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2 肺癌診療指引 106 : NSCLC-1~3 1. pstage IA (+) / 2. pstage IB (+) / 3. pstage II (+) / 4. pstageiv ECOG PS /EGFR(+) NSCLC-2 1. T3,N0(invasion) / / 2. T4 extensive,n0-1 / / NSCLC-2 1. T1-3,N3/T4,N2-3 / NSCLC-4 M1 a-b NSCLC-1~3 1. pstage IA (+) 2. pstage IB ( ) (+). 3. pstage II (+). 4.pstageIV 1. ECOG PS ( ) 2. NSCLC-2 1. T3,N0(invasion) 2. T4 extensive,n0-1 NSCLC-3 1. T1-3,N3/T4,N2-3 NSCLC-4 M1 a-c NSCLC-4 1. (PDL-1) 癌症診療指引34

3 小細胞肺癌診療指引共識1-1 ( ECOG) ( ) (CEA) (,EBUS ct1-2,n0 ct1-2,n0 ECOG PS(0-2) / ECOG PS(3-4) ECOG PS(0-2) ECOG PS(3-4) (1) ( ) (2) (+) 癌症診療指引35

4 小細胞肺癌診療指引共識2-2 ( ECOG) ( ) (CEA) (,EBUS 癌症診療指引36

5 非小細胞肺癌診療指引共識1-1 ( ECOG) ( ) CEA ( ) SCC ( (,EBUS Cyfra 21-1 T1-2,N0 T1-2,N1 / : (SABR)/ (RFA)/ (cryotherapy) 1: Medically Inoperable 2: Chest wall, proximal airway, or mediastinum 3: Superior sulcus tumor 4: pstage IA pstage IB pstage II pstage III A pstage III B pstage IV (1) ( ) (2) (+) (1) ( ) (2) (+) (1) ( ) (2) (+) (1) ( ) N 0, N 1 : N 2 : + (2) (+) 4 1. ECOG PS ( ) 2. 癌症診療指引37

6 非小細胞肺癌診療指引共識2-2 ( ECOG) ( ) CEA ( ) SCC ( (,EBUS Cyfra 21-1 T3,N0 ( invasion) T3,N1 T4 extension, N : Medically Inoperable 2: Chest wall, proximal airway, or mediastinum 3: Superior sulcus tumor 4: pstage IA pstage IB pstage II pstage III A pstage III B pstage IV (1) ( ) (2) (+) (1) ( ) (2) (+) 4 (1) ( ) (2) (+) 4 (1) ( ) N 0, N 1 : N 2 : + (2) (+) 4 1. ECOG PS ( ) 2. 癌症診療指引38

7 非小細胞肺癌診療指引共識3-3 ( ECOG) ( ) CEA ( ) SCC ( T1-3,N2 T1-3,N3 T4,N2-3 pstage IA pstage IB pstage II pstage III A (1) ( ) (2) (+) (1) ( ) (2) (+) 4 (1) ( ) (2) (+) / 4 (1) ( ) N 0, N 1 : N 2 : + (2) (+) 4 癌症診療指引39 (,EBUS Cyfra : Medically Inoperable 2: Chest wall, proximal airway, or mediastinum 3: Superior sulcus tumor 4: pstage III B pstage IV 1. ECOG PS ( ) 2.

8 非小細胞肺癌診療指引共識4-4 ( ECOG) ( ) CEA ( ) SCC ( (EGFR) (,EBUS Cyfra 21-1 (ALK,ROS-1) PDL-1 M1a-c / 癌症診療指引40

