抗肿瘤药物临床超常用药分析

Analysis of Abnormal Use of Anti-tumor Drugs in the Clinic

目的:研究抗肿瘤药物临床超常用药的情况,为其临床合理用药提供参考。方法:参考国内外抗肿瘤药物应用指南及相关文献、《新型抗肿瘤药物临床应用指导原则(2018年版)》《超药品说明书用药目录(2019版)》《实用肿瘤内科学》(第2版)、美国食品药品监督管理局(FDA)批准的抗肿瘤药品说明书以及国内已上市的抗肿瘤药品说明书等资料,对抗肿瘤药物超常用药(包括超说明书用法、特殊适应证用法、新型抗肿瘤药物联用时给药顺序)进行归纳整理及分析。结果与结论:抗肿瘤药物超说明书用药共有4项,涉及11个品种,如超用药方案(重组人血管内皮抑制素、利妥昔单抗)、超给药途径(培美曲塞二钠、硼替佐米、贝伐珠单抗)、超治疗线数(厄洛替尼、吉非替尼)、超给药剂量(放线菌素D、吉西他滨、异环磷酰胺、依托泊苷),临床使用中应谨慎选用、严格监控,根据需要调整治疗方案。特殊适应证用法中涉及环磷酰胺、阿糖胞苷、甲氨蝶呤和顺铂4种药物的大剂量用法,剂量分别为2 000~2 400 mg/m^2、2 000 mg/m^2、12 g/m^2、80~120 mg/m^2,临床使用中应注意个体差异,必要时进行治疗药物监测。新型抗肿瘤药物之间联用或与传统化疗药物联合用药方案中,共涉及5类共11项,包括分子靶向抗肿瘤药物联用传统化疗药物(如先用多西他赛,同时或之后用吉非替尼)、靶向免疫检查点药物联用传统化疗药物(如先用铂类再用纳武利尤单抗)、分子靶向抗肿瘤药物间的相互联用(如帕妥珠单抗和曲妥珠单抗须序贯给药,但先后顺序均可)等,临床使用中应明确患者的病理组织学诊断,对有明确靶点的药物须进行基因检测后再使用并严格遵循适应证用药。

OBJECTIVE:To study the abnormal use of anti-tumor drugs in the clinic in order to provide reference for rational use of drugs in the clinic.METHODS:Referring to foreign and domestic anti-tumor drug use guidelines and literatures,Guidelines for Clinical Use of New Anti-tumor Drugs(2018 edition),Off-label Drug Use List(2019 edition),Practical Oncology(secondary edition),anti-tumor drug package inserts approved by FDA and package inserts of anti-tumor drug listed in China,abnormal use of antitumor drugs(including instructions,special indications,and the order of administration of new anti-tumor drugs)was summarized and analyzed.RESULTS&CONCLUSIONS:The off-label use of anti-tumor drugs were summarized in this paper,including 11 drug varieties and 4 kinds of off-label drug items,such as off-label drug use plan(recombinant human endostatin,rituximab),off-label administration route(pemetrexed disodium,bortezomib,bevacizumab),off-label administration lines(erlotinib,gefitinib),off-label drug dosage(actinomycin D,gemcitabine,ifosfamide,etoposide).They should be carefully selected and strictly monitored in clinical use,and treatment plan should be adjusted according to needs.Among the special indications,cyclophosphamide,cytarabine,methotrexate and cisplatin were used in large doses,which were 2000-2400 mg/m^2,2000 mg/m^2,12 g/m^2 and 80-120 mg/m^2,respectively;individual differences should be paid attention to and therapeutic drug monitoring should be carried out if necessary.In the scheme of combination of new anti-tumor drugs or traditional chemotherapy drugs,there were 5 categories and 11 items in total,such as combination of molecular targeted anti-tumor drugs with traditional chemotherapy drugs(such as docetaxel at first,gefitinib at the same time or later),combination of target immunocheckpoint drugs with traditional chemotherapy drugs(such as platinum at first,then nivolumab),and molecular targeted anti-tumor drugs combination(such as pertuzumab and trastuzumab should be given in sequence,in either order).In clinical use,histopathological diagnosis should be made clear,and drugs with specific targets should be used after gene detection and strictly follow the indications.