gnrh a在婦科腫瘤中的應(yīng)用

GnRH-a在婦科腫瘤中的應(yīng)用上海市第一婦嬰保健院翁雷Newcasesanddeathsforfemale

inU.S.2013NewcasesBreast29%Lung&bronchus14%Colon&rectum9%Uterinecorpus6%Thyroid6%Non-Hodgkinglymphoma4%Melanomaoftheskin4%Kidney&renalpelvis3%Ovary3%Pancrease3%DeathsLung&bronchus26%Breast14%Colon&rectum9%Pancrease7%Ovary5%CACancerJClin2014ClinicalPracticeGuidelinesforGynoncologyFIGOstagingclassificationandclinicalpracticeguidelinesforgynecologiccancersNCCN（NationalComprehensiveCancerNetwork）clinicalpracticeguidelinesinoncology

NCCN2015principlesofprimarysurgery

confinedtoanovaryortopelvis:peritonealcytologicexaminationsallperitonealsurfacesvisualizedanyperitonealoradhesionsuspiciousexcisedorbiopsiedrandomperitonealbiopsyfromthepelvis,paracolicgutters,andundersurfacesofthediaphragm(Papanicolaoustain)intheabsenceofanysuspiciousareas.TAH+BSOwithanencapsulatedmassintactduringremoval.USOforpatientsdesiringtopreservefertility

OmentectomyAorticlymphnodedissectiontoatleasttheleveloftheinferiormesentericarteryandpreferabletotheleveloftherenalvesselsPelviclymphnodesdissectionNCCN2015principlesofprimarysurgery

involvingtheupperabdomen:maximalcytoreduction(residualdisease<1cmoptimalcytoreduction)maximalefforttoremoveallgrossdisease.peritonealcytologicexaminationsTAH+BSOallinvolvedomentumremovedsuspiciousand/orenlargednodesresectedPLD+PALDforpatientswithtumornodulesoutsidethepelvis≤2cm(presumedstageIIIB)

NCCN2015principlesofprimarysurgery

Proceduresforoptimalsurgicalcytoreduction(inallstages)mayinclude:RadicalpelvicdissectionDiaphragmorotherperitonealsurfacestrippingSplenectomyPartialhepatectomyCholecystectomyPartialgastrectomyPartialcystectomyUreteroneocystostomyDistalpancreatectomyNCCN2015Chemotherapyforepithelialovariancancer/fallopiantubecancer/primaryperitonealcancerPaclitaxel135mg/m2IVover24hd1,cisplatin75-100mg/m2IPd2,paclitaxel60mg/m2IPd8Paclitaxel175mg/m2IVover3hd1,carboplatinAUC5-7.5over1hd1Docetaxel60-75mg/m2IVover1hd1,carboplatinAUC5-6IVover1hd1Paclitaxel80mg/m2IVover1h,d1d8d15,carboplatinAUC6over1hd1GOG218CP:carboplatin(AUC5or6)andpaclitaxel(175mg/m2),every3weeksfor6cyclesCP-BV:aboveregimenplusbevacizumab(7.5mg/km),givenconcurrentlyevery3weeksfor5or6cyclesCP-BVBVaboveregimencontinuedfor12additionalcyclesoruntilprogressionofdiseaseICON7phaseIIITreatmentpatientsCP-BV764CP-BVBV764PSFOS17.4NR19.8NRPerrenTJ,ICON7investigators.AphaseIIItrialofbevacizumabinovariancancer.NEnglJMed.2011;365(26):2484-2496

APhaseIIStudyofIntraperitonealPaclitaxelPlusCisplatinandIntravenousPaclitaxelPlusBevacizumabAsAdjuvantTreatment

ofOptimalstageII/IIIEpithelialOvarianCancer

paclitaxel135mg/m2IVover3hoursday1,cisplatin75mg/m2IPday2,andpaclitaxel60mg/m2IPday8.Bevacizumab15mg/kgIVafterpaclitaxelonday1beginningincycle2.Aftersixcyclesofchemotherapy,bevacizumabwasgivenevery3weeksfor17additionaltreatmentResults:41treatedpatients,30(73%)receivedsixcyclesofIV/IPchemotherapyand35(85%)receivedatleastfourcycles.Three(7%)ofthosewhodiscontinuedchemotherapydidsobecauseofcomplicationsrelatedtobevacizumabMedianPFS28.6monthsTheobservedmedianPFSissimilartothatseenwithIP/IVchemotherapyalone

JClinOncol2011Nov7NCCN2015StagingforLesscommonovarianhistopathologies

Malignantgermcelltumors,MalignantSexcord-stromaltumors,Ovarianlowmalignantpotentialtumors,

a(MMMT)

