肺癌同步放化療進展

1、同步放化療在NSCLC的進展,,主要內容,放療在早期NSCLC的進展同步放化療與靶向藥物治療NSCLC的進展同步放化療聯(lián)合培美曲塞治療NSCLC的研究進展同步放化療在晚期NSCLC的進展,放療在早期NSCLC的進展同步放化療與靶向藥物治療NSCLC的進展同步放化療聯(lián)合培美曲塞治療NSCLC的研究進展同步放化療在晚期NSCLC的進展,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的I期非小細胞肺癌患者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,,,不選擇手術的原因,SABR對潛在科手術病人的基線特征,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的(N=94)?并發(fā)其他腫瘤的(N=50)?因主要共患病除外手術的, 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), 腫瘤未達縱膈和胸壁–3 x 18 Gy @80%; 3 fx/week (BED 134 Gy)T1 tumors 達胸壁和縱膈, 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例潛在可手術患者的結果,結論,應用SABR是可行的治療后30天死亡率為0%，對比該群患者術后死亡率為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年鼓勵內鏡分期[Nakajima T, 2010; Harley D, 2010]SABR數(shù)據(jù)支持隨機入組,,放療在早期NSCLC的進展同步放化療與靶向藥物治療NSCLC的進展同步放化療聯(lián)合培美曲塞治療

6、NSCLC的研究進展同步放化療在晚期NSCLC的進展,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,實驗設計,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個病人且大于等于3級的毒性統(tǒng)計,反應率–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 生存結果,首要終點是PFS –假設檢驗= PFS at 1 year = 50%排除值if PFS > 70%,LCCC高劑量同步放化療的相關臨床實驗,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-結論,誘導CbP + Bev 是可以耐受并有效的同步Erlotinib + Bev 繼之以強烈的同步放化療治療非鱗癌的NSCLC 的前提是 ….放療參數(shù)要預期設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 的結果相對于我們的歷史經(jīng)驗不被看好基于實驗中觀察到得毒性加倍, 應用Bev 和chemoRT 不被推薦,MultimodAlity treatment with Radio-chemoTherapy and Erlotinib in advanced NSCLC (MARTE trial)進展期NSCLC放

16、化療聯(lián)合厄羅替尼的多模式治療（MARTE實驗）,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, 標準分割(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毒性,病人基線特征和毒性統(tǒng)計數(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,,,結論,臨床前期數(shù)據(jù)證實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標志物保障了放射治療的效應,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),測定標放療準計量的西妥昔單抗聯(lián)合同步個體化，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個月后經(jīng)FDG-PET測定代謝反應 (N=22) ? CR:8 ? PR:11 ? PD:3結論 ?

22、同步放化療聯(lián)合順鉑，長春瑞賓及西妥昔單抗時可行的 ?長春瑞賓不能選擇最大劑量 ?毒性在預期內 ?3月后治療結果令人鼓舞,,放療在早期NSCLC的進展同步放化療與靶向藥物治療NSCLC的進展同步放化療聯(lián)合培美曲塞治療NSCLC的研究進展同步放化療在晚期NSCLC的進展,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：研究設計,摘要e18502：研究結果 – 緩解情況,摘要e18502：研究結果 – 不良反應,放療在早期NSCLC的進展同步放化療與靶向藥物治療NSCLC的進展同步放化療聯(lián)合培美曲塞治療NSCLC的研究進展同步放化療在晚期NSCLC的進展,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：三周期EP誘導化療繼以同步放化療聯(lián)合手術治療的一項15

26、年長期生存和競爭風險分析,試驗設計,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,結論,LTS/VLTSon

27、theWGCC-trialJCO98定義為第一個選擇性可切除IIIA期NSCLC患者的隨機對照多中心臨床試驗探索性分析顯示前期治療對15年長期結果無影響基于選擇性的R0-可切除的IIIA和IIIB期患者繼以誘導治療手長期隨訪結果優(yōu)60個月的競爭性風險分析提示(心血管，肺疾病，再發(fā)肺癌和再發(fā)腫瘤是香港風險 (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,試驗目標,?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,治療進展期不可切除的stage III NSCLC 的有效性和安全性.,,? 首要終點,整體有效率(ORR),? 次要終點,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,試驗設計,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,? 組織學或細胞學確診為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 血液學毒性兩組分