局部晚期NSCLC放疗联合分子靶向治疗的研究进展

doi:10.3760/cma.j.issn.1004-4221.2016.12.021

Abstract
Figure/Table
References()
Related Citation (15)
Read Tracking
Download Tracking

Download: PDF (913 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS) Supporting Info

Abstract

Radiotherapy alone and chemoradiotherapy are main approaches for treating unresectable locally advanced non-small cell lung cancer (NSCLC). However, the overall efficacy of these treatment approaches is far from satisfactory. Recently, targeted molecular therapy has become a milestone in the treatment of locally advanced lung cancer. Particularly, inhibitors of epidermal endothelial growth factor and vascular endothelial growth factor have been widely used. Right now, more and more studies focus on radiotherapy combined with targeted molecular therapy for treating locally advanced NSCLC. According to the reported phaseⅠ-Ⅲ clinical trials, whether radiotherapy combined with targeted molecular therapy has better efficacy than concurrent chemoradiotherapy, sequential chemoradiotherapy, or radiotherapy alone still needs further studies. This paper provides a systematic analysis of radiotherapy combined with targeted molecular therapy for locally advanced NSCLC.

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	Fu Zhixue
	Liang Jun

Key words： Carcinoma,non-small cell lung/molecular targeted therapy Carcinoma,non-small cell lung/radiotherapy Research progress

Received: 01 August 2016

Corresponding Authors: Liang Jun,Email:liang23400@63.com

Cite this article:

Fu Zhixue,Liang Jun. Research advances in radiotherapy combined with targeted molecular therapy for locally advanced non-small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2016, 25(12): 1369-1374.

URL:

http://journal12.magtechjournal.com/Jweb_fszlx/EN/10.3760/cma.j.issn.1004-4221.2016.12.021 OR http://journal12.magtechjournal.com/Jweb_fszlx/EN/Y2016/V25/I12/1369