Fertility-sparingsurgeryandcomprehensivestagingcompletesurgicalstagingNCCN2015chemotherapyofmalignantgermcellandsexcordstromaltumorsIB–IIIdysgerminomacarboplatin400mg/m2d1etoposide120mg/m2d1-d3every4wx3BEPbleomycin30uweeklyx9etoposide100mg/m2d1-d5cisplatin20mg/m2d1-d5every3w3-4courses化療時(shí)卵巢功能的保護(hù)Amenorrheafollowingadjuvantchemotherapy

forEBC:4-90%AnnOncol1:183-188JClinOncol16:2651-2658NCIMongr1:105-109RecentResultsCancerRes127:247-255JClinOncol14:1718-1729ChemotherapyInducedAmenorrhea(CIA)osteoporosis,cardiovascular,urogenitalatrophyhotflushes,sleepdisturbance,changeofmoodEffectofchemotherapyonovaries

highrisk:alkylatingagentsintermediaterisk:anthracyclineslowrisk:antimetabolites

BreastCancerResTreat(2008)110:411-416

ChemotherapydrugsAlkylating:CyclophosphamideIfosfamideMelphalanCisplatinCarboplatinOxaliplatinAltretamineAnthracyclines:DactinamycinBleomycinDoxorubicinLiposomaldoxobubicinMitomycinCChemotherapyofGynecologicCancers(secondedition)LippincottWilliams&Wilkins:18-19ChemotherapyDrugsAntimetabolites:MethotrexateFluorouracilGemcitabine

Derivedfromplants:VinblastineVincristineVinoreblineEtopsidePaclitxelDocetaxelTopotecanIrinotecanChemotherapyofGynecologicCancers(secondedition)LippincottWilliams&Wilkins:18-19FertilityOvarianProtectionGnRHagonistscryopreservationofovariantissuefertilizedornon-fertilizedeggsembryosafterIVF持續(xù)使用GnRH激動(dòng)劑，可抑制垂體分泌促卵泡激素（FSH）和促黃體生成素（LH），從而抑制卵巢雌激素的分泌1停藥后，這一作用完全可逆，可迅速恢復(fù)排卵和月經(jīng)周期。1GnRH激動(dòng)劑作用機(jī)制1雌激素雌激素雌激素垂體下丘腦下丘腦下丘腦下丘腦正常急性慢性子宮卵巢醋酸亮丙瑞林制劑脫敏垂體（前葉后葉）正常極度活躍量增加極度活躍量減少GnRH激動(dòng)劑作用機(jī)制GnRH激動(dòng)劑GnRHGnRHGnRHFSH/LHFSH/LHFSH/LHSummaryofnonrandomizedtrialsoffertilitypreservationusingGnRH-ainwomenwithearlybreastcancer

authorGnRH-astudytypeNsummaryofresults

RecchiaGoserelinretrospective,64mensesresumedby86%ofpatients,1pregnancyandbirthofnormalchildRecchiaGoserelinretrospective,100mensesresumedby100%ofpatients<40yandby56%>40y,3pregnancies,2normaldeliveries,1voluntaryabortionFoxLeuprolideretrospective,24mensesresumedby96%ofpatients,6pregnancies,3abortions,1terminatedforDown’ssyndrome,1resultinginalivebirth,1ongoingattimeofreportDelMastroGorserelinphaseII,29mensesresumedby72%ofpatients(94%,<40y42%,>40y)

Cruz.Fertilityandtherapyinbreastcancer.FertilSteril2010

GnRH-a治療子宮內(nèi)膜間質(zhì)肉瘤EffectofsexsteroidonESSprogesteronecausesstromalcellmaturationestrogenmayactasgrowthfactorinthesetumorsGnRH-adecreasesestrogenlevelsalongwithprogesteronetoreducetumorsizeGynecolOncol36:60-65,1990

GynecolOncol36:60-65,1990

DennisScribner,Jr.,

CaseReport46y,12?15cmabdominalmass,LG-ESS(FNA),inoperableLupron7.5mgqmandMegace160mgqd9weekslater,significantreductioninthetumor,allowingforsurgicalresection

GynecolOncol71,458-460,1998GnRH-a治療卵巢顆粒細(xì)胞瘤LeuprolideAcetateforTreatingRefractoryorPersistentGCT6patients,recurrentorpersistentLupron7.5mgq.m.2partialresponses3,11months,PFS4,12months3stablediseasePFS3+,3+,13+months1treatedwithLupronfor24months,NED

JClinEndocrinolMetab1991;72:1036-1041LeuprolideAcetateforTreat