Teixeira, M.J. (2010) Treatment of Recurrent Glioblastoma with Intra-Arterial BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea]. Arquivos de Neuro-Psiquiatria, 68, 778-782. [Google Scholar] [CrossRef] 
[21] Reithmeier, T., Graf, E., Piroth, T., Trippel, M., Pinsker, M.O. and Nikkhah, G. (2010) BCNU for Recurrent Glioblastoma Multiforme: Efficacy, Toxicity and Prognostic Factors. BMC Cancer, 10, 30-36. [Google Scholar] [CrossRef] [PubMed]
[22] Jungk, C., Chatziaslanidou, D., Ahmadi, R., Capper, D., Bermejo, J.L., Exner, J., von Deimling, A., Herold-Mende, C. and Unterberg, A. (2016) Chemotherapy with BCNU in Recurrent Glioma: Analysis of Clinical Outcome and Side Effects in Chemotherapy-Naïve Patients. BMC Cancer, 16, 81-91. [Google Scholar] [CrossRef] [PubMed]
[23] Ene, C.I., Nerva, J.D., Morton, R.P., Barkley, A.S., Barber, J.K., Ko, A.L. and Silbergeld, D.L. (2016) Safety and Efficacy of Carmustine (BCNU) Wafers for Metastatic Brain Tumors. Surgical Neurology Inter-national, 7, S295-S299. [Google Scholar] [CrossRef] [PubMed]
[24] Zackheim, H.S. (2003) Topical Carmustine (BCNU) in the Treatment of Mycosis Fungoides. Dermatologic Therapy, 16, 299-302. [Google Scholar] [CrossRef] [PubMed]
[25] MacArthur, K.M., Jariwala, N., Kim, E.J. and Rook, A.H. (2017) Topical Carmustine as Monotherapy or as Multimodality Therapy for Folliculotropic Mycosis Fungoides. Acta Dermato-Venereologica, 97, 373-374. [Google Scholar] [CrossRef] [PubMed]
[26] 高玉杰. 卡莫司汀及全脑预防照射对缓解期小细胞肺癌脑转移预防作用的疗效观察及预后相关性分析[D]: [硕士学位论文]. 大连: 大连医科大学, 2013.
[27] Mokhtari, R.B., Homayouni, T.S., Baluch, N., Morgatskaya, E., Kumar, S., Das, B. and Yeger, H. (2017) Combination Therapy in Combating Cancer. Oncotarget, 8, 38022-38043. [Google Scholar] [CrossRef] [PubMed]
[28] Vogelhuber, W., Spruss, T., Bernhardt, G., Buschauer, A. and Göpferich, A. (2002) Efficacy of BCNU and Paclitaxel Loaded Subcutaneous Implants in the Interstitial Chemotherapy of U-87 MG Human Glioblastoma Xenografts. International Journal of Pharmaceutics, 238, 111-121. [Google Scholar] [CrossRef] 
[29] Lonser, R.R., Sarntinoranont, M., Morrison, P.F. and Oldfield, E.H. (2015) Convection-Enhanced Delivery to the Central Nervous System. Journal of Neurosurgery, 122, 697-706. [Google Scholar] [CrossRef] 
[30] Zhan, W., Arifin, D.Y., Lee, T.K. and Wang, C.H. (2017) Mathematical Mod-elling of Convection Enhanced Delivery of Carmustine and Paclitaxel for Brain Tumour Therapy. Pharmaceutical Research, 34, 860-873. [Google Scholar] [CrossRef] [PubMed]
[31] Thamilselvan, V., Menon, M. and Thamilselvan, S. (2016) Combination of Carmustine and Selenite Effectively Inhibits Tumor Growth by Targeting Androgen Receptor, Androgen Receptor-Variants, and Akt in Preclinical Models: New Hope for Patients with Castration Resistant Prostate Cancer. International Journal of Cancer, 139, 1632-1647. [Google Scholar] [CrossRef] [PubMed]
[32] Thamilselvan, V., Menon, M., Stein, G.S., Valeriote, F. and Thamilselvan, S. (2017) Combination of Carmustine and Selenite Inhibits EGFR Mediated Growth Signaling in Androgen-Independent Prostate Cancer Cells. Journal of Cellular Biochemistry, 118, 4331-4340. [Google Scholar] [CrossRef] [PubMed]
[33] Azzalin, A., Nato, G., Parmigiani, E., Garello, F., Buffo, A. and Magrassi, L. (2017) Inhibitors of GLUT/SLC2A Enhance the Action of BCNU and Temozolomide against High-Grade Gliomas. Neoplasia, 19, 364-373. [Google Scholar] [CrossRef] [PubMed]
[34] Krishnan, A.Y., Palmer, J., Nademanee, A.P., Chen, R., Popplewell, L.L., Tsai, N.C., Sanchez, J.F., Simpson, J., Spielberger, R. and Yamauchi, D. (2017) Phase II Study of Yttrium-90 Ibritumomab Tiuxetan plus High-Dose BCNU, Etoposide, Cytarabine, and Melphalan for Non-Hodgkin Lymphoma: The Role of Histology. Biology of Blood and Marrow Transplantation, 23, 922-929. [Google Scholar] [CrossRef] [PubMed]
[35] 孔庆忠, 张红军. 一种同载卡莫司汀和氟尿嘧啶的抗癌缓释剂[P]. CN: 2007.CN100998558A.