台湾药师5A工作模式-索拉菲尼在肝细胞癌中的进展

1SorafenibinAdvancedHepatocellularCarcinoma報告地點：萬芳醫院報告時間：2009/11/6報告者：和信醫院李建勳藥師指導藥師：2FiveA’s•Assess：了解臨床的需求（ClinicalProblem）•Ask：發現問題的所在（Question）•Acquire：找尋最好的資料（BestEvidence）•Appraise：分析資料（Validity,Importance）•Apply：應用在病人身上（Patient）3ClinicalSituation•Mr.Chengisa60yearoldmalepatient.HewasdiagnosedashepatitisBandCvirusinfectionrelatedhepatocellularcarcinoma(HCC)on2003.•Hehasreceivedradiotherapyduring2003/1/24~3/6,transarterialchemoembolization(TACE)during2006/3/4~2007/12/4,computertomography-guidedradiofrequencyablation(RFA)on2008/8/5.•In2009April,abdominalsonographyshowedthatHCCprogresstoretroperitoneallymphnodes,whichissuspectedextrahepaticseedingtumorbetweenabdominalwallandrightlobeliver.Atthattime,thelabdatashowedelevatedalpha-fetoprotein(AFP)93.46ng/mL.•Atthattime,thedoctorconsideredsorafenib400mgPOBIDforthispatient.Issorafenibeffectiveforthispatient?4FiveA’s•Assess：了解臨床的需求（ClinicalProblem）•Ask：發現問題的所在（Question）•Acquire：找尋最好的資料（BestEvidence）•Appraise：分析資料（Validity,Importance）•Apply：應用在病人身上（Patient）5臨床問題的種類•背景問題（BackgroundQuestions）：對疾病的基本認識–5W1H：Who,Where,What,When,How,Why–疾病的某一面向•前景問題（ForegroundQuestions）：對病人的特定問題–處理某疾病病人的特定問題–每個病人有不同的特性：年齡、性別、伴隨疾病與疾病嚴重程度等6Epidemiology•肝癌是全球排名第五位的癌症，每年約有五十萬至一百萬的新病例。•肝癌更是死亡率第三位的癌症，全球每年約有六十萬人死於肝癌。•全球肝癌的盛行率有地理分佈的差異，低盛行區如北美和中美洲等，其盛行率約每10萬人口3-4人；而亞太地區屬於肝癌高盛行區，盛行率高達每10萬人口30-40人。•西元2000年全球肝癌患者，亞洲地區高達44萬人，而北美地區只有1萬2仟人，全球肝癌患者約75%集中於亞洲地區。•肝癌為台灣10大癌症發生率的第二位，每10萬人口發生率男性約26人、女性約8人，男女比例約3:1。林志陵,高嘉宏.肝癌的流行病學.中華癌醫會誌.2008;24(5):277-2817RiskFactors•Livercirrhosis•HepatitisBVirus•HepatitisCVirus•Alcohol•Cigarettesmoking•Betelnut•Afaltoxin•Obesity•Fattyliver•Non-alcoholsteatohepatitis(NASH)•Diabetes•Hereditarytyrosinemia•Hepaticporphyria•Genetichemochromatosis•α1antitrypsindeficiency林志陵,高嘉宏.肝癌的流行病學.中華癌醫會誌.2008;24(5):277-2818ClinicalFeatures•CommonSymptoms–Abdominalpain–Weightloss–Weakness–Fullnessandanorexia–AbdominalSwelling–Jaundice–Vomiting•CommonPhysicalSign–Hepatomegaly–Hepaticbruit–Ascites–Splenomegaly–Jaundice–Wasting–FeverDeVitaVT,etal.Devita,Hellman&Rosenberg’sCancer:Principles&PracticeofOncology,8thEdition9Diagnosis•Radiology–X-ray–Sonography–Computedtomography(CT)–Magneticresonanceimaging(MRI)•Biopsy•Alpha-fetoprotein(AFP)SerologyDeVitaVT,etal.Devita,Hellman&Rosenberg’sCancer:Principles&PracticeofOncology,8thEdition10TreatmentOption•Surgery–Partialhepatectomy–Livertransplantation•LocalAblativeTherapy–Cryosurgery–Microwaveablation–Ethanolinjection–Aceticacidinjection–Radiofrequecyablation(RFA)•RegionalTherapy(hepaticarterytranscathetertreatments)–Transarterialchemotherapy–Transarterialembolization(TAE)–Transarterialchemoembolization(TACE)–Transarterialradiotherapy–90Ymicrospheres–131Ilipiodol•Conformalexternal-beamradiationtherapy•SystemicTherapyDeVitaVT,etal.Devita,Hellman&Rosenberg’sCancer:Principles&PracticeofOncology,8thEdition11StagingSysteminHCC1.