食管癌同步放化疗【治疗】课件.ppt
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1、陕西肿瘤放疗年会2008年12月,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,食管癌同步放化疗西安交通大学医学院第二附属医院肿瘤中心放疗专业马红兵 王西京 任宏涛 王宝峰,1,肠道相关,概述药物临床进展,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,2,肠道相关,Cancer statistics, 2008. CA Cance
2、r J Clin. 2008 Mar-Apr;58(2):71-96. Epub 2008 Feb 20,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,3,肠道相关,2004年全国40个观察点统计分析,食管癌发病率居第四位。全世界每年新发食管癌病例约万;我国的食管癌发病率居世界之首,发病人数占世界发病总数的60%, 13/10万/年,男性的发病率是女性的二倍。 。接受手术的5年生存率为15%39%而接受放疗者为8%15%,西安交通大学医学院第二附属医院,SECO
3、ND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,概述,我国食管癌,4,肠道相关,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,Surgical OncologyRadiation OncologyMedical OncologyBiological and Target TherapyThe traditional Chinese medicine,治疗手段,概述,5,肠
4、道相关,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,目前,食管癌还是一个需多学科部门联合综合治疗以提高临床疗效的恶性肿瘤。,放射治疗 局部病变药物治疗 微小转移,肿瘤治愈,一个美好的设想:,概述,6,肠道相关,近年,综合治疗显示优势 先进的放疗技术新的化疗药物精确放疗、药物、生物靶向治疗 肿瘤综合治疗的希望,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTON
5、G UNIVERSITY,概述,7,肠道相关,离体细胞研究、分子生物学机制的研究有助于阐明综合治疗的生物学机制,对探讨临床最佳综合治疗方案有着重要的意义。,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,机制,概述,8,肠道相关,Spatial cooperationTemporal cooperationSelecting toxicity depending on cell cycle phaseDecrease in tumor mass and reoxy
6、genationSelecting toxicity for hypoxic cellsCytokinetic cooperationDNA damage Cell apoptosis,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,机制,概述,9,肠道相关,药物,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,10,肠道相关,一线药
7、物(90年代以前的 )顺铂、5Fu、阿霉素 二线药物(90年代以后)泰素、泰索蒂、诺维本、健择、 半合成的喜树碱衍生物、新一代铂类生物靶向药物,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,药物,11,肠道相关,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,5Fu,抗代谢药2. 在体内转变为5氟尿嘧啶脱氧核苷 抑制胸腺嘧啶核甙合成
8、酶,影响DNA的生物合成3、能掺入RNA中干扰蛋白质合成4. 对有氧和乏氧细胞有相同的杀伤作用,药物,12,肠道相关,5Fu增敏机制作用于放射抗拒的S期细胞干扰S期调控点实验室证实,放疗期间持续给药可以增敏,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,药物,13,肠道相关,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,甲酰四氢叶
9、酸,顺铂,加强,5Fu,生化调节机制,4 用药时间,放疗后5min8h,5 用药量,200375mg/m2,5Fu特点:,药物,14,肠道相关,特点:吸收后在体内逐渐变为氟尿嘧啶而起作用 其作用机理与氟尿嘧啶相同, 在体内能干扰、阻断DNA、RNA及蛋白质的合成 其毒性只有氟尿嘧啶的1/41/7 化疗指数为氟尿嘧啶的2倍 血液中半衰期为5h 用药量,一般5001000mg/day慢性毒性试验中未见到严重的骨髓抑制,对免疫的影响较为轻微。,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG
10、UNIVERSITY,新一代 替加氟 Tegafur Injection,药物,15,肠道相关,卡莫氟(Carmofure)特点:不需经过肝脏的药物代谢而释放出5-Fu在血液、淋巴液、腹腔积液以及肿瘤组织中保持高浓度。,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,药物,16,肠道相关,卡培他滨(Caoecitabine)希罗达由于最后催化后形成5-Fu的胸苷磷酸化酶在瘤组织中的浓度为正常组织中的4倍,口服后瘤组织中的5-Fu浓度是静脉给予相同剂量的127倍。,
11、西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,药物,17,肠道相关,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,顺铂 Cisplatin,PDD,DDP,1 铂的金属络合物,作用似烷化剂,2 主要作用靶点为DNA,作用于DNA链间及链内交链,形成DDPDNA复合物,干扰DNA复制,或与核蛋白及胞浆蛋白结合。,3 属周期非特异性药
12、,药物,18,肠道相关,用药量顺铂的抗肿瘤作用,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,浓度依赖性,时间依赖性,顺铂小剂量长期用药抑制肿瘤细胞对放疗所致亚致死性损伤修复抑制和潜在致死性损伤的修复,药物,顺铂最低临床应用剂量 6mg/m2/d,19,肠道相关,顺铂与放疗的相互作用阳离子与DNA链碱基作用改变DNA修复辐射增加DNA单链的修复,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLE
13、GE OF XIAN JIAOTONG UNIVERSITY,药物,20,肠道相关,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,5Fu,顺铂,二者对放射增敏有协同作用,增敏效果与给药时间有关,顺铂在放疗前16h,5Fu持续给药,增敏效果最佳,药物,21,肠道相关,卡铂 Carboplatin在乏氧的条件下卡铂的增敏作用高于顺铂奥沙利铂(乐沙定, 草酸铂)L-OHP复合体DDP复合体 靶分子和作用机制不同 抗瘤谱不同萘达铂 肾毒性、胃肠道反应及骨髓抑制均较DDP
