恶性肿瘤的药物治疗 (总论) 1931 Department of Pharmacy Fudan University Shanghai Cancer Center A复旦大学附属肿瘤医院 翟青 Fudan University Shanghai Cancer Center 2017年12月6日
翟青 2017年12月6日 恶性肿瘤的药物治疗 （总论）
药剂科 简介 回aa Established since 1931 □百吸区 □ 万级区 □+万继 12 Multidisciplinary Management Teams; 人方 1189 Clinical Staffs: 80 Pharmacists: >3 Clean Room 1196 Beds; 8 Biological safety cabinets; 34,000 Inpatients; -800,000 Outpatients; 6 Horizontal Laminar Airflow Cabinets; 70, 000 Chemo Cases; 800 Chemo/Day max
简介 • Established since 1931; • 12 Multidisciplinary Management Teams; • 1189 Clinical Staffs; • ~80 Pharmacists; • 1196 Beds； • ~34, 000 Inpatients; ~800, 000 Outpatients; • ~70, 000 Chemo Cases; ~800 Chemo/Day max; ➢ 3 Clean Room; ➢ 8 Biological safety cabinets; ➢ 6 Horizontal Laminar Airflow Cabinets; 2
药剂科 Contents ·卫生部 分期 规范 其他概论 治疗药物 指南 分类 原则
Contents • 分类 • 原则 • 指南 • 卫生部 • 分期 规范 其他 概论 治疗 药物 3
药剂科 概论 Google; wiki cancer statistics 定义 CAACancerJ Journal for clinici 分类 TNM Staging 流行 The Common Language of Cancer 病学 ANATOMIC STAGE/PROGNOSTIC GROUPS noetIc MO NO M 分期 BTO N1 I Cancer 策 N1 略 Staging g ing stage B Atlas on to the 预 of the AICC Cancer T3 M 后 Staging Manual and SECOND EDITION l Any T
概论 定义 分类 流行 病学 分期 Google; wiki; cancer statistics TNM Staging: The Common Language of Cancer 策 略 预 后 4
药剂科 概论 T2 T4 tension to chest wall ot includi >20-50mm >10-20mm=T1c 二= (>5-10 mm=Tib >1-5 mm=Lay >50mm 中●中中中中丶中中命电中中 mary Tumor TX Primary tumor cannot be assessed n Tumor s 20 mm in greatest dimension T4 Tumor of any size with direct extension to the chest TO No evidence of primary tumor TImi Tumor s 1 mm in greatest dimension wall and/or to the skin (ulceration or skin nodules) Tis Carcinoma in situ Tla Tumor >1 mm but s 5mm in greatest dimension Note: Invasion of the dermis alone does not qualify Tis(DCIS) Ductal carainoma in situ TTb Tumor>5mm but s 10 mm in greatest dimension T4a Extension to the dhest wall, not induding only Tis(LCIS) Lobular caranoma in situ Tlc Tumor >10 mm but s 20 mm in greatest dimension pectoralis musde adherence/invasion Tis(Paget's) Paget, s disease of the nipple NOT assodated with 12 Tumor >20 mm but s 50 mm in greatest dimension T4b Ulceration and/or ipsilateral satellite nodules and/or invasive caranoma and/or cardnoma in stu(DCs 13 Tumor >50 mm in greatest dimension edema (induding peau dorange)of the skin, whidh and/or LaS)in the underlying breast parenchyma. do not meet the criteria for inflammatory caranoma Carcinomas in the breast parenchyma assodated with Paget's disease are categorized based on the T4c Both T4a and T4b size and characteristics of the parenchymal disease, T4d Inflammatory caranoma(see "Rules for Ithough the presence of Paget's disease should stil dassification)
