1、癌症治療的新趨勢個人化的癌症治療,謝瑞坤醫師癌症中心 馬偕紀念醫院癌症安寧緩和醫學會台灣癌症全人關懷基金會,Cancer: Disease of the Genes,癌症的演化是一個多步驟的過程,它包含了許多累積的對細胞遺傳物質的變化而中導致對遺傳物質的損傷所致.,From Clin Cancer Res, 2002; 8:314,癌症不是一日形成的,癌症的治療與預防,癌症也是一種疾病預防重於治療早期診斷早期治療,吸菸人口 Adults 18 Years and Older,Age-adjusted percent,2010 Target,Black male,White male,White
2、 female,Black female,Notes: Data are age adjusted to the 2000 standard population. Survey redesigned in 1997 and data for 1998 and subsequent years may not be directly comparable to earlier years. Source: National Health Interview Survey (NHIS), NCHS, CDC.,肺癌的死亡率,Age-adjusted death rate per 100,000
3、standard population,黑人男性,全部人口,白人男性,White female,Black female,Notes: Data are age adjusted to the 2000 standard population. Source: National Vital Statistics System-Mortality (NVSS-M), NCHS, CDC.,2010 Target,全部男性,Total female,英國成人抽菸比例逐年減少,肺癌死亡率有明顯減少,自1990年以來美國癌症死亡率首次出現減低,美國國家癌病署(NCI)在1996年底宣布在1991-19
4、95年間全美癌症死亡率減少了百分之三.1930年代開始有癌症登記以來首次出現癌病死亡率未增反減的現象.在抗癌戰爭上經由不斷的研究發展,人類也能有嚇阻癌病繼續擴大的能力.,美國癌症死亡率的增減1971-1995,1971-19751976-19801981-19851986-19901991-1995,+0.33% +2.09% +2.41% +1.14% - 2.59%,美國癌症死亡率的減低(91-95),所有部位肺癌乳癌攝護腺癌大腸直腸癌卵巢癌子宮頸癌,-2.6% -1.5% -6.3% -6.2% -5.4% -4.8% -9.7%,現代醫學控制癌症的方法,現代醫學控制癌症的方法,實證醫學
5、 (EBM, Evidence-based Medicine),以流行病學和統計學的方法，從龐大的醫學資料中嚴格評讀、綜合分析並找出值得信賴的部分，並將所能獲得的最佳文獻證據，應用於臨床工作中，使病人獲得最佳的照顧。,傳統醫療 vs 實證醫學,傳統醫療: Identify the Problem Use your Experience Ask a Colleague Consult a Textbook Read a Review,實證醫學 Formulate a QuestionConduct Search of LiteratureSelect Key ArticlesCritically
6、 Judge the ArticlesApply result to Patient,癌症臨床試驗的重要性,目前我們在治療癌症的各種進步都是經由臨床試驗而來的癌症患者可以活的更久都是因為臨床試驗帶來的治療演進的結果,Cancer: Disease of the Genes,癌症的演化是一個多步驟的過程,它包含了許多累積的對細胞遺傳物質的變化而中導致對遺傳物質的損傷所致.,癌症與基因,The changes that cause a cancer in an individual patient is called the molecular signature or genetic finge
7、rprintThe signature dictates how aggressive it will be and what treatment will work bestWe can now measure the genes in a tumor and classify the patient on the basis of its gene signature into groups,個人化醫療 Personalized Medicine,Personalized Medicine what is it?Then and now what we can do today that
8、we couldnt do before Biomarkers and (genetic) testingDose and drug selection some key points to considerDrugtest co-development a paradigm change?Theme:Evidence and Benefit- Risk considerations,個人化醫療 Personalized Medicine,The management of a patients disease or disposition by using molecular knowled
9、ge to achieve the best possible medicinal outcome for that individual,個人化醫療 Personalized Medicine,Personalized medicine is the use of information from a patients genotype to: Initiate a preventative measure against the development of a disease or condition , or Select the most appropriate therapy fo
10、r a disease or condition that is particularly suited to that patient.,乳癌死亡率降低,外科病理的演進, Era of Autopsy Pathology Curious physicians (1700 early 1900s) Era of Surgical Pathology Branched out from Surgery (early to mid-1900s) Era of Personalized Medicine Integrated Anatomic and Clinical Pathology (turn
11、 of the century),Tumors genetic signature stratifies patients risk for metastasis (OncodxTM, MamoprintTM etc),Breast Cancer is Not ONE Disease,IHC-based subtypes,Luminal A: ER+ and/or PR+, HER2-Luminal B: ER+ and/or PR+, HER2+Basal-like: ER-, PR-, HER2-, CK 5/6+ and/or EGFR+HER2+/ER-Unclassified: ne
12、gative for all five markers,JAMA 295:2492, 2006,人種的不同也有乳癌次分類的不同,Symptoms vs. Genetic-based Medicine,Symptoms-based Symptomatic diagnosis, prescription & monitoring Treatment Targets selected based on largest population Blockbuster drug for all patients effective in only 40-60% and can have adverse d
13、rug reactions (ADR) Reactive,Symptoms vs. Genetic-based Medicine,Genetic-based Molecular Diagnosis Risk-stratification by molecular Drug-targeted therapy Less or no ADR Molecular monitoring of disease Preventive,Genetics and Genomics in Clinical Medicine,Assessment of risk (eg., Breast cancer and Co
14、lon cancer)Pharmacogenomics Efficacy of drugs based on genomic changesPharmacogenetics Efficacy of drugs based on genetic differences,Personalized Medicine involve,Risk stratificationInform treatment selectionInform dosagePrognostic testingTreatment monitoringImprove or optimize clinical treatment p
15、athways-,Genomic Tools for Prediction andPersonalized Care,Pharmacogenomics Strategy,大腸直腸癌藥物治療的預後與相關代謝的基因表現相關,個人化癌症藥物治療,Which drug should I use?Tamoxifen(ER), Herceptin(Her-2),Glivec(CML Bcr-Abl),Erbitux(EGFR),Tarceva(EGFR)How much of the drug do I need?Camptosar(UGT1A1)Is the drug working ?Glivec(C
16、ML QT-PCR for Bcr-Abl),Personalized Medicine: Fears,PharmaPayersDoctorsPatientsRegulatorsDiagnostics,Reduce marketAdd cost without returnToo prescriptiveWill I be denied access to new drugs?How do handle new complexities?More tests with poor reimbursement,Personalized Medicine,The right drug or treatment, atthe right time, for the rightpatient, at the right cost對的治療 對的時間 對的患者 對的代價,
