对肺癌法疗课件.ppt

1、Comprehensive Review of Navelbine.Navelbine Oral navelbine vs.IV Navelbine Efficacy Quality of life Convenience Adjuvant chemotherapy with Navelbine Lace meta-analysis Navelbine in first line Histology Navelbine in maintenance therapy Navelbine in elderly Monotherapy.versusversusEquivalent AUCs:I.V.

2、ORAL30 mg/m80 mg/m25 mg/m60 mg/mMarty,Ann.Oncol.20011101001000100000122436Time(h)Blood Conc(ng/ml)1101001000100000122436Time(h)Blood Conc(ng/ml).NAVELBINE I.V.versus ORAL.NAVELBINE I.V.versus ORALSingle agent.Gridelli et al JNCI 1999,p=0.046.24.7024681012CHEMOTHERAPY REGIMENMEDIAN SURVIVAL IN MONTHS

3、:VinorelbineSupportive Care.Kelly J Clin Oncol 2001;Survival:1 YR 36%/38%,2 YR 15%/16%;Resp Rate:28%/25%88024681012CHEMOTHERAPY REGIMENMEDIAN SURVIVAL IN MONTHS:Vinorelbine+DDPPaclitaxel+Carbo.Kelly J Clin Oncol 2001.(N=410).Baseline Compared with Week 25(Using FACT-L)0102030405060708090100Vinorelbi

4、ne+CisplatinPaclitaxel+CarboplatinPERCENT OF PATIENTS:QL:ImpovedQL:Stable.Evaluation of the impact on nursing and pharmacy staff resource and patient waiting time of a switch from IV to oral chemotherapy:a time and motion auditDr Henry TaylorKent Oncology Centre9Cancer Services Collaborative,31st Oc

5、tober 2005.Capacity PlanningFor each patient given IV chemotherapy:4 patients could have been given oral chemotherapy by nursing staff 3 patients could have had their oral chemotherapy prepared by pharmacyUnit:minute.Adjuvant Chemotherapy in NSCLC:A new standard of care?.4%.ASCO 2005 ANITA:OS months

6、Survival Distribution Function1.000.750.500.250020406080100120ObsNVB+CDDP.Good performance status patients with“R0”Anatomic Resection.PopulationPatients with completely resected NSCLCInclusion criteriaCDDP-based vs ObsCDDP-based+PORT*vs PORTNVB+CDDP vs ObsNVB+CDDP+PORT vs PORTIncluded studies5 studi

7、es includedALPI,BLT,IALT,JBR10,ANITA4 studies includedBLT,IALT,JBR10,ANITAPts characteristicsn=4,584IA:8%,IB:30%,II:35%,III:27%n=1,888IA:2%,IB:34%,II:38%,III:26%Main objectiveOverall Survival of CDDP-based regimensOverall Survival of NVB+CDDP regimens*LACE=Lung Adjuvant Cisplatin Evaluation*PORT=pos

8、t-operative RTPignon,JCO 2008,Douillard,JTO 2010Activity of a CDDP-based doublet in an adjuvant treatmentSpecific input of NAVELBINE in a CDDP-based adjuvant treatment.NAVELBINE+cisplatin is the new standard of care as adjuvant treatment for NSCLC6Survival(%)+5.3%withCDDP-based+8.9%with NVB+CDDPLACE

9、 NavelbinePignon,JCO 2008,Douillard,JTO 2010.Navelbine as first line in NSCLC.NVB I.V./ORAL.(n=61)(n=75)(n=77)(n=83)(n=52)(n=150)(n=158)(n=156)MS(m)NVB IV/Oral(n=44)(n=56)Parente Santomaggio Bretti Cremonesi Maguire Tan Helbekkmo Jensen*OBrien*Reck*1997 1998 2001 2003 2003 2005 2007 2007 2004 2006*P

10、hase II trialsMS:8m 12.3mPhase III trial.Histology Matter of Navelbine.Patients characteristicsNVB I.V.30 mg/m D1*NVB Oral80 mg/m D8*CDDP80 mg/m D1(*1st cycle at 25 mg/m and 60 mg/m respectively)3-week cycles x6DCT75 mg/m D1CDDP75 mg/m D13-week cycles x6nMedian ageKPS 80-100Stage IVAdenoK/Squamous19

