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 factors is not recommended during Cisplatin 60-80 1 Q3W 4-6 1, 2 Etoposide 100 1-3 Q3W 4-6 Carboplatin 5-6 AUC 1 Q3W 4-6 3 Etoposide 100 1-3 Q3W 4-6 Extensive Stage (maximum of 4-6 cycles): Cisplatin 75-80 1 Q3W 4-6 4, 5 Etoposide 100 1-3 Q3W 4-6 Carboplatin 5-6 AUC 1 Q3W 4-6 6 Etoposide 100 1-3 Q3W 4-6 Subsequent Chemotherapy: Clinical trial preferred. Relapse <6 months, PS 0-2: Topotecan 1.5 1-5 Q3W 7 Topotecan 2.3 PO 1-5 Q3W 8 Cyclophosphamide 1000 1 Q3W 7 Doxorubicin 45 1 Q3W Vincristine 2 1 Q3W
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 once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999;340(4):265-271. 2. Saito H, Takada Y, Ichinose Y, et al. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol 2006;24(33): 5247-5252. 3. 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):1231-1238. 4. 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;29:2215-2222. 5. 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 9732. J Clin Oncol 2005;23:3752-3759. 6. Okamoto H, Watanabe K, Nishiwaki Y, et al. Phase II study of area under the plasmaconcentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small cell lung cancer. J Clin Oncol 1999;17(11):3540-3545. 7. 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):658-667. 8. 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;24:5441-5447. 9. 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;17:883-895.
Non-Small Cell Lung Cancer Neoadjuvant and Adjuvant therapy Cisplatin 75-80 1 Q3W 4 1-3 Vinorelbine 25-30 1, 8 Q3W 4 Cisplatin 75-80 1 Q3W 4 19 Vinorelbine 40-60 1, 8 Q3W 4 Cisplatin 60-75 1 Q3W 4 4 Gemcitabine 1250 1, 8 Q3W 4 Cisplatin 60-75 1 Q3W 4 5 Docetaxel 60-75 1 Q3W 4 Cisplatin 60-75 1 Q3W 4 6 Pemetrexed 500 1 Q3W 4 UFUR 200 PO BID/TID 20 Carboplatin 5 AUC 1 Q3W 4 12 Pemetrexed 500 1 Q3W 4 Carboplatin 5 AUC 1 Q3W 4 13 Gemcitabine 1000 1, 8 Q3W 4 Carboplatin 6 AUC 1 Q3W 4 14 Paclitaxel 1000 1 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 Ciaplatin 50 1, 8 Q4W 2 7, 8 Etoposide 50mg PO BID 1, 2, 5, 6 QW 10 Carboplatin 5 AUC 1 Q3W 4 9 Pemetrexed 500 1 Q3W 4 Cisplatin 75 1 Q3W 3 10 Pemetrexed 500 1 Q3W 3 + 4 (additional) Paclitaxel 45-50 1 QW 11 Carboplatin 2 AUC 1 QW ± Paclitaxel 200 1 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 Erotinib 150 mg QD AC 15 Afatinib 40 mg QD AC 16 Gefitinib 250 mg QD 17 ALK positive Crizotinib 250 mg BID 18
參考文獻 1. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-lung cancer. N Engl J Med 2005;352:2589-2597. 2. 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;350:351-360. 3. 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;7:719-727. 4. 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-small-cell lung cancer. J Clin Oncol 2012;30:3516-3524. 5. 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;21:3016-3024. 6. 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;24:986-992. 7. Albain KS, Crowley JJ, Turrisi AT III, et al. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: A Southwest Oncology Group Phase II Study, SWOG 9019. J Clin Oncol 2002;20:3454-3460. 8. 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 9410. J Natl Cancer Inst. 2011;103:1452-1460. 9. 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 Clin Oncol 2011;29:3120-3125. 10. 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;87:232-240. 11. 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;16:187-199. 12. Zhang L, Ou W, Liu Q, et al. Pemetrexed plus carboplatin as adjuvant chemotherapy in patients
with curative resected non-squamous non-small cell lung cancer. Thoracic Cancer. 2014;5(1):50-56. 13. 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):583-7. 14. Strauss GM, Herndon JE, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-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):5043-51. 15. Product Information: TARCEVA(R) oral tablets, erlotinib oral tablets. OSI Pharmaceuticals, LLC (per FDA), Farmingdale, NY, 2013. 16. Product Information: GILOTRIF(TM) oral tablets, afatinib oral tablets. Boehringer Ingelheim Pharmaceuticals, Inc. (per FDA), Ridgefield, CT, 2013. 17. Product Information: IRESSA(R) oral tablets, gefitinib oral tablets. AstraZeneca Pharmaceuticals (per FDA), Wilmington, DE, 2015. 18. Product Information: XALKORI(R) oral capsules, crizotinib oral capsules. Pfizer Labs (per FDA), New York, NY, 2013. 19. NCCN, [NSCL-D]. Non-small cell lung cancer, version 9, 2017. 20. Product Information: UFUR Capsule. tegafur, uracil oral capsules. 2015.