9 肺癌追蹤流程 ( ) ( ) 3-4 ( )/ / 6 ( )/ / ( ) 3, 6 / / 6 / / 12 / / 癌症診療指引41

10 肺癌診療指引參考文獻 1. NCCN Clinical Practice in Oncology:Small Cell Lung Cancer V NCCN Clinical Practice in Oncology:Non-Small Cell Lung Cancer V Takada M, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study J Clin Oncol. 2002;15;20(14): Sundstrøm S, Bremnes RM, Kaasa S, et al. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002;15;20(24): Rossi A, Di Maio M, Chiodini P, et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol ;10;30(14): Pavel ME, Hainsworth JD, Baudin E, et al. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet ;10;378(9808): Sholl LM, Xiao Y, Joshi V, et al. EGFR mutation is a better predictor of response to tyrosine kinase inhibitors in non-small cell lung carcinoma than FISH, CISH, and immunohistochemistry. Am J Clin Pathol. 2010;133(6): Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11(2): Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;24;362(25): Song WA, Zhou NK, Wang W, et al. Survival benefit of neoadjuvant chemotherapy in non-small cell lung cancer: an updated meta-analysis of 13 randomized control trials. J Thorac Oncol. 2010;5(4): Shah AA, Berry MF, Tzao C, et al. Induction chemoradiation is not superior to induction chemotherapy alone in stage IIIA lung cancer. Ann Thorac Surg. 2012;93(6): 癌症診療指引42

11 肺癌診療指引參考文獻 12. Kappers I, van Sandick JW, Burgers SA, et al. Surgery after induction chemotherapy in stage IIIA-N2 non-small cell lung cancer: why pneumonectomy should be avoided. Lung Cancer. 2010;68(2): 癌症診療指引43

12 癌症診療指引44 Small Cell Lung Cancer Chemotherapy as primary or adjuvant therapy Limited Stage (maximum of 4-6 cycles): During chemotherapy + RT, cisplatin/etoposide is recommended The use of myeloid growth factors is not recommended during mg/m 2 Cisplatin Q3W 4-6 1, 2 Etoposide Q3W 4-6 mg/m 2 Carboplatin 5-6 AUC 1 Q3W Etoposide Q3W 4-6 Extensive Stage (maximum of 4-6 cycles): mg/m 2 Cisplatin Q3W 4-6 4, 5 Etoposide Q3W 4-6 mg/m 2 Carboplatin 5-6 AUC 1 Q3W Etoposide Q3W 4-6

13 Chemotherapy: Subsequent 癌症診療指引45 Clinical trial preferred. Relapse <6 months, PS 0-2: mg/m 2 Topotecan Q3W 7 mg/m 2 Topotecan 2.3 PO 1-5 Q3W 8 mg/m 2 Cyclophosphamide Q3W 7 Doxorubicin 45 1 Q3W Vincristine 2 1 Q3W mg/m 2 Nivolumab 3 mg/kg 1 Q2W 9 mg/m 2 Nivolumab 3 mg/kg 1 Q2W 9 Ipilimumab 1 mg/kg 1 Q2W 1. Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999;340(4):

14 Saito H, Takada Y, Ichinose Y, et al. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy 2. 癌症診療指引46 followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group J Clin Oncol 2006;24(33): Skarlos DV, Samantas E, Briassoulis E, et al. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol 2001;12(9): Spigel R, Townley PM, Waterhouse DM, et al. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol 2011;29: Niell HB, Herndon JE, Miller AA, et al. Randomized phase III Intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte-colony stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B trial J Clin Oncol 2005;23: Okamoto H, Watanabe K, Nishiwaki Y, et al. Phase II study of area under the plasmaconcentration-versus-time curvebased carboplatin plus standard-dose intravenous etoposide in elderly patients with small cell lung cancer. J Clin Oncol 1999;17(11): von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999;17(2): O'Brien ME, Ciuleanu TE, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006;24: Atonia SJ, Lopez-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol 2016;17:

15 Cell Lung Cancer Non-Small 癌症診療指引47 Neoadjuvant and Adjuvant therapy mg/m 2 Cisplatin Q3W Vinorelbine , 8 Q3W 4 mg/m 2 Cisplatin Q3W 4 19 Vinorelbine , 8 Q3W 4 mg/m 2 Cisplatin Q3W 4 4 Gemcitabine , 8 Q3W 4 mg/m 2 Cisplatin Q3W 4 5 Docetaxel Q3W 4 mg/m 2 Cisplatin Q3W 4 6 Pemetrexed Q3W 4 mg/m 2 UFUR 200 PO BID/TID 20

