肺癌同步放化療進(jìn)展

1、同步放化療在NSCLC的進(jìn)展,,主要內(nèi)容,放療在早期NSCLC的進(jìn)展同步放化療與靶向藥物治療NSCLC的進(jìn)展同步放化療聯(lián)合培美曲塞治療NSCLC的研究進(jìn)展同步放化療在晚期NSCLC的進(jìn)展,放療在早期NSCLC的進(jìn)展同步放化療與靶向藥物治療NSCLC的進(jìn)展同步放化療聯(lián)合培美曲塞治療NSCLC的研究進(jìn)展同步放化療在晚期NSCLC的進(jìn)展,Stereotactic ablative radiotherapy (SABR) in po

2、tentially operable Stage I non-small cell lung cancer patients,立體定向消融放療治療潛在可手術(shù)的I期非小細(xì)胞肺癌患者Frank J. LagerwaardDept. of Radiation Oncology VUmc Cancer Center Amsterdam,I期NSCLC經(jīng)SABR治療后的局部控制情況,,,不選擇手術(shù)的原因,SABR對潛在科手術(shù)病人的基線特征,t

3、hose with prior high-dose (chemo-)radiotherapy or pneumonectomy (N=23)?GOLD Class ≥3 (N=216)?WHO performance score ≥3 (N=23)?因共患心血管疾病排除手術(shù)的(N=94)?并發(fā)其他腫瘤的(N=50)?因主要共患病除外手術(shù)的, e.g. 新發(fā)冠心病, 腎衰(N=68),SABR的治療劑量選擇,Performed

4、at VUmc since April 2003T1 tumors (≤ 3 cm), 腫瘤未達(dá)縱膈和胸壁–3 x 18 Gy @80%; 3 fx/week (BED 134 Gy)T1 tumors 達(dá)胸壁和縱膈, and T2 tumors–5 x 11 Gy @80%; 3 fx/week (BED 116 Gy)Tumors 臨近心包，臂叢神經(jīng)或肺門–8 x 7.5 Gy @80%; 3 fx/week (BED

5、105 Gy),SABR的主要 毒性,SABR治療117例潛在可手術(shù)患者的結(jié)果,結(jié)論,應(yīng)用SABR是可行的治療后30天死亡率為0%，對比該群患者術(shù)后死亡率為2.6%盡管多數(shù)老年病人共患病率很高，經(jīng)SABR治療后中位生存仍超過5年鼓勵(lì)內(nèi)鏡分期[Nakajima T, 2010; Harley D, 2010]SABR數(shù)據(jù)支持隨機(jī)入組,,放療在早期NSCLC的進(jìn)展同步放化療與靶向藥物治療NSCLC的進(jìn)展同步放化療聯(lián)合培美曲塞治療

6、NSCLC的研究進(jìn)展同步放化療在晚期NSCLC的進(jìn)展,LCCC 0511: Phase I/II Trial of Induction Carboplatin/Paclitaxel plus Bevacizumab followed by Concurrent Thoracic Conformal Radiotherapy with Carboplatin/Paclitaxel, Bevacizumab and Erlotinib i

7、n Stage IIIA/B NSCLC,卡鉑紫杉醇聯(lián)合貝伐單抗行誘導(dǎo)治療繼之以同步胸部適型放療聯(lián)合卡鉑紫杉醇，貝伐單抗和厄羅替尼治療IIIA/B期NSCLC的I/II期臨床研究MA Socinski on behalf of the co-authorsUniversity of North Carolina, Yale University, Wake Forest University and Northeast Medica

8、l Center,實(shí)驗(yàn)設(shè)計(jì),入組病人基線特征,Age (yrs), median (range) 61 (34-74)Sex (M:F) 23 (51%):18 (49%)Stage (IIIA:IIIB) 29

9、 (64%):16 (36%)PS 0:1 26 (71%):13 (29%HistologyAdeno 27 (60%) Squamous

10、 12 (27%)Lg Cell 4 (9%)NSCLC NOS 2 (4%)RaceCaucasian （高加索） 34 (78%)Black （黑人）

11、 9 (20%)Asian 2 (4%)FEV1(£), median (range) 2.4 (0.8-3.9),發(fā)生率多于等于1個(gè)病人且大于等于3級的毒性統(tǒng)計(jì),反應(yīng)率–RECIST(n=45),Inductio