Systemic Therapy for Advanced or Metastatic Disease of NSCLC First-line systemic therapy options Adenocarcinoma, large cell, NSCLC NOS (PS 0-1) Bevacizumab 15 mg/kg 1 Q3W 6 1 Carboplatin 6 AUC 1 Q3W Paclitaxel 200 1 Q3W 藥品名劑量 mg/m 2 給藥日頻率週期參考文獻 Bevacizumab 15 mg/kg 1 Q3W 4 2 Carboplatin 6 AUC 1 Q3W Pemetrexed 500 1 Q3W Bevacizumab 15 mg/kg 1 Q3W 4 3 Cisplatin 75 1 Q3W Pemetrexed 500 1 Q3W Carboplatin 6 AUC 1 Q3W 6 4 Albumin-Paclitaxel 100 1, 8, 15 Q3W Carboplatin 6 AUC Q3W 5 Docetaxel 75 Q3W Carboplatin 4-5 AUC 1 Q4W 7 Etoposide 50mg PO BID 1-14 or 1-21 Q4W Carboplatin 5 AUC 1 Q4W 4 8 Gemcitabine 1000 1, 8, 15 Q4W 4 Carboplatin 6 AUC 1 Q3W 9 Paclitaxel 200 1 Q3W Carboplatin 6 AUC 1 Q3W 6 10 Pemetrexed 500 1 Q3W 6 Cisplatin 75 1 Q3W 5 Docetaxel 75 1 Q3W
Cisplatin 100 1 Q3W 11 Etoposide 100 1-3 Q3W Cisplatin 80 1 Q3W 9 Gemcitabine 1000 1, 8 Q3W Cisplatin 75 1 Q3W 6 12 Gemcitabine 1250 1, 8 Q3W 6 Paclitaxel 135 1 Q3W 13 Cisplatin 75 2 Q3W Cisplatin 75 1 Q3W 12 Pemetrexed 500 1 Q3W Gemcitabine 1000 1, 8 Q3W 8 14 Docetaxel 85 8 Q3W 8 Gemcitabine 1000 1, 8 Q3W 6 15 Vinorelbine 25 1, 8 Q3W 6 Pembrolizumab 2 mg/kg 1 Q3W 4 28 Carboplatin 5 AUC 1 Q3W 4 Pemetrexed 500 1 Q3W 4 Adenocarcinoma, large cell, NSCLC NOS (PS 2) Albumin-Paclitaxel 260 1 Q3W 16 Albumin-Paclitaxel 100 1, 8, 15 Q4W 17 Carboplatin 6 AUC 1 Q3W 6 18 Albumin-Paclitaxel 100 1, 8, 15 Q3W 6
Carboplatin 6 AUC 1 Q3W 5 Docetaxel 75 1 Q3W Carboplatin 325 1 6 Etoposide 100 1-3 Carboplatin 4-5 AUC 1 Q4W 7 Etoposide 50 1-14 or 1-21 Q4W Carboplatin 5 AUC 1 Q4W 4 8 Gemcitabine 1000 1, 8, 15 Q4W Carboplatin 6 AUC 1 Q3W 9 Paclitaxel 200 1 Q3W Carboplatin 6 AUC 1 Q3W 6 10 Pemetrexed 500 1 Q3W Docetaxel 75 1 Q3W 6 19, 20 Gemcitabine 1250 1, 8, 15 Q4W 9 21 Gemcitabine 1250 1, 8 Q3W 6 22, 23 Gemcitabine 1000 1, 8 Q3W 8 14 Docetaxel 85 8 Q3W 8 Gemcitabine 1000 1, 8 Q3W 6 15 Vinorelbine 25 1, 8 Q3W 6 Paclitaxel 225 1 Q3W 6 24 Paclitaxel 80 1, 8, 15 Q4W 4 25, 26
Pemetrexed 500 1 Q3W 27 參考文獻 1. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small lung cancer. N Engl J Med 2006;355:2542-2550. 2. 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;31:3004-3011. 3. 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;31:3004-3011. 4. 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;30:2055-2062. 5. 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):3016-3024. 6. 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 07861. J Clin Oncol 1990;8:1556-1562. 7. 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;34:1710-1714. 8. 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;98:542-553. 9. 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 nonsmall-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol 2007;18:317-323. 10. 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;11:690-696.