16 mg/m2 癌症診療指引48 Carboplatin 5 AUC 1 Q3W 4 12 Pemetrexed Q3W 4 mg/m 2 Carboplatin 5 AUC 1 Q3W 4 13 Gemcitabine , 8 Q3W 4 mg/m 2 Carboplatin 6 AUC 1 Q3W 4 14 Paclitaxel Q3W 4 Chemotherapy regimens used with radiation therapy Concurrent chemotherapy/rt regimens Regimens can be used as neoadjuvant/preoperative/induction chemoradiotherapy Regimens can be used as adjuvant or definitive concurrent chemotherapy/rt mg/m 2 Ciaplatin 50 1, 8 Q4W 2 7, 8 Etoposide 50mg PO BID 1, 2, 5, 6 QW 10

17 mg/m2 癌症診療指引49 Carboplatin 5 AUC 1 Q3W 4 9 Pemetrexed Q3W 4 mg/m 2 Cisplatin 75 1 Q3W 3 10 Pemetrexed Q3W (additional) mg/m 2 Paclitaxel QW 11 Carboplatin 2 AUC 1 QW Paclitaxel Q3W 2 (additional) Carboplatin 6 AUC 1 Q3W 2 (additional) Sequential Chemotherapy/RT Regimens (Adjuvant): As all the neoadjuvant/adjuvant chemotherapy regimens Target Therapy EGFR-mutation-positive mg/m 2 Erotinib 150 mg QD AC 15 mg/m 2 Afatinib 40 mg QD AC 16

18 mg/m2 癌症診療指引50 Gefitinib 250 mg QD 17 ALK positive mg/m 2 Crizotinib 250 mg BID Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-lung cancer. N Engl J Med 2005;352: Arriagada R, Bergman B, Dunant A, et al. The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med 2004;350: Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol 2006;7: Pérol M, Chouaid C, Pérol D, et al. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-smallcell lung cancer. J Clin Oncol 2012;30: Fossella F, Pereira JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2003;21: Kreuter M, Vansteenkiste J, Fishcer JR, et al. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol 2013;24:

19 Albain KS, Crowley JJ, Turrisi AT III, et al. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non- 7. 癌症診療指引51 small-cell lung cancer: A Southwest Oncology Group Phase II Study, SWOG J Clin Oncol 2002;20: Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG J Natl Cancer Inst. 2011;103: 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 J Clin Oncol 2011;29: Choy H, Gerber DE, Bradley JD, et al. Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: a systematic review of completed and ongoing studies. Lung Cancer 2015;87: Bradley JD, Paulus R, Komaki R, et al. Standard-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomized, two-by-two factorial phase 3 study. Lancet Oncol 2015;16: Zhang L, Ou W, Liu Q, et al. Pemetrexed plus carboplatin as adjuvant chemotherapy in patients with curative resected nonsquamous non-small cell lung cancer. Thoracic Cancer. 2014;5(1): Usami N, Yokoi K, Hasegawa Y, et al. Phase II study of carboplatin and gemcitabine as adjuvant chemotherapy in patients with completely resected non-small cell lung cancer: a report from the Central Japan Lung Study Group, CJLSG 0503 trial. Int J Clin Oncol. 2010;15(6): Strauss GM, Herndon JE, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB nonsmall-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008;26(31): Product Information: TARCEVA(R) oral tablets, erlotinib oral tablets. OSI Pharmaceuticals, LLC (per FDA), Farmingdale, NY, Product Information: GILOTRIF(TM) oral tablets, afatinib oral tablets. Boehringer Ingelheim Pharmaceuticals, Inc. (per FDA), Ridgefield, CT, Product Information: IRESSA(R) oral tablets, gefitinib oral tablets. AstraZeneca Pharmaceuticals (per FDA), Wilmington, DE, 2015.

