肺结核与肺癌共病诊疗专家共识

doi:10.19982/j.issn.1000-6621.20250276

摘要/Abstract

摘要：

肺结核与肺癌共病是指同一患者同时或先后罹患肺结核与肺癌两种疾病的状态。肺结核与肺癌共病的发生增加了诊断与鉴别诊断难度,易造成漏诊、误诊及治疗延迟。肺癌化疗、靶向药物与抗结核药物间存在复杂的相互作用,不仅影响抗结核和抗肿瘤的疗效,还显著增加药物的不良反应,亟需通过多学科协作,制定规范化诊疗共识,指导临床实践。为此,中国防痨协会多学科诊疗分会与国家感染性疾病临床医学研究中心(深圳市第三人民医院)共同牵头,联合首都医科大学附属北京朝阳医院、广东省肺癌研究所等,制定了《肺结核与肺癌共病诊疗专家共识》。本共识对肺结核与肺癌共病的流行病学特征、临床表现、诊断与治疗,以及结核分枝杆菌潜伏感染筛查与管理进行了阐述,重点围绕药物相互作用、治疗方案调整、手术与放疗时机把握等临床难点问题提出了解决方案,共提出了22条推荐意见,以期为临床实践提供规范化指引。

关键词: 结核,肺, 肺肿瘤, 共病现象, 诊断, 治疗应用

Abstract:

Comorbidity of pulmonary tuberculosis and lung cancer refers to the condition where the same patient is affected by both pulmonary tuberculosis and lung cancer either simultaneously or sequentially. The occurrence of such comorbidity increases the difficulty in diagnosis and differential diagnosis, easily resulting in missed diagnoses, misdiagnoses, and delayed treatment. There exist complex interactions between lung cancer chemotherapy, targeted drugs, and anti-tuberculosis drugs, which not only impair the efficacy of anti-tuberculosis and anti-tumor treatments but also significantly elevate adverse drug reactions. Hence, there is an urgent need to develop standardized diagnosis and treatment consensus through multidisciplinary collaboration to guide clinical practice. The Multidisciplinary Diagnosis and Treatment Branch of Chinese Antituberculosis Association and the National Clinical Research Center for Infectious Diseases/Shenzhen Third People’s Hospital, in collaboration with Beijing Chao-Yang Hospital, Capital Medical University, Guangdong Lung Cancer Institute and other institutions, have jointly developed the Expert consensus on the diagnosis and treatment of coexistent pulmonary tuberculosis and lung cancer. This consensus elaborates on the epidemiological characteristics, clinical manifestations, diagnosis, and treatment of pulmonary tuberculosis-lung cancer comorbidity. It also addresses the screening and management of latent tuberculosis infection. Special emphasis is placed on key clinical challenges, such as drug-drug interactions, optimization of treatment regimens, and the appropriate timing of surgery and radiotherapy. The consensus provides 22 specific recommendations to support standardized and evidence-based clinical decision-making.

Key words: Tuberculosis, pulmonary, Lung neoplasms, Comorbidity, Diagnosis, Therapeutic uses

中图分类号:

R52
R734.2

中国防痨协会多学科诊疗分会, 深圳市第三人民医院(国家感染性疾病临床医学研究中心), 首都医科大学附属北京朝阳医院, 广东省肺癌研究所. 肺结核与肺癌共病诊疗专家共识[J]. 中国防痨杂志, 2025, 47(9): 1105-1125. doi: 10.19982/j.issn.1000-6621.20250276

Multidisciplinary Diagnosis and Treatment Branch of Chinese Antituberculosis Association , National Clinical Research Center for Infectious Disease/Shenzhen Third People’s Hospital , Beijing Chao-Yang Hospital, Capital Medical University , Guangdong Lung Cancer Institute . Expert consensus on the diagnosis and treatment of coexistent pulmonary tuberculosis and lung cancer[J]. Chinese Journal of Antituberculosis, 2025, 47(9): 1105-1125. doi: 10.19982/j.issn.1000-6621.20250276

