赫赛汀说明书

12420060731200610272007090520081231200903032009040320091104201101242011102720120801201208102[]®HerceptinTrastuzumabInjectionZhusheyongQutuozhuDankang[]DNA(CHO)1.1%20mlL-L-α,α-20[]440mg21mg/ml[]HER21HER235-HER2HER2HER2IHC3+IHC2+/FISH+[]440mg(20ml)/[]‘’HER24mg/kg902mg/kg308mg/kg36mg/kg9017528mg/kg6mg/kg90304152LVEFLVEF441LVEFLVEF≥16LVEFLVEF≥1048LVEFLVEF≤15LVEF8352mg/kg6mg/kg2mg/kg:6mg/kg4mg/kg8mg/kg902mg/kg6mg/kg21mg/ml,pH6.0284mg/kg12mg/kg=Kg×4mg/Kg2mg/Kg21mg/ml8mg/kg36mg/kg=Kg×8mg/Kg6mg/Kg21mg/ml250ml0.9%5%282465%/[][][][][]10%5≥1/10≥1/1001/10≥1/1,0001/100≥1/10,0001/1,0001/10,000/71*/+()+11+18*++9**2%ADRsSOC+1(LVEF)HERA(BO16348)12.612.4112.6NSAPBB31NCCTGN9831AC-TH2324NSAPBB31NCCTGN98316%AC(ACLVEF50%≥15%)NSAPBB31NCCTGN9831+HERA(BO16348)2122NSAPBB31NCCTGN9831HERA(BO16348)LVEFNSAPBB31NCCTGN9831HERA(BO16348)AC-TH(n=1606)AC-T(n=1488)(n=1678)(n=1708)LVEF50%22.8%(366)9.1%(136)8.6%(144)2.7%(46)50%≥10%18.3%(294)5.4%(81)7.0%(118)2.0%(35)50%≥16%11.7%(188)2.2%(33)3.8%(64)1.2%(20)LVEF≥10%20%33.4%(536)18.3%(272)22.4%(376)11.9%(204)LVEF≥20%9.2%(148)2.4%(36)3.5%(59)1.2%(21)101NSAPBB31NCCTGN9831LVEF≥10%50%+-------ACTACT+HT:H2HERA(BO16348)LVEF≥10%50%-------1011(NYHAI−IVIV)(5)ToGA/FP/HFPLVEF6448-906550~861LVEFToGALVEF3LVEFLVEF:/(N=290)()//(N=294)()*LVEF≥10%50%1.1%4.6%50%1.1%5.9%*LVEF≥10%≥50%11.8%16.5%*LVEFLVEFFPn=187HFPn=2374/(N=290)()//(N=294)()6%6%≥3NCICTCAE3.0*3%**1%*99**454012121351.49WHO31%WHO430vs21[HERA(BO16348)]NCI-CTC2~512.5vs6.6[NSAPBB31]0.1vs0[NCCTGN9831]H0649gNCI-CTC31%NCI-CTC452vs0.7[NCCTGN9831]257.1vs4.5[NSAPBB31]NCI-CTC3/432vs2223vs17SOC≥3≥15/(N=290)()//(N=294)()30%27%10%12%133%5%3%5%///≥3NCICTCAE3.0SOC384012%WHOIIIIV60%WHOIIIIV7vs15WHOIIIIV418ToGANCICTCAE3.0≥3FPHFP32NCICTCAE3.0≥3SOCFPHFP1146vs30[H0648g]NCI-CTC2-522vs14[NSAPBB31]3-5/3.3vs1.4[NCCTGN9831]23vs1714NCI-CTC2514vs5[NSAPBB31]NCI-CTC3523.4vs1[NCCTGN9831]NCI-CTC2512vs4[NSAPBB31]NCI-CTC252.5vs0.1[NCCTGN9831]/0.70.3311/3.0vs1.3[NSAPBB31]2.1vs0[H0648g]NCI-CTC256.2vs4.8[NSAPBB31]NCI-CTC351.6vs0[NCCTGN9831]NCI-CTC147vs1[HERA(BO16348)]25ToGA10937%80(28%)NCI-CTCAE3.0FPFP+H4%9%≥3159031ELISAHAHAHAHA616717[][](LVEF)46LVEF≥16%LVEF≥10%/18MUGALVEF•LVEF•3LVEF•6LVEF•4LVEF[]NSAPBB3116%136/844LVEFHERA(BO16348)2.6%44/1678HERA••••••32CHFNSAPBB31NCCTGN98311LVEF≥50%819NSAPBB31NCCTGN9831*2%(32/1677)0.4%(7/1600)HERA2%(30/1678)0.3%(5/1708)*19*I-IVIII-IVH0648g(AC)28%7%19%3%H0648g11%1%4%1%H0649g**7%N/A5%N/A*LVEF**1//20440mg31NCICTC34[]HER2HER2HER2HER2HER221HercepTestTMCONFIRM™anti-HER-2/neu(4B5)PrimaryAntibodyHER-2/NEUIHCHER2FISHpharmDxTMINFORMHER2DNAProbeHER2DNARabbitanti-DNPAntibodyDNPINFORMChromosome17Probe17DDISHHER2ProbeDDISHHER2(FISH)IHCFISHFISHHER2H0648gIHCFISH13NCCTGN9831HERAIHCFISH10HER2HER2HER2ToGAHER2FISHIHC16HER2010%1+10%/222+10%3+10%23[]61242mg/kg25HER2HER22050120150IgG12.52mg/kg3[]18[]37765244133[H0648gH0649g][NSAPBB31NCCTGN9831]32565[]1.5BO15935M77004HER2-+JP16003HER2-JP19959ToGA++[]8mg/kg[]23752[NSAPBB31NCCTGN9831]HER23386HERA(BO16348)NSAPBB31NCCTGN9831HER2IHC3FISHHER226NCCTGN9831NSAPBB31100mmHg200mmHg11ACAC+242160mg/m2600mg/m2NSAPBB3180mg/m23175mg/m212NCCTGN98314mg/kg2mg/kg52/ER/PRDFS3752NSAPBB31NCCTGN983149228066584744/9038T191276653ER/PR53HERA(BO16348)HER2IHC3+FISH≥T1cLVEF55%ECG(180mmHg100mmHg)41:1(n=1693)1(n=1693)ER/PgR8mg/kg36mg/kg52NSAPBB31NCCTGN983127338649218083%13%94%50%ER/PgR57%32%11%96%(1055/1098)109849%543ERPgR47%(512)ER/PgR2cm233594%NSAPBB31NCCTGN9831DFS3NSAPBB31NCCTGN9831HERA(BO16348)DFS10NSAPBB31NCCTGN9831//HERA(BO16348)//6510NSAPBB31NCCTGN9831HERANSAPBB31NCCTGN9831HERA(BO16348)AC→+(n=1872)AC→(n=1880)→(n=1693)→(n=1693)DFS133261127219(95%CI)0.048a0.39,0.590.54(0.44,0.67)p0.0001b0.0001c6292314095%CI0.670.75pNSdNSdCIaCOXbcdNS283ITTNSAPBB31NCCTGN9831NCCTGN9831HERA(BO16348)HER2DFS11NCCTGN9831IHC3+/FISH+81%HERA(BO16348)IHC3+/FISHFISH+/IHCDFS11NCCTGN9831HERA(BO16348)HER2/NCCTGN9831HERA(BO16348)DFS(95%CI)/DFS(95%CI)HER2*IHC3+FISH(+)11700.42(0.27,0.64)910.56(0.13,2.50)FISH(−)510.71(0.04,11.79)8----FISH510.6922580.5329(0.09,5.14)(0.41,0.69)IHC3+/FISH(+)1741.01(0.18,5.65)299^0.53(0.20,1.42)IHC/FISH(+)--------7240.59(0.38,0.93)*HercepTestIHCPathVysionFISH^HERA(BO16348)IHC2+HERA(BO16348)1225416812246266792%50%40%10%41%91%26%HERA(BO16348)DFS1281.4%92.9%1(HR0.29,95%CI0.08-1.08,p=0.0489)HERA(BO16348)123012HERA(BO16348)HERA(BO16348)→(n=68)→(n=54)DFS38(95%CI)0.29(0.08,1.08)p0.0489aOS1395%CI0.30pNSbabNS=(H0648gn=469)H0649gn=2222HER223HER203H0648gH0648g469IHCCTA01+2+3+,3+2+3+334mg/kg2mg/kg175mg/m232116AC60mg/m275mg/m2600mg/m221166531ORR13AC13H0648g:AC+(n=235)(n=234)+(n=92)(n=96)+ACa(n=143)AC(n=138)TTPb,c7.24.56.72.57.65.795%6.9,8.24.3,4.95.2,9.92.0,4.37.2,9.14.6,7.1Pd0.00010.00010.002b45293815503895%39,5123,3528,488,2242,5830,46Pe0.0010.0010.10()b,c8.35.88.34.38.46.425%,75%5.5,14.83.9,8.55.1,11.03.7,7.45.8,14.84.5,8.5()c25.120.322.118.426.821.495%22.2,16.8,16.9,28.612.7,24.423.3,32.918.3,26.6Pd0.050.170.16aAC=()bcKaplan-Meierdeχ2H0648gHER23143214H0648gHER2HER2(N)**(95%CI)**(95%CI)CTA2+or3+4690.49(0.40,0.61)0.80(0.64,1.00)FI