20 19. NCCN, [NSCL-D]. Non-small cell lung cancer, version 9, Product Information: UFUR Capsule. tegafur, uracil oral capsules Product Information: XALKORI(R) oral capsules, crizotinib oral capsules. Pfizer Labs (per FDA), New York, NY, 癌症診療指引52

21 Therapy for Advanced or Metastatic Disease of NSCLC Systemic 癌症診療指引53 First-line systemic therapy options Adenocarcinoma, large cell, NSCLC NOS (PS 0-1) mg/m 2 Bevacizumab 15 mg/kg 1 Q3W 6 1 Carboplatin 6 AUC 1 Q3W Paclitaxel Q3W mg/m 2 Bevacizumab 15 mg/kg 1 Q3W 4 2 Carboplatin 6 AUC 1 Q3W Pemetrexed Q3W mg/m 2 Bevacizumab 15 mg/kg 1 Q3W 4 3 Cisplatin 75 1 Q3W Pemetrexed Q3W mg/m 2 Carboplatin 6 AUC 1 Q3W 6 4 Albumin-Paclitaxel 100 1, 8, 15 Q3W

22 mg/m2 癌症診療指引54 Carboplatin 6 AUC Q3W 5 Docetaxel 75 Q3W mg/m 2 Carboplatin 4-5 AUC 1 Q4W 7 Etoposide 50mg PO BID 1-14 or 1-21 Q4W mg/m 2 Carboplatin 5 AUC 1 Q4W 4 8 Gemcitabine , 8, 15 Q4W 4 mg/m 2 Carboplatin 6 AUC 1 Q3W 9 Paclitaxel Q3W mg/m 2 Carboplatin 6 AUC 1 Q3W 6 10 Pemetrexed Q3W 6

23 mg/m2 癌症診療指引55 Cisplatin 75 1 Q3W 5 Docetaxel 75 1 Q3W mg/m 2 Cisplatin Q3W 11 Etoposide Q3W mg/m 2 Cisplatin 80 1 Q3W 9 Gemcitabine , 8 Q3W mg/m 2 Cisplatin 75 1 Q3W 6 12 Gemcitabine , 8 Q3W 6 mg/m 2 Paclitaxel Q3W 13 Cisplatin 75 2 Q3W mg/m 2 Cisplatin 75 1 Q3W 12 Pemetrexed Q3W

24 mg/m2 癌症診療指引56 Gemcitabine , 8 Q3W 8 14 Docetaxel 85 8 Q3W 8 mg/m 2 Gemcitabine , 8 Q3W 6 15 Vinorelbine 25 1, 8 Q3W 6 mg/m 2 Pembrolizumab 2 mg/kg 1 Q3W 4 28 Carboplatin 5 AUC 1 Q3W 4 Pemetrexed Q3W 4 Adenocarcinoma, large cell, NSCLC NOS (PS 2) mg/m 2 Albumin-Paclitaxel Q3W 16 mg/m 2 Albumin-Paclitaxel 100 1, 8, 15 Q4W 17 mg/m 2 Carboplatin 6 AUC 1 Q3W 6 18 Albumin-Paclitaxel 100 1, 8, 15 Q3W 6

25 mg/m2 癌症診療指引57 Carboplatin 6 AUC 1 Q3W 5 Docetaxel 75 1 Q3W mg/m 2 Carboplatin Etoposide mg/m 2 Carboplatin 4-5 AUC 1 Q4W 7 Etoposide or 1-21 Q4W mg/m 2 Carboplatin 5 AUC 1 Q4W 4 8 Gemcitabine , 8, 15 Q4W mg/m 2 Carboplatin 6 AUC 1 Q3W 9 Paclitaxel Q3W mg/m 2 Carboplatin 6 AUC 1 Q3W 6 10 Pemetrexed Q3W

26 mg/m2 癌症診療指引58 Docetaxel 75 1 Q3W 6 19, 20 mg/m 2 Gemcitabine , 8, 15 Q4W 9 21 mg/m 2 Gemcitabine , 8 Q3W 6 22, 23 mg/m 2 Gemcitabine , 8 Q3W 8 14 Docetaxel 85 8 Q3W 8 mg/m 2 Gemcitabine , 8 Q3W 6 15 Vinorelbine 25 1, 8 Q3W 6 mg/m 2 Paclitaxel Q3W 6 24 mg/m 2 Paclitaxel 80 1, 8, 15 Q4W 4 25, 26