12、n RR –39% (95% CI, 24-55%)ORR –60% (95% CI, 44-75%) *Judged 2-6 months after completion of RT,LCCC 生存結(jié)果,首要終點(diǎn)是PFS –假設(shè)檢驗(yàn)= PFS at 1 year = 50%排除值if PFS > 70%,LCCC高劑量同步放化療的相關(guān)臨床實(shí)驗(yàn),Socinski MA et

13、al Cancer 92:1213-23, 2001, Marks L et al J Clin Oncol 22:4329-40, 2004, Socinski MA et al J Clin Oncol 22:4341-50, 2004, Stinchcombe TE et al J Thorac Oncol 3:250-7, 2008, Socinski MA et al J Clin Oncol 26:2457-63, 2008

14、, Socinski MA et al J Clin Oncol 27:389s, 2009,LCCC 0511-結(jié)論,誘導(dǎo)CbP + Bev 是可以耐受并有效的同步Erlotinib + Bev 繼之以強(qiáng)烈的同步放化療治療非鱗癌的NSCLC 的前提是 ….放療參數(shù)要預(yù)期設(shè)定對食管炎行最佳支持治療首要毒性是食管炎(經(jīng)常為遲發(fā)型)聯(lián)合Erlotinib + Bevacizumab 不可行This approach was as

15、sociated with late PH in squamous histology patientsPFS and OS 的結(jié)果相對于我們的歷史經(jīng)驗(yàn)不被看好基于實(shí)驗(yàn)中觀察到得毒性加倍, 應(yīng)用Bev 和chemoRT 不被推薦,MultimodAlity treatment with Radio-chemoTherapy and Erlotinib in advanced NSCLC (MARTE trial)進(jìn)展期NSCLC放

16、化療聯(lián)合厄羅替尼的多模式治療（MARTE實(shí)驗(yàn)）,Sara RamellaRadiation Oncology Campus Bio-Medico University, Rome (Italy),材料和方法,之前經(jīng)過化療目前正在行放化療的病人包括局限野放療(IF RT) 中值升高至59.4 Gy, 標(biāo)準(zhǔn)分割(1.8Gy/day)Erlotinib (E) 150 mg/dayChemotherapy: Gemcitabi

17、ne (GEM) 300 mg/m2/week (E-GEM group)Pemetrexed (PEM) 500mg/m2 every 3 weeks (E-PEM group),病人基線特征和治療相關(guān)毒性,病人基線特征和毒性統(tǒng)計(jì)數(shù)據(jù),有效性,隨訪范圍6-45 months整體人群:中位生存23.3 mPFS 4.7 m,27.9 vs 19.3 months; p=0.021,7.5 vs 3.7 months; p=0.0

18、5,27.9 vs 18.2 months; p=0.004,23.1 vs 22 months; p=0.791,非鱗癌總生存,鱗癌總生存,,,結(jié)論,臨床前期數(shù)據(jù)證實(shí)厄羅替尼的靶向治療有放射增敏作用之前經(jīng)過多次化療的病人行厄羅替尼聯(lián)合同步放化療治療是可行的有效的臨床生物學(xué)標(biāo)志物保障了放射治療的效應(yīng),Determination of standard dose cetuximab together with concurrent i

19、ndividualised, isotoxic accelerated radiotherapy and cisplatin-vinorelbine for patients with stage III non-small cell lung cancer: A phase I study(NCT00522886),測定標(biāo)放療準(zhǔn)計(jì)量的西妥昔單抗聯(lián)合同步個(gè)體化，同毒性加速放療聯(lián)合順鉑長春瑞賓治療III期非小細(xì)胞肺癌的I期臨床研究

20、Anne-Marie C. Dingemans Gerben Bootsma Angela van Baardwijk Bart Reijmen Rinus Wanders Monique Hochstenbag Arne van Belle Ruud Houben Philippe Lambin Dirk de Ruysscher,治療流程表,*Vinorelbine: step 1 10 mg/m2d 1-8,

21、 8 mg/m2 d22-29 step 2 20 mg/m2d 1-8, 8 mg/m2 d22-29 step3 20 mg/m2d 1-8, 15 mg/m2 d 22-29,毒性,治療3個(gè)月后經(jīng)FDG-PET測定代謝反應(yīng) (N=22) ? CR:8 ? PR:11 ? PD:3結(jié)論 ?