[1] American Cancer Society. Cancer facts and figures 2007[M].Atlanta:American Cancer Society,2007.
[2] Ciardiello F,Tortora G.EGFR antagonists in cancer treatment[J].N Engl J Med,2008,358(11):1160-1174.10.1056/NEJMra0707704.
[3] Dacic S,Flanagan M,Cieply K,et al. Significance of EGFR protein expression and gene amplification in non-small cell lung carcinoma[J].Am J Clin Pathol,2006,125(6):860-865.
[4] Ang KK,Bonner JA,Curran WJ,et al. The expanding role of EGFR-targeted therapies in NSCLC and head and neck cancer[M]Jackson:Skillman,American Academy of CME,2006:36.
[5] Meert AP,Martin B,Delmotte P,et al. The role of EGF-R expression on patient survival in lung cancer:a review with meta-analysis[J].Eur Respir J,2002,20(4):975-981.
[6] Ann KK,Andratschke N,Mlas L.Epidermal growth factor receptor and response of head-and-neck carcinoma to therapy[J].Int J Radiat Oncl Biol Phys,2004,58(3):959-965.
[7] Chinnaiyan P,Huang S,Vallabhaneni G,et al. Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva)[J].Cancer Res,2005,65(8):3328-3335.
[8] Prenzel N,Fischer OM,Streit S,et al. The epidermal growth factor receptor family as a central element for celltular signal transduction and diversification[J].Endocr Relat Cancer,2001,8(1):11-31.
[9] Cao C,Alber JM,Geng L,et al. Vascular endothelial growrth factor tyrosine-kinase inhibitor AZD2171 and fractionated radiotherapy in mouse models of lung cance[J].Cancer Res,2006,66(23):11409-11415.
[10] Shibuya K,Komaki R,Shintani T,et al. Targeted therapy against VERFR and EGFR with ZD6474 enhances the therapeutic efficacy of irradiation in an orthotopic models of human non-small-cell lung cancer[J].Int J Radiat Oncol Biol Phys,2007,69(5):1534-1543.
[11] Ready N,Janne P,Herndon J,et al. Chemoradiotherapy (CRT) and geftinib (G) in stage Ⅲ non-small cell lung cancer (NSCLC):a CALGB stratifed phase Ⅱ trial[J].J Clin Oncol,2006,24(Suppl 1):7046.
[12] Komaki R,Allen PK, Wei X,et al. Adding erlotinib to chemoradiation improves overall survival but not progression-free survival in stage Ⅲ non-small cell lung cancer[J].Int J Radiot Oncol Biol Phys,2015,92(2):317-324.10.1016/j.ijrobp.2015.02.005.
[13] Center B,Petty WJ,Ayala D,et al. A phase Ⅰstudy of gefitinib withconcurrent dose-escalated weekly docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel and maintenance gefitinib for patients with stage Ⅲ non-small cell lung cancer[J].J Torac Oncol,2010,5(1):69-74.10.1097/JTO.0b013e3181c59a0e.
[14] Choong NW,Mauer AM,Haraf DJ,et al. Phase Ⅰ trial of erlotinib-based multimodality therapy for inoperable stage Ⅲ non-small cell lung cancer[J].J Torac Oncol,2008,3(9):1003-1011.10.1097/JTO.0b013e31818396a4.
[15] Stinchcombe TE,Morris DE,Lee CB,et al. Induction chemotherapy with carboplatin,irinotecan,and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin,paclitaxel,and geftinib in unresectable stage Ⅲ_A and stage Ⅲ_B non-small cell lung cancer[J].J Torac Oncol,2008,3(3):250-257.10.1097/JTO.0b013e3181653cf4.
[16] Rothschild S,Bucher SE,Bernier J,et al. Geftinib in combination with irradiation with or without cisplatin in patients with inoperable stage Ⅲ non-small cell lung cancer:a phase Ⅰ trial[J].Int J Radiat Oncol Biol Phys,2011,80(1):126-132.10.1016/j.ijrobp.2010.01.048.
[17] Ramella S,Alberti AM,Cammilluzzi E,et al. Erlotinib and concurrent chemoradiation in pretreated NSCLC patients:radiobiological basis and clinical results[J].Biomed Res Int,2013,2013:403869.10.1155/2013/403869.
[18] Furuse K,Fukuoka M,Kawahara M,et al. Phase Ⅲ study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin,vindesine,and cisplatin in unresectable stage Ⅲ non-small-cell lung cancer[J].J Clin Oncol,1999,17(9):2692-2699.
[19] Curran Jr WJ,Paulus R,Langer CJ,et al. Sequential vs. Concurrent chemoradiation for stage Ⅲ non-small cell lung cancer:randomized phase Ⅲ trial RTOG 9410[J].J Natl Cancer Inst,2011,103(19):1452-1460.10.1093/jnci/djr325.