27 mg/m2 癌症診療指引59 Pemetrexed Q3W Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small lung cancer. N Engl J Med 2006;355: Patel JD, Socinski MA, Garon EB, et al. Pointbreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small cell lung cancer. J Clin Oncol 2013;31: Barlesi F, Scherpereel A, Rittmeywr A, et al. Randomized phase III trial of maintence bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrxed in advanced nonsquamous non-small cell lung cancer: AVAPERL. J Clin Onco 2013;31: Socinski MA1, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol 2012;30: Fossella F, Periera JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2003;21(16): Klastersky J, Sculier JP, Lacroix H, et al. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol J Clin Oncol 1990;8: Frasci G, Comella P, Panza N, et al. Carboplatin-oral etoposide personalized dosing in elderly non-small cell lung cancer patients. Gruppo Oncologico Cooperativo Sud-Italia. Eur J Cancer. 1998;34: Danson S, Middleton MR, O'Byrne KJ, et al. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003;98:

28 Ohe Y, Ohashi Y, Kubota K, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, 9. 癌症診療指引60 cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced nonsmall-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol 2007;18: Scagliotti GV, Kortsik C, Dark GG, et al. Pemetrexed combined with oxaliplatin or carboplatin as first-line treatment in advanced non-small cell lung cancer: a multicenter, randomized, phase II trial. Clin Cancer Res. 2005;11: Cardenal F, Lopez-Cabrerizo MP, Anton A, et al. Randomized phase III study of gemcitabine-cisplatin versus etoposidecisplatin in the treatment of locally advanced or metastatic non-small cell lung cancer. J Clin Oncol 1999;17: Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage NSCLC. J Clin Oncol 2008;26: Schiller JH, Harrington D, Belani CP, et al. Comparison of Four Chemotherapy Regimens for Advanced Non Small-Cell Lung Cancer. N Engl J Med 2002; 346: Pujol JL, Breton JL, Gervais R, et al. Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-smallcell lung cancer: a phase III study addressing the case for cisplatin. Ann Oncol 2005;16: Tan EH, Szczesna A, Krzakowski M, et al. Randomized study of vinorelbine--gemcitabine versus vinorelbine--carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2005;49: Green MR, Manikhas GM, Orlov S, et al. Abraxane, a novel Cremophor -free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Ann Oncol. 2006;17: Rizvi NA, Riely GJ, Azzoli CG, et al. Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 2008;26: Socinski MA1, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol 2012;30: Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small cell lung cancer previously treated with platinumcontaining chemotherapy regimens. The TAX 320

29 Cell Lung Cancer Study Group. J Clin Oncol 2000;18: Non-Small 癌症診療指引 Fidias PM, Dakhil SR, Lyss AP, et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2009;27: Zatloukal P, Kanitz E, Magyar P, Jassem J, et al. Gemcitabine in locally advanced and metastatic non-small cell lung cancer: the Central European phase II study. Lung Cancer. 1998;22: Sederholm C, Hillerdal G, Lamberg K, et al. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005;23: Pérol M, Chouaid C, Pérol D, et al. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-smallcell lung cancer. J Clin Oncol. 2012;30: Lilenbaum RC, Herndon JE 2nd, List MA, et al. Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730).J Clin Oncol. 2005;23: Ceresoli GL, Gregorc V, Cordio S, et al. Phase II study of weekly paclitaxel as second-line therapy in patients with advanced non-small cell lung cancer. Lung Cancer. 2004;44: Yasuda K, Igishi T, Kawasaki Y, et al. Phase II study of weekly paclitaxel in patients with non-small cell lung cancer who have failed previous treatments. Oncology. 2004;66: Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with nonsmall-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22: Langer CJ, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. The Lancet Oncology. 2016;17:

30 cell carcinoma (PS 0-1) Squamous 癌症診療指引62 mg/m 2 Carboplatin 6 AUC 1 Q3W 13 Albumin-Paclitaxel 100 1, 8, 15 Q3W mg/m 2 Carboplatin 6 AUC 1 Q3W 1 Docetaxel 75 1 Q3W mg/m 2 Carboplatin 5 AUC 1 Q4W 4 Gemcitabine , 8, 15 Q4W mg/m 2 Paclitaxel Q3W 5 Carboplatin 6 AUC 1 Q3W mg/m 2 Docetaxel 75 1 Q3W 1 Cisplatin 75 1 Q3W

31 mg/m2 癌症診療指引63 Cisplatin Q3W 6 Etoposide Q3W mg/m 2 Cisplatin 80 1 Q3W 5 Gemcitabine , 8 Q3W mg/m 2 Cisplatin 75 1 Q3W 7 Gemcitabine , 8 Q3W mg/m 2 Paclitaxel Q3W 8 Cisplatin 75 2 Q3W mg/m 2 Gemcitabine , 8 Q3W 9 Docetaxel 85 8 Q3W mg/m 2 Gemcitabine , 8 Q3W 10 Vinorelbine 25 1, 8 Q3W

32 cell carcinoma (PS 2) Squamous 癌症診療指引64 mg/m 2 Albumin-Paclitaxel Q3W 11 mg/m 2 Carboplatin 6 AUC 1 Q3W 12, 13 Albumin-Paclitaxel 100 1, 8, 15 Q3W mg/m 2 Carboplatin 6 AUC 1 Q3W 1 Docetaxel 75 1 Q3W mg/m 2 Carboplatin Etoposide mg/m 2 Carboplatin 4-5 AUC 1 Q4W 3 Etoposide or 1-21 Q4W mg/m 2 Carboplatin 5 AUC 1 Q4W 4 Gemcitabine , 8, 15 Q4W

33 mg/m2 癌症診療指引65 Carboplatin 6 AUC 1 Q3W 5 Paclitaxel Q3W mg/m 2 Docetaxel 75 1 Q3W 14, 15 mg/m 2 Gemcitabine , 8, 15 Q4W 16 mg/m 2 Gemcitabine , 8 Q3W 17, 18 mg/m 2 Gemcitabine , 8 Q3W 9 Docetaxel 85 8 Q3W mg/m 2 Gemcitabine , 8 Q3W 10 Vinorelbine 25 1, 8 Q3W mg/m 2 Paclitaxel Q3W 19

34 mg/m2 癌症診療指引66 Paclitaxel 80 1, 8, 15 Q4W 20, Fossella F, Periera JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2003;21(16): Klastersky J, Sculier JP, Lacroix H, et al. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol J Clin Oncol 1990;8: Frasci G, Comella P, Panza N, et al. Carboplatin-oral etoposide personalized dosing in elderly non-small cell lung cancer patients. Gruppo Oncologico Cooperativo Sud-Italia. Eur J Cancer. 1998;34: Danson S, Middleton MR, O'Byrne KJ, et al. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003;98: Ohe Y, Ohashi Y, Kubota K, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol 2007;18: Cardenal F, Lopez-Cabrerizo MP, Anton A, et al. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small cell lung cancer. J Clin Oncol 1999;17: Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage NSCLC. J Clin Oncol 2008;26: Schiller JH, Harrington D, Belani CP, et al. Comparison of Four Chemotherapy Regimens for Advanced Non Small-Cell Lung

35 N Engl J Med 2002; 346: Cancer. 癌症診療指引67 9. Pujol JL, Breton JL, Gervais R, et al. Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-smallcell lung cancer: a phase III study addressing the case for cisplatin. Ann Oncol 2005;16: Tan EH, Szczesna A, Krzakowski M, et al. Randomized study of vinorelbine--gemcitabine versus vinorelbine--carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2005;49: Green MR, Manikhas GM, Orlov S, et al. Abraxane, a novel Cremophor -free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Ann Oncol. 2006;17: Rizvi NA, Riely GJ, Azzoli CG, et al. Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 2008;26: Socinski MA1, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol 2012;30: Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small cell lung cancer previously treated with platinumcontaining chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol 2000;18: Fidias PM, Dakhil SR, Lyss AP, et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2009;27: Zatloukal P, Kanitz E, Magyar P, Jassem J, et al. Gemcitabine in locally advanced and metastatic non-small cell lung cancer: the Central European phase II study. Lung Cancer. 1998;22: Sederholm C, Hillerdal G, Lamberg K, et al. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005;23: Pérol M, Chouaid C, Pérol D, et al. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-smallcell lung cancer. J Clin Oncol. 2012;30: Lilenbaum RC, Herndon JE 2nd, List MA, et al. Single-agent versus combination chemotherapy in advanced non-small-cell