14、轻,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,药物,22,肠道相关,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,紫杉类醇药物(taxanes),泰素、紫素、特素、紫脘素,Paclitaxel, Taxol, PTX,机制,使微管不可逆的聚集干扰细胞的有丝分裂,主要作用于G2晚期和M期,具有显著的放射增敏作用,药物,23,肠道
15、相关,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,是微管解聚抑制剂,其作用于微管/微管蛋白系统,通过促进微管双聚体装配成微管,且通过防止去多聚化过程而使微管稳定,阻滞细胞于G2和M期,从而抑制癌细胞的有丝分裂和增殖。,多西紫杉醇,泰索帝、多西他赛、Docetaxel/TXT,机制,特点,稳定微管的作用比紫杉醇强2倍,药物,24,肠道相关,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE
16、OF XIAN JIAOTONG UNIVERSITY,健择,gemcitabine hydrochloride,盐酸吉西他滨,细胞周期特异性抗代谢类药物,作用于DNA合成期(S期)的肿瘤细胞在一定的条件下,可以阻止G1期向S期的进展,药物,25,肠道相关,分子靶向药物EGFRI (EGFR抑制剂)放射激活EGFR 抗拒放射EGFRI增加肿瘤细胞的放射敏感性机制阻止细胞进入S期增加放射诱导的细胞凋亡抑制放射诱导的EGFR磷酸化抑制放射损伤的修复,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOT
17、ONG UNIVERSITY,药物,26,肠道相关,临床进展,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,临床进展,27,肠道相关,N Engl J Med. 1992 Jun 11;326(24):1629-31. (RTOG8501)Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus.
18、,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,METHODS. This phase III prospective, randomized, and stratified trial was undertaken to evaluate the efficacy of four courses of combined fluorouracil (1000 mg per square meter of body-surface area daily for f
19、our days) and cisplatin (75 mg per square meter on the first day) plus 5000 cGy of radiation therapy, as compared with 6400 cGy of radiation therapy alone, in patients with squamous-cell carcinoma or adenocarcinoma of the thoracic esophagus. RESULTS. The median survival was 8.9 months in the radiati
20、on-treated patients, as compared with 12.5 months in the patients treated with chemotherapy and radiation therapy. In the former group, the survival rates at 12 and 24 months were 33 percent and 10 percent, respectively, whereas they were 50 percent and 38 percent in the patients receiving combined
21、therapy (P less than 0.001). Seven patients in the radiotherapy group and 25 in the combined-therapy group were alive at the time of the analysis. Severe and life-threatening side effects occurred in 44 percent and 20 percent, respectively, of the patients who received combined therapy, as compared
22、with 25 percent and 3 percent of those treated with radiation alone.,28,肠道相关,RTOG85-01随机对照试验首次证明同步放化疗生存期明显优于单纯放疗这一篇文章被认为是食管癌非手术治疗中,具有里程碑意义的重要论文。本文的发表使得同期放化疗成为食管癌的标准治疗方案。同步放化疗已被美国NCCN推荐治疗不可切除的食管癌患者。,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,29,肠道相关,1: J
23、AMA. 1999 May 5;281(17):1623-7. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group.,西安交通大学医学院第二附属医院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY,PATIENTS: Patients
24、had squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0( stage), adequate renal and bone marrow reserve, and a Karnofsky score of at least 50. MethodsInterventions Combined modality therapy (n = 134): 50 Gy in 25 fractions over 5 weeks, plus cisplatin 75 mg/m2 intravenously on the first d
25、ay of weeks 1, 5, 8, and 11, and fluorouracil, 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1, 5, 8, and 11. In the randomized study, combined therapy was compared with RT only (n = 62): 64 Gy in 32 fractions over 6.4 weeks.RESULTS:at 5 years of follow-up the overall survival f
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