11、459.4y.99.5%71%41.6%/34.1%19662.1y.100%76%39.3%/33.5%Drug deliveryMedian n of cyclesDose increased at cycle 24.2 cy4.4 cyNot applicableTan,Ann Oncol 2009.23NAVELBINE+CDDP versus docetaxel+CDDP:Similar OS P-value MS(m)9.929.82 0.66895%CI8.61 11.6 8.80 11.5HAZARD RATIO 0.948 0.744 1.209 Tan,Ann Oncol

12、2009.GLOB 3:Adenocarcinoma outcome is improved by chemotherapies.Tan,Ann Oncol 2009GLOB 3 NVB Oral+CDDP armn=190ADK subtype41.6%ptsOther types58.4%ptsORMS29.1%11.7 m26.1%9.0m.Safety profile of Oral vinorelbine was qualitatively comparable to IV regimen.Oral vinorelbine(Navelbine)offers the convenien

13、ce of an oral administration without interfering with the efficacy and the safety of the well-established IV vinorelbine Histology matter in Navelbine?.Navelbine in Maintenance Therapy.271st line metastatic NSCLC-NAVELBINE Oral+CBDCA(1/2-Reck)Phase II trialNVB Oral 80*mg/m/week+CBDCA AUC5 D1 q3w Mai

14、ntenance NVBo 80*cy 5-6(pts with OR or SD)ITT populationMedian ageMedian nb of cycles in combinationNumber of pts receiving maintenancen=5661 37-714 1-452.6%Dose escalation67.3%ORDCPFSMS1-YS17.9%73.2%4.3m9.7m37.1%*after testing myelosensitivity at 60 mg/m/week at the first 3 administrationsHigh effi

15、cacy of NAVELBINE Oral reproducing NVB I.V.dataReck,Lung Cancer 2009.28NAVELBINE Oral+CBDCA(2/2-Reck)Gr.3-4 toxicities(%of pts)NVB Oral+CBDCAMaintenance NVBoNeutropeniaFebrile neutropeniaThrombocytopeniaAnaemiaNausea/VomitingDiarrhoeaFatigue68%7.1%16%22%7%(Gr.3)/7%(Gr.3)4%(Gr.3)2(Gr.3)20%NR3.3%(Gr.3

16、)6.6%0/03.3%(Gr.3)3.3%(Gr.3)The combination of NVB Oral+CBDCA“offers an active and safe regimen for patients with unresectable localized or metastatic NSCLC,for whom palliation coupled with optimal safety is the main end point.”Reck,Lung Cancer 2009.Treatment of Special Populations:Elderly and PS2 p

17、atients.TrialGroupCommentV vs BSCELVISCompletedGV vs VSICOGCompletedG vs V vs GVITA-MILESCompleted.Chemotherapy in Elderly Patients with Advanced NSCLC13%4.576 15%Vinorelbine30%*776 22%Gemcitabine+VinorelbineFrasci14%4.976 -BSC32%*6.5 78 20%VinorelbineGridelli*1 YRMS(mo)N ResponseRegimenAuthor*Gride

18、lli,J Natl Cancer Inst 1999;85:365-376.Frasci et al,Proc ASCO 2001,19:A1895*p0.05.The MILES Phase III Trial:Gemcitabine+Vinorelbine vs Vinorelbine and vs Gemcitabine in Elderly Advanced NSCLC Patients NSCLC 70+years oldChemotherapy nave Stage IIIB(N3 or pleural effusion)or IVPS 0-2RANDOMIZEGridellii

19、 et al.ASCO 2001 Abstract 1230Vinorelbine 30 mg/m2 d1,8Q 3 weeksGemcitabine 1000 mg/m2 d1,8Vinorelbine 25 mg/m2 d1,8 Q 3 weeksGemcitabine 1200 mg/m2 d1,8Q 3 weeks.Single Agent Chemotherapy in Elderly Patients with Advanced NSCLC*Gridelli,J Natl Cancer Inst 1999;85:365-376.Frasci et al,JCO 2000;18(13

20、):2529-2536 Gridelli,J Natl Cancer Inst 2003;95:No5*p0.05Author Regimen N Response MS(mo)1 YR Vinorelbine 78 20%6.5 32%*BSC 76 -4.9 14%Gemcitabine+Vinorelbine 76 22%7 30%*Vinorelbine 76 15%4.5 13%Vinorelbine 233 18.4%8.8 41%Gemcitabine 233 17.3%6.6 26%Gemcitabine+Vinorelbine 237 20%7.6 31%Gridelli*FrasciGridelli.