概论 5
药剂科 概论 Supraclavicular pNimi High axillary, apical >0.2-2 mm or more levelⅢ Halsted's than 200 cells ligament Mid-axillary level Axillary vein Low axillary pIla: 1-3 nodes level I (at least one tumor deposit >2.0 mm) pNo(i+ Internal pN2a: 4-9 nodes Pectoralis mammary (at least one tumor minor deposit >2.0 mm) muscle pN3a:≥10node (at least one tumor deposit >2.0 mm) ≤02 mm or cluster of fewer than 200 cells
概论 6
药剂科 概论 ANATOMIC STAGE/PROGNOSTIC GROUPS ●中中●中争●中中●卓中争●中中中争中中争中中中中中争中中中●中中中中中中中中导命中命●中中争●中罪 Distant Metastases (M Stage 0 Tis N MO NO Mo No dinical or radiographic evidence of distant Stage IA metastases Stage IBTO Nlm Mo cMo(i+) No dinical or radiographic evidence of distant Nimi metastases, but deposits of molecularly or Stage IIA TO N1** MO microscopically detected tumor cells in circulating N1 MO blood, bone marrow, or other nonregional nodal MO tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastases Stage lIB MO M1 Distant detectable metastases as determined by T3 NO MO dassic dinical and radiographic means and/or age l N2 MO histologically proven larger than 0.2mm MO MO T3 MO Stage lB NO MO MO StagelIcAnyT N3 MO Stage IV Any T AnyN M1′
概论 7
药剂科 药物 化疔药物的药理机制 嘌呤 嘧啶 抑制核苷酸合成代谢抗代谢类药:吉西他滨、甲氨 核苷酸 蝶呤、5-FU、卡培他滨 干扰DNA复制 烷化剂:环磷酰胺 DNA 拓扑异构酶Ⅰ抑制剂:伊立替康 其他类:铂类化合物 干扰转录过程 RNA 蒽环类:表柔比星 蛋白质 干扰徽管蛋白 酶类微管 抗微管类药:紫杉类、长春碱类 抗雌激素类药:他莫西芬、来曲唑和阿那曲唑 8
药物 8
药剂科 药物 M期(有丝分裂期) 植物药 G2期(RNA微管蛋白 紫杉类,长春碱类 合成期) 博莱霉素 G1期(DNA合成前期) M dnsi Rb dephosphorylation Cel prepares to divide cel grows G1 Cyclin BIA otic CDK1 CDC2 phase whether to of DNA contnue cye周期非特异性药 CDK4.6 物 s期(DNA合成期) 烷化剂 Cyclin A 抗代谢药、植物药 CDK2 抗生素类 5-FU,MIX,培美 Cyclin E Rb CDK2 phosphorylatio 曲塞,喜树碱类 铂类
G2期（RNA/微管蛋白 合成期） 博莱霉素 周期非特异性药 物 烷化剂 抗生素类 铂类 S期（DNA合成期） 抗代谢药、植物药 5-FU，MTX，培美 曲塞，喜树碱类 M期（有丝分裂期） 植物药 紫杉类，长春碱类 G1期（DNA合成前期） 药物
药剂科 药物 烷化剂/ Alkylating agents 常见方案? >非周期特异/ Not cel- cycle specific; 代表药物 毒性依赖于微粒体酶系活性 环磷酰胺/( Cyclophosphamide(CTX) 苯丁酸氮芥(留可然)/ Chlorambucil( Leukeran) 亚硝基脲/ nitrosoureas(BNCU,CCNU) 耐药性/ Resistance 不可使用GSH保肝 Increased ability to repair dna defects Decreased cellular permeability to the drug Increased glutathione synthesis:被GST失活 主要毒性/ Toxicity(main ANC1500?/PLT100? 性腺;消化道/GI;骨髓抑制; 恶心/呕吐? 止吐剂的使用
药物 烷化剂/Alkylating agents ➢ 非周期特异/Not cell-cycle specific; ➢ 代表药物 • 环磷酰胺/Cyclophosphamide (CTX) • 苯丁酸氮芥（留可然）/Chlorambucil (Leukeran) • 亚硝基脲/nitrosoureas (BNCU, CCNU) ➢ 耐药性/Resistance • Increased ability to repair DNA defects • Decreased cellular permeability to the drug • Increased glutathione synthesis：被GST失活 ➢ 主要毒性/Toxicity (main) 性腺；消化道/GI；骨髓抑制； 常见方案？ 毒性依赖于微粒体酶系活性 不可使用GSH保肝 ANC1500?/PLT100? …… 恶心/呕吐？ 止吐剂的使用 10