图/表 4

图1~12

图13~20

表1

肺癌化疗相关药物与利福平相互作用及使用建议

药品	药物代谢酶	与利福平相互作用	建议
紫杉醇类(含紫杉醇、紫杉醇脂质体、白蛋白紫杉醇、紫杉醇胶束)	CYP3A4/2C8	利福平诱导CYP3A4,加速紫杉醇类药物代谢,降低血药浓度,药品说明书建议谨慎合用	A
多西他赛	CYP3A4/2C8	利福平诱导CYP3A4,导致多西他赛清除率增加,血药浓度下降。药品说明书建议谨慎合用	A
顺铂/卡铂	非CYP代谢	铂类药物通过DNA交联发挥作用,不依赖CYP酶代谢。药品说明书建议使用利福平无需调整剂量	C
培美曲塞	非CYP代谢	培美曲塞主要经肾排泄,利福平不影响其清除率。药品说明书建议无需调整剂量	C
吉西他滨	非CYP代谢	吉西他滨通过胞嘧啶脱氨酶代谢,利福平不影响该酶活性。药品说明书建议无需调整剂量	C
依托泊苷	CYP3A4	利福平可能诱导CYP3A4,加速依托泊苷代谢,增加骨髓抑制风险。药品说明书建议谨慎合用	A
伊立替康	CYP3A4	利福平诱导CYP3A4,增加伊立替康活性代谢产物SN-38生成,可能加重腹泻毒性。药品说明书建议谨慎合用	A
长春瑞滨	CYP3A4	利福平诱导CYP3A4,可能降低长春瑞滨血药浓度。药品说明书建议谨慎合用	A
替莫唑胺	非酶水解	替莫唑胺在酸性条件下水解为活性产物,利福平不影响其分解过程。药品说明书建议无需调整剂量	C
芦比替定	CYP3A4	芦比替定主要经CYP3A4代谢,利福平诱导酶活性可能降低其疗效。药品说明书建议尽量避免使用	A
芦康沙妥珠单抗	TROP2抗体部分不依赖CYP代谢,细胞毒性部分(KL610023,拓扑异构酶Ⅰ抑制剂)由CYP3A4代谢	尚缺乏患者体内相互作用研究,但理论上利福平可能会削弱芦康沙妥珠单抗的疗效,建议谨慎合用	B
德曲妥珠单抗	HER2抗体部分不依赖CYP代谢,细胞毒性部分(DXd,拓扑异构酶Ⅰ抑制剂)主要由CYP3A4代谢	尚缺乏患者体内相互作用研究,但理论上利福平可能会削弱德曲妥珠单抗的疗效,建议谨慎合用	B