22、同步放化療聯(lián)合順鉑，長春瑞賓及西妥昔單抗時(shí)可行的 ?長春瑞賓不能選擇最大劑量 ?毒性在預(yù)期內(nèi) ?3月后治療結(jié)果令人鼓舞,,放療在早期NSCLC的進(jìn)展同步放化療與靶向藥物治療NSCLC的進(jìn)展同步放化療聯(lián)合培美曲塞治療NSCLC的研究進(jìn)展同步放化療在晚期NSCLC的進(jìn)展,力比泰卡鉑同步3D適形放療后以力比泰卡鉑鞏固化療治療中國局部晚期NSCLC患者,Ma S, et al. ASCO 2009 abstract

23、 e18502.,摘要e18502：研究設(shè)計(jì),摘要e18502：研究結(jié)果 – 緩解情況,摘要e18502：研究結(jié)果 – 不良反應(yīng),放療在早期NSCLC的進(jìn)展同步放化療與靶向藥物治療NSCLC的進(jìn)展同步放化療聯(lián)合培美曲塞治療NSCLC的研究進(jìn)展同步放化療在晚期NSCLC的進(jìn)展,15-year (very) long-term survival (VLTS) and competing risks (CR) analysis of i

24、nduction (IND) chemotherapy (CTx) with three cycles cisplatin(P)/etoposide(E) followed by concurrent (cc) chemoradiation (CTx/RTx) PE/45 Gy (1.5 Gy bid) plus surgery (S) = TRIMODALITY –phase-II West German Cancer Centre

25、(WGCC) trial (JCO 98).R.Hepp1, T.C.Gauler2, C. Poettgen1, S. Korfee2, S. Bildat2, G. Stamatis3, S. Seeber4, H. Wilke4, V. Budach5, M. Stuschke1, W. E. E. Eberhardt2,西德癌癥中心TRIMODALITY II期臨床試驗(yàn)：三周期EP誘導(dǎo)化療繼以同步放化療聯(lián)合手術(shù)治療的一項(xiàng)15

26、年長期生存和競爭風(fēng)險(xiǎn)分析,試驗(yàn)設(shè)計(jì),OS (stage), OS (R0) and OS (R0: pCR vs no pCR),Fig. 2. OS (stage),Fig. 3. OS (R0),Fig. 4. OS (R0: pCR),LTS/VLTS 在選擇性亞群的CR分析,Tab.1. VLTS in selected subgroups,Fig.5. Competing Risk-analysis,結(jié)論,LTS/VLTSon

27、theWGCC-trialJCO98定義為第一個(gè)選擇性可切除IIIA期NSCLC患者的隨機(jī)對照多中心臨床試驗(yàn)探索性分析顯示前期治療對15年長期結(jié)果無影響基于選擇性的R0-可切除的IIIA和IIIB期患者繼以誘導(dǎo)治療手長期隨訪結(jié)果優(yōu)60個(gè)月的競爭性風(fēng)險(xiǎn)分析提示(心血管，肺疾病，再發(fā)肺癌和再發(fā)腫瘤是香港風(fēng)險(xiǎn) (5yrs),SOCCAR trial results:,Comparing toxicity and efficacy of

28、hypofractionated concurrent,chemoradiation to published regimens,Cancer Research UK & UCL Cancer Trials Centre,N O’Rourke, J Maguire, R McMenamin, C Peedell, M Snee,????,Funding: CRUKSponsor: Universi

29、ty CollegeLondonTrial administration: UCLcancer trials centreSupported by British,Thoracic Oncology Group,O’Rourke, N: support for meetingRocheMaguire, J: research support andspeakers honoraria:Pierr

30、e Fabre, Astra Zeneca;advisory boards: Eli LillyMcMenamin,R: speakers honoraria:Pfizer; advisory boards: Bayer, GSK;support for meetings: GSK, Ibt,Ferring, Boeringer,Snee, M:,nil,Cancer Research UK & UCL C

31、ancer Trials CentreTrial funding and Disclosure,3,CONCURRENT ARM55Gy/20f/4weekscisplatinum 80mg/m2 weeks 1,4vinorelbine 15mgs/m2 weekly4 weekscisplatinum 80mg/m2 day 1vinorelbine 25mg/m