[20] Fournel P,Robinet G,Thomas P,et al. Randomized phase Ⅲ trial of sequential chemoradiotherapy compared with concurrent chemoradio-therapy in locally advanced non-small-cell lung cancer:Groupe Lyon-Saint-Etienne d′Oncologie Thoracique-Groupe Francais de Pneumo-Cancerologie NPC 95-01 study[J].J Clin Oncol,2005,23(25):5910-5917.
[21] Gervais R,Ducolone A,Lechevalier T,et al. Conventional radiation (RT) with daily carboplatin (Cb) compared to RT alone after induction chemotherapy (ICT)[vinorelbine (Vr)-cisplatine (P)]:final results of a randomized phase Ⅲ trial in stage Ⅲ unresectable non small cell lung (NSCLC) cancer. Study CRG/BMS/NPC/96 of the French Lung Cancer Study Group FNCLCC and IFCT[J].Proc Am Soc Clin Oncol,2005,23:7016.
[22] Zatloukal P,Petruzelka L,Zemanova M,et al. Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer:a randomized study[J].Lung Cancer,2004,46(1):87-98.
[23] Huber RM,Flentje M,Schmidt M,et al. Simultaneous chemoradiotherapy compared with radiotherapy alone after induction chemotherapy in N.Bi and L.Wang 130 inoperable stage Ⅲ_A or Ⅲ_B non-small cell lung cancer:Study CTRT99/97 by the Bronchial Carcinoma Therapy Group[J].J Clin Oncol,2006,24(27):4397-4404.
[24] Clamon G,Herndon J,Cooper R,et al. Radiosensitization with carboplatin for patients with unresectable stage Ⅲ non-small-cell lung cancer:a phase Ⅲ trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group[J].J Clin Oncol,1999,17(1):4-11.
[25] Belderbos J,Uitterhoeve L,van Zandwijk N,et al. Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973)[J].Eur J Cancer,2007,43(1):114-121.
[26] Ahn JS,Ahn YC,Kim JH,et al. Multinational randomized phase Ⅲ trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage Ⅲ non-small-cell lung cancer:KCSG-LU05-04[J].J Clin Oncol,2015,33(24):2660-2666.10.1200/JCO.2014.60.0130.
[27] Senan S,Brade A,Wang LH,et al. PROCLAIM:randomized phase Ⅲ trial of pemetrexed-cisplatin or etoposide-cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer[J].J Clin Oncol,2016,34(9):953-962.10.1200/JCO.2015.64.8824.
[28] Lilenbaum R,Samuels M,Wang X,et al. A phaseⅡstudy of induction chemotherapy followed by thoracic radiotherapy and erlotinib in poor-risk stage Ⅲ non-small-cell lung cancer:results of CALGB 30605(Alliance)/RTOG 0972(NRG)[J].J Thorac Oncol,2015,10(1):143-147.10.1097/JTO.0000000000000347.
[29] Niho S,Ohe Y,Ishikura S,et al. Induction chemotherapy followed by gefitinib and concurrent thoracic radiotherapy for unresectable locally advanced adenocarcinoma of the lung:a multicenter feasibility study (JCOG 0402)[J].Ann Oncol, 2012,23(9):2253-2258.10.1093/annonc/mds012.
[30] Martínez E, Martínez M, Rico M,et al. Feasibility,tolerability,and effcacy of heconcurrent addition of erlotinib to thoracic radiotherapy in locally advanced unresectable non-small-cell lung cancer:a phase Ⅱ trial[J].Onco Targets Ther, 2016,9:1057-1066.10.2147/OTT.S89755. eCollection 2016.
[31] Martinez E,Martinez M,Violas N,et al. Feasibility and tolerability of the addition of erlotinib to 3D thoracic ra-diotherapy (RT) in patients (p) with unresectable NSCLC:a prospective randomized phase Ⅱ study[J].J Clin Oncol,2008, 26:abstr.7563.
[32] Swaminath A, Wright JR, Tsakiridis TK,et al. A phase Ⅱ trial of erlotinib and concurrent palliative thoracic radiation for patients with non-small-cell lung cancer[J].Clini Lung Cancer.2016 Mar;17(2):142-9. 10.1016/j.cllc.2015.09.008.
[33] Okamoto I,Takahashi T,Okamoto H,et al. Single-agent gefitinib with concurrent radiotherapy for locally advanced non-small cell lung cancer harboring mutations of the epidermal growth factor receptor[J].Lung Cancer,2011,72(2):199-204.10.1016/j.lungcan.2010.08.016.
[34] Zhuang H, Yuan Z, Chang JY,et al. Radiation pneumonitis in patients with non-small-cell lung cancer treated with erlotinib concurrent with thoracic radiotherapy[J].J Thorac Oncol,2014,9(6):882-885.10.1097/JTO.0000000000000126.
[35] Ren S,Li Y,Li W,et al. Fatal asymmetric interstitial lung disease after erlotinib for lung cancer[J].Respiration,2012,84(5):431-435.10.1159/000339508.
[36] Tsubata Y,Hamada A,Sutani A,et al. Erlotinib-induced acute interstitial lung disease associated with extreme elevation of the plasma concentration in an elderly non-small-cell lung cancer patient[J].J Cancer Res Ther,2012,8(1):154-156.10.4103/0973-1482.95201.