除了腫瘤侵犯程度外，需考慮肝臟存留機能2.病理報告取得不易，臨床分期應用廣泛3.依應用目的區分預後的預測與治療方法的選擇12StagingSystem•Prognosis–TNM–Okuda–CLIP(CanceroftheLiverItalianProgram)–JIS(JapaneseIntegratedScore)•Treatment–BCLC(BarcelonaClinicLiverCancer)13StagingSystem–TNM盧勝男,顏毅豪,林芷芸等.肝細胞癌之臨床分期.中華癌醫會誌.2008;24(5):295-30314StagingSystem–Okuda15StagingSystem–CLIPCLIP:CanceroftheLiverItalianProgram16StagingSystem–JISJIS:JapaneseIntegratedScore17StagingSystem–BCLCBCLC:BarcelonaClinicLiverCancerBruixJandShermanM.Hepatology2005;42(5):1208-123618TreatmentGuideline–JSHKudoM.Oncology2007;72(supp1):2-15JSH:JapanSocietyofHepatology;TAI:transcatheterarterialinfusionchemotherapy，也稱作hepaticarterialinfusion(HAI)19臨床問題的種類•背景問題（BackgroundQuestions）：對疾病的基本認識–5W1H：Who,Where,What,When,How,Why–疾病的某一面向•前景問題（ForegroundQuestions）：對病人的特定問題–處理某疾病病人的特定問題–每個病人有不同的特性：年齡、性別、伴隨疾病與疾病嚴重程度等20P.I.C.O.One-sentencedQuestion（請用一句話表達你的問題）AstoadvancedHCCpatient,cansorafenibimprovesurvival?PatientorProblem（描述病患、疾病或病徵的型態）HepatocellularcarcinomaInterventionorInvestigation（包括治療、檢驗、或預後因子）SorafenibComparison（通常用於比較目前的治療或診斷）PlaceboOutcome（對病患有意義的臨床結果）SurvivalTypeofQuestion■Therapy□Diagnosis□Prognosis□Harm□Others___________TypeofStudyDesign■Meta-analysis■RCT□CohortStudies□CaseControlStudies□CaseSeries□CaseReports21FiveA’s•Assess：了解臨床的需求（ClinicalProblem）•Ask：發現問題的所在（Question）•Acquire：找尋最好的資料（BestEvidence）•Appraise：分析資料（Validity,Importance）•Apply：應用在病人身上（Patient）2223搜尋策略：□Systems□Summary□Synopses□Synthesis□Studies關鍵字PrimaryorMeSHTerm同義字1同義字2PHepatocellularcarcinomaORORANDISorafenibORORANDCPlaceboORORANDOSurvivalORORAND搜尋結果174articles:limittoclinicaltrials(byreviewer)1.LlovetJM,RicciS,MazzaferroV,etal.NEnglJMed2008;359(4):378-90(PhaseIIITrial)2.ChengAL,KangYK,ChenZ,etal.LancetOncol2009;10(1):25-34(PhaseIIITrial)3.Abou-AlfaGK,SchwartL,RicciS,etal.JClinOncol2006;24:4293-4300(PhaseIITrial)4.StumbergD,ClarkJW,AwadaA,etal.TheOncologist2007;12:426-437(PhaseITrial)5.FuruseJ,IshiiH,NakachiK,etal.CancerSci2008;99:159-165(PhaseITrial)6.WornsMA,WeinmannA,PfingstK,etal.JClinGastroenterol2009;43:489-495(Smallsamplesize,regardlessofliverfunction,andnegativeresults)7.11articlesshowstheefficacyofcombinationwithothersystemicchemotherapy資料來源：□UpToD