32、2 d 1, d 82 cycles,SEQUENTIAL ARMcisplatinum 80mg/m2 day 1vinorelbine 25mg/m2 day 1, 84 cycles4 weeks55Gy/20f/4weeks,SOCCAR,Trial Design病理學(xué)確診NSCLC stage III , PS 0-1,CT

33、7; mediastinoscopy, PET-CTunsuitable for surgery,SOCCAR,NSCLC Stage III PS 0 - 1,CON,SEQ,nmedian1 year2 year3 year5 yearLocal PD,6727.4 m73.1%54%38%33.6%10%,5918.6 m83.1%42%27%N

34、R22%,ConSeqMonths,Cancer Research UK & UCL Cancer Trials CentreConcurrent Schedules Compared,Trial,no.,%2ys,RT,CT,%TRM,G3/4oes,patients,Gy/f,SOCCAR 2010,70,54,55/20,cis/vin,4,17%,Jeremic 1996,

35、65,43,69.6/58/6w carbo/etop,0,8,Belderbos 2006Fournel 2005Curran 2003Huber 2006Furuse 1999Zatloukal 2004Belani 2005Vokes 2004,66100201991565192182,3939373634.6343129,66/246

36、6/3360/3060/3056/28split60/3063/3466/33,daily ciscis/etopcis/vblwkly taxolcis/vindcis/vincarbo/taxcarbo/tax,1.510300.602?,17322513318

37、2831,Conclusions,Cancer Research UK & UCL Cancer Trials Centre,? 55Gy/20f/26-28d 同步順鉑聯(lián)合長春瑞賓治療III NSCLC, PS 0-1高度有效,? 2 year survival 同步放化療組> 50%,? 相比于16 RCTs, 1733 患者經(jīng)同步CTRT治療后的總生存最高且耐受性良好,,Randomized ph

38、ase II trial of uracil/tegafur (UFT) and cisplatinversus vinorelbine and cisplatin with concurrent thoracicradiotherapy for locally advanced unresectable stage III,non-small-cell lung cancer,NJLCG 0601,試驗(yàn)?zāi)繕?biāo),?尿嘧啶替加氟(

39、UFT)聯(lián)合順鉑(UP arm)對比長春瑞賓聯(lián)合順鉑輔以同步胸部放療,治療進(jìn)展期不可切除的stage III NSCLC 的有效性和安全性.,,? 首要終點(diǎn),整體有效率(ORR),? 次要終點(diǎn),Progression free survival (PFS)Overall survival (OS)Toxicity profile,RANDOMIZATIONStratified factor,AgeGenderHistology

40、Stage,59> /60~64/65~69/70~75Male/FemaleAdeno./Sq./Large/OthersIIIA/IIIB,ENROLLMENT,(n=70),UP arm (n=36)(35 patients were evaluable)UFT : 400mg/m2, day 1-14, 29-42CDDP : 80mg/m2, day 8, 36RT : 2Gy x 5days/we

41、ek, day 1-40, 60Gy,試驗(yàn)設(shè)計(jì),NP arm (n=34)(31 patients were evaluable)VNR : 20mg/m2, day 1, 8, 29, 36CDDP : 80mg/m2, day 1, 29RT : 2Gy x 5days/week, day 1-40, 60Gy,? 組織學(xué)或細(xì)胞學(xué)確診為NSCLC? 不可切除的 stage IIIA or IIIB disease

42、,? 無胸部放療，胸部外科手術(shù)和化療史,? ECOG 評分0 or 1? 年齡介于20 and 75 years,Patients Recruitment : Between February 2006 and May 2009,,反應(yīng)和生存數(shù)據(jù)毒性數(shù)據(jù)(≧Grade3),* Two patients died of radiation pneumonitis.,中位隨訪時(shí)間: 20.2 mo

43、nthsNCI-CTC ver. 3.0,Summery,ORRs 為80% and 71% 在UP 組 和NP 組.中位隨訪時(shí)間是20.2 months, median PFS 和中位生存在UP組是8.8months和26.9months，在NP組為6.8months和21.8months2-年生存率兩組分別是UP 51.0% ，NP 46.9%Grade 3/4 血液學(xué)毒性兩組分