[37] Nanda A,Dias-Santagata DC,Stubbs H,et al. Unusual tumor response and toxicity from radiation and concurrent erlotinib for non-small-cell lung cancer[J].Clin Lung Cancer,2008,9(5):285-287.10.3816/CLC.2008.n.044.
[38] Chang CC,Chi KH,Kao SJ,et al. Upfront geftinib/erlotinib treatment followed by concomitant radiotherapy for advanced lung cancer:a mono-institutional experience[J].Lung Cancer,2011,73(2):189-194.10.1016/j.lungcan.2010.12.007.
[39] Blumenschein GR Jr,Paulus R,Curran WJ,et al. Phase Ⅱ study of cetuximab in combination with chemoradiation in patients with stage Ⅲ_A/B non-small-cell lung cancer:RTOG 0324[J].J Clin Oncol,2011,29(17):2312-2318.10.1200/JCO.2010.31.7875.
[40] Govindan R,Bogart J,Stinchcombe T,et al. Randomized phase Ⅱ study of pemetrexed,carboplatin,and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer:Cancer and Leukemia Group B Trial 30407[J].J Clin Oncol,2011,29(23):3120-3125.10.1200/JCO.2010.33.4979.
[41] Bradley JD,Paulus R,Komaki R,et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage Ⅲ_A or Ⅲ_B non-small-cell lung cancer (RTOG 0617):a randomised,two-by-two factorial phase 3 study[J].Lancet Oncol,2015,16(2):187-199.10.1016/S1470-2045(14)71207-0.
[42] Jensen AD,Münter MW,Bischoff HG,et al. Combined treatment of nonsmall cell lung cancer stage Ⅲ with intensity-modulated radiotherapy and cetuximab:The NEAR trial[J].Cancer,2011,117(13):2986-2994.10.1002/cncr.25888.
[43] Jatoi A,Schild SE,Foster N,et al. A phase Ⅱ study of cetuximab and radiation in elderly and/or poor performance status patients with locally advanced non-small-cell lung cancer (N0422)[J].Ann Oncol,2010,21(10):2040-2044.10.1093/annonc/mdq075.
[44] Hallqvist A,Wagenius G,Rylander H,et al. Concurrent cetuximab and radiotherapy after docetaxel-cisplatin induction chemotherapy in stage Ⅲ NSCLC:satellite-A phase Ⅱ study from the Swedish Lung Cancer Study Group[J].Lung Cancer,2011,71(2):166-172.10.1016/j.lungcan.2010.05.011.
[45] Chen Y,Moon J,Pandya KJ,et al. A pilot study (SWOG S0429) of weekly cetuximab and chest radiotherapy for poor-risk stage Ⅲ non-small cell lung cancer[J].Front Oncol,2013,3:219.10.3389/fonc.2013.00219.
[46] Hughes S,Liong J,Miah A,et al. A brief report on the safety study of induction chemotherapy followed by synchronous radiotherapy and cetuximab in stage Ⅲ non-small cell lung cancer (NSCLC):SCRATCH study[J].J Thorac Oncol,2008,3(6):648-651.10.1097/JTO.0b013e3181757a60.
[47] Spigel DR,Hainsworth JD,Yardley DA,et al. Tracheoesophageal fi stula formation in patients with lung cancer treated with chemoradiation and bevacizumab[J].J Clin Oncol,2010,28(1):43-48.10.1200/ JCO.2009.24.7353.
[48] Socinski MA,Stinchcombe TE,Moore DT,et al. Incorporat ing bevacizumab and erlotinib in the combined-modality treatment of stage Ⅲ non-smal l-cell lung cancer:results of a phase Ⅰ/ Ⅱ trial[J].J Clin Oncol,2012,30(32):3953-3959.10.1200/ JCO.2012.41.9820.
[49] Milas L,Kishi K,Hunter N,et al. Enhancement of tumor response to gamma-radiation by an inhibitor of cylcooxygenase-2 enzyme[J].J Natl Cancer Inst,1999,91(17):1501-1504.
[50] Kishi K,Petersen S,Petersen C,et al. Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor[J].Cancer Res,2000,60(5):1326-1331.
[51] Gore E,Bae K,Langer C,et al. Phase Ⅰ/Ⅱ trial of a COX-2 inhibitor with limited field radiation for intermediate prognosis patients who have locally advanced non-small-cell lung cancer:Radiation Therapy Oncology Group 0213[J].Clin Lung Cancer,2011,12(2):125-130.10.1016/j.cllc.2011.03.007.
[52] Edelman MJ,Burrows W,Krasna MJ,et al. Phase Ⅰ trial of carboplatin/paclitaxel/bortezomib and concurrent radiotherapy followed by surgical resection in stage Ⅲ non-small cell lung cancer[J].Lung Cancer,2010,68(1):84-88.10.1016/j.lungcan.2009.05.003.
[53] Sarkaria JN,Schwingler P,Schild SE,et al. Phase Ⅰ trial of sirolimus combined with radiation and cisplatin in nonsmall cell lung cancer[J].J Thorac Oncol,2007,2(8):751-757.