36 20. Ceresoli GL, Gregorc V, Cordio S, et al. Phase II study of weekly paclitaxel as second-line therapy in patients with advanced non-small cell lung cancer. Lung Cancer. 2004;44: Yasuda K, Igishi T, Kawasaki Y, et al. Phase II study of weekly paclitaxel in patients with non-small cell lung cancer who have failed previous treatments. Oncology. 2004;66: cancer: the cancer and leukemia group B (study 9730).J Clin Oncol. 2005;23: lung 癌症診療指引68

37 肺癌放射治療共識 ( ) / 47 Gy (45~49 Gy)/25 1. / 62 Gy (60~64 Gy)/30~32 68 Gy(66~70 Gy) /33~ Gy (50~54 Gy)/25~ ~2.0 Gy ( ) Gy(60-64 Gy)/ Gy (66-70 Gy)/ (a) <2 cm >1 cm 30 Gy (28.5~31.5 Gy)/1 (b) >1 cm 47 Gy (45~49 Gy)/3 58 Gy (55.5~60 Gy)/3 (c) <1 cm 50 Gy (48~52 Gy)4 52 Gy (50~54 Gy)/5 63 Gy (60~66Gy)/5 (d) 63 Gy (60~66 Gy)8 67 Gy (64~70 Gy)/10 (IGRT) 癌症診療指引69

38 肺癌放射治療共識 62 Gy (60~64 Gy)/30~32 68 Gy(66~70 Gy) /33~35 25 Gy (24~26 Gy)/12~13 28 Gy (26~30 Gy) /13~ ~ Gy/10 (extensive stage) 20 Gy/5 1. NCCN clinical practice guidelines in oncology- Non-small cell Lung cancer. Version 2, RTOG 1106 Protocol Information RTOG 1106/ACRIN 6697, Randomized Phase II Trial of Individualized Adaptive Radiotherapy Using During-Treatment FDG-PET/CT and Modern Technology in Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Onishi H, et al. Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in Japanese multi-institutional study. J Thorac Oncol 2007; 2(7 suppl 3): S Stephans KL, et al. A comparison of two stereotactic body radiation fractionation schedules for medically inoperable stage I non-small cell lung cancer: the Cleveland clinic experience. J Thorac Oncol 2009; 4: Jin Jy, rt al. Impact of fraction size on lung radiation toxicity: hypofractionation may be beneficial in dose escalation of radiotherapy for lung cancers. Int J Radiat Oncol boil Phys 2009; Jul 3 6. NCCN clinical practice guidelines in oncology- Small cell Lung cancer. version 1, Paumier, A. et al. Radiotherapy in small-cell lung cancer: where should it go? Lung Cancer, 2010; 69: Sorensen, M. et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2010; 21 Suppl 5: v ICRU Report 83 Prescribing, recording, and reporting photon-beam intensity-modulated radiation therapy (IMRT). J of the ICRU, vol 10(1), 2010 癌症診療指引70

Nivolumab 3 mg/kg 1 Q2W 9 Nivolumab 3 mg/kg 1 Q2W 9 Ipilimumab 1 mg/kg 1 Q2W 參考文獻 1. Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with o

Nivolumab 3 mg/kg 1 Q2W 9 Nivolumab 3 mg/kg 1 Q2W 9 Ipilimumab 1 mg/kg 1 Q2W 參考文獻 1. Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with o 肺癌抗癌藥物治療指引 Small Cell Lung Cancer Chemotherapy as primary or adjuvant therapy Limited Stage (maximum of 4-6 cycles): During chemotherapy + RT, cisplatin/etoposide is recommended The use of myeloid growth