表1

表2

肺癌常用靶向治疗药物与利福平相互作用及使用建议

药品	作用靶点	药物代谢酶	与利福平相互作用及底物AUC变化	建议
奥希替尼	EGFR	CYP3A4	说明书提示利福平诱导CYP3A4会显著降低其血药浓度。使奥希替尼的稳态AUC下降78%^[62]。药品说明书建议避免合用或增加剂量	A
阿美替尼	EGFR	CYP3A4	说明书提示阿美替尼与利福平联用会导致暴露量显著降低(AUC降低约90%)。药品说明书建议谨慎合用	A
伏美替尼	EGFR	CYP3A4	伏美替尼与强诱导剂或抑制剂联合使用时需谨慎。药品说明书建议谨慎合用	B
贝福替尼	EGFR	CYP3A4	与强诱导剂合并使用可能会导致本品血药浓度降低。药品说明书建议谨慎合用	B
阿法替尼	EGFR、HER2	P-gp	利福平为P-gp诱导剂。上市后研究表明:利福平连续7d,可将阿法替尼的血浆暴露量降低33.8%(AUC)和21.6%(药峰浓度)^[58]。药品说明书建议避免合用或增加剂量	B
达可替尼	EGFR	CYP2D6、CYP3A4	说明书提示利福平作为强CYP3A4诱导剂,合用会导致AUC降低80%,导致治疗失败。药品说明书禁止联用	A
吉非替尼	EGFR	CYP3A4	与CYP3A4强诱导剂利福平合用,吉非替尼的平均AUC比单服时降低83%^[63]。药品说明书建议避免合用或增加剂量	A
厄洛替尼	EGFR	CYP3A4、CYP1A2	说明书提示与CYP3A4强诱导剂利福平合用,导致厄洛替尼的平均AUC降低69%^[64]。药品说明书建议避免合用或增加剂量	A
埃克替尼	EGFR	CYP2C19、CYP3A4	与利福平合用,导致暴露量显著降低。药品说明书建议注意避免潜在的药物相互作用	A
利厄替尼	EGFR	CYP3A4	与利福平合用,导致暴露量显著降低。药品说明书建议避免合用	A
瑞厄替尼	EGFR	CYP3A4	利福平加速代谢,显著减少药物暴露量^[65]。药品说明书建议避免合用	A
瑞齐替尼	EGFR	CYP3A4、CYP2B6 CYP2C8、CYP2C9 CYP2C19、CYP2D6	利福平诱导代谢酶,导致血药浓度下降。药品说明书建议避免合用	A
阿来替尼	ALK	CYP3A4	利福平合并用药对阿来替尼的总暴露量的影响较小^[60]。药品说明书建议谨慎合用	B
布格替尼	ALK	CYP2C8、CYP3A4	说明书提示利福平合并使用,可使布格替尼的AUC降低80%^[66]。药品说明书建议避免合用	A
洛拉替尼	ALK	CYP3A4	说明书提示本品禁用于正在服用强效CYP3A诱导剂的患者。利福平使洛拉替尼AUC平均值下降85%^[67]。药品说明书建议避免合用	A
恩沙替尼	ALK	CYP3A4	与强诱导剂联合使用可能会导致本品血药浓度降低。慎用利福平。药品说明书建议谨慎合用	B
伊鲁阿克	ALK	CYP3A4	伊鲁阿克尚未完成与CYP3A4抑制剂和诱导剂联用的药物-药物相互作用研究。与利福平合用可能会导致伊鲁阿克血药浓度的降低	A
塞瑞替尼	ALK	CYP3A4、P-gp	与强效诱导剂利福平联用可显著降低本品的血浆浓度。药品说明书建议避免合用	B
克唑替尼	ALK、ROS1、MET	CYP3A4	说明书提示利福平合并服用时,克唑替尼的稳态AUC_0-Tau降低84%^[68]。药品说明书建议避免合用	A
依奉阿克	ALK、ROS1、MET	CYP3A4	利福平显著降低依奉阿克药物浓度。药品说明书建议避免合用	A
安奈克替尼	ALK、ROS1、c-Met	CYP3A4	与CYP3A4强诱导剂合用会导致血药浓度降低。药品说明书建议避免合用	A
达拉非尼+ 曲美替尼	BRAFV600 MEK1/2	CYP2C8、CYP3A4	说明书提示本身是CYP3A4诱导剂,利福平增强CYP3A4活性,显著降低达拉非尼浓度,AUC下降34%;药品说明书建议避免合用。曲美替尼与利福平无明显相互作用;药品说明书建议可以合用	达拉菲尼B; 曲美替尼C
恩曲替尼	NTRK、ROS1	CYP3A4	说明书提示与强诱导剂利福平合用,可使恩曲替尼的全身暴露量下降77%^[69]。药品说明书建议避免合用	A
拉罗替尼	NTRK	CYP3A4	说明书提示利福平诱导CYP3A4会显著降低其血药浓度(AUC降低81%)。药品说明书建议避免合用	A
瑞普替尼	ROS1、NTRK	CYP3A4/5	强效诱导剂利福平显著降低其血药浓度。药品说明书建议避免合用	A
他雷替尼	ROS1、NTRK	CYP3A4、CYP2D6、 CYP2C8	说明书提示与强诱导剂利福平合用,AUC_inf降低86%。药品说明书建议避免合用	A
谷美替尼	MET	CYP3A4	CYP3A4为谷美替尼的主要代谢酶,但其对其代谢贡献有限(<5%),提示CYP抑制剂或诱导剂不太可能与临床剂量的谷美替尼发生相互作用。药品说明书建议无需调整剂量	C
伯瑞替尼	MET	CYP3A4、CYP2C9	伯瑞替尼可通过多种代谢酶代谢,但主要通过CYP3A4代谢。说明书提示与强诱导剂利福平合用,可使伯瑞替尼的AUC下降65%。药品说明书建议避免合用	A
特泊替尼	MET	CYP3A4、P-gp	强效P-gp诱导剂可能会降低特泊替尼的暴露量。强效CYP诱导剂也可能会降低特泊替尼的暴露量。药品说明书建议避免合用	A
赛沃替尼	MET	CYP1A2、CYP3A4、 CYP3A5	说明书提示与利福平合用会使赛沃替尼AUC降低61%^[70]。药品说明书建议避免合用	A
卡马替尼	MET	CYP3A4	利福平诱导CYP3A4会显著降低其血药浓度。药品说明书建议避免合用或增加剂量	A
氟泽雷塞	KRAS G12C	谷胱甘肽S-转移酶	氟泽雷赛的主要代谢途径为谷胱甘肽S-转移酶介导的半胱氨酸结合,其对CYP3A4既有潜在抑制作用,也有潜在诱导作用。药品说明书建议可以合用	C
格索雷塞	KRAS G12C	CYP3A4、CYP2C8	利福平显著降低药物暴露量。药品说明书建议避免合用	A
塞普替尼	RET	CYP3A4	说明书提示利福平强效诱导CYP3A4会降低其血药浓度,AUC下降87%。药品说明书建议避免合用	A
普拉替尼	RET	CYP3A4、CYP2D6、 CYP1A2	说明书提示强效CYP3A抑制剂避免与强效CYP3A抑制剂联合用药,AUC下降68%。药品说明书建议避免合用	A
埃万妥单抗	EGFR、MET	网状内皮系统降解	尚未开展药物相互作用研究	B
贝伐珠单抗	VEGF-A	蛋白水解分解代谢	与利福平无药代动力学相互作用。药品说明书建议可以合用	C
重组人血管内皮抑素	VEGFR2、MMP、 lntegrin等	通过蛋白水解代谢	与利福平合用未见报道。说明书中无具体提及。根据生物药品特征,其对CYP3A4酶的影响不大,故与利福平合用风险小	C
依沃西单抗	VEGF-A、PD-1	网状内皮系统降解	与利福平合用未见相互作用报道。药品说明书建议可以合用	C
安罗替尼	VEGFR1-3、FGFR、 PDGFR等	CYP1A2、 CYP3A4/5	CYP3A4/5诱导剂(利福平、利福布汀、利福喷丁等)可能加速安罗替尼的代谢,降低安罗替尼的血浆浓度。药品说明书建议避免合用	A

表2

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