11. 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;17:12-18. 12. 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;26:3543-3551. 13. 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; 346:92-98. 14. Pujol JL, Breton JL, Gervais R, et al. Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin. Ann Oncol 2005;16:602-610. 15. 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;49:233-240. 16. 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;17:1263-1268. 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;26:639-643. 18. 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;30:2055-2062. 19. 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;18:2354-2362. 20. 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;27:591-598. 21. 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;22:243-250. 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;23:8380-8388. 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-small-cell lung cancer. J Clin Oncol. 2012;30:3516-24. 24. 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;23:190-196. 25. 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;44:231-239. 26. 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;66:347-352. 27. Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22:1589-1597. 28. 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;17:1497-1508.
Squamous cell carcinoma (PS 0-1) Carboplatin 6 AUC 1 Q3W 13 Albumin-Paclitaxel 100 1, 8, 15 Q3W Carboplatin 6 AUC 1 Q3W 1 Docetaxel 75 1 Q3W Carboplatin 5 AUC 1 Q4W 4 Gemcitabine 1000 1, 8, 15 Q4W Paclitaxel 200 1 Q3W 5 Carboplatin 6 AUC 1 Q3W Docetaxel 75 1 Q3W 1 Cisplatin 75 1 Q3W Cisplatin 100 1 Q3W 6 Etoposide 100 1-3 Q3W Cisplatin 80 1 Q3W 5 Gemcitabine 1000 1, 8 Q3W Cisplatin 75 1 Q3W 7 Gemcitabine 1250 1, 8 Q3W Paclitaxel 135 1 Q3W 8 Cisplatin 75 2 Q3W Gemcitabine 1000 1, 8 Q3W 9 Docetaxel 85 8 Q3W Gemcitabine 1000 1, 8 Q3W 10 Vinorelbine 25 1, 8 Q3W
Squamous cell carcinoma (PS 2) Albumin-Paclitaxel 260 1 Q3W 11 Carboplatin 6 AUC 1 Q3W 12, 13 Albumin-Paclitaxel 100 1, 8, 15 Q3W Carboplatin 6 AUC 1 Q3W 1 Docetaxel 75 1 Q3W Carboplatin 325 1 2 Etoposide 100 1-3 Carboplatin 4-5 AUC 1 Q4W 3 Etoposide 50 1-14 or 1-21 Q4W Carboplatin 5 AUC 1 Q4W 4 Gemcitabine 1000 1, 8, 15 Q4W Carboplatin 6 AUC 1 Q3W 5 Paclitaxel 200 1 Q3W Docetaxel 75 1 Q3W 14, 15 Gemcitabine 1250 1, 8, 15 Q4W 16 Gemcitabine 1250 1, 8 Q3W 17, 18 Gemcitabine 1000 1, 8 Q3W 9 Docetaxel 85 8 Q3W Gemcitabine 1000 1, 8 Q3W 10 Vinorelbine 25 1, 8 Q3W Paclitaxel 225 1 Q3W 19
Paclitaxel 80 1, 8, 15 Q4W 20, 21 參考文獻 1. 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):3016-3024. 2. 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 07861. J Clin Oncol 1990;8:1556-1562. 3. 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;34:1710-1714. 4. 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;98:542-553. 5. 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;18:317-323. 6. 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;17:12-18. 7. 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;26:3543-3551. 8. 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; 346:92-98. 9. Pujol JL, Breton JL, Gervais R, et al. Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin. Ann Oncol 2005;16:602-610. 10. 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;49:233-240. 11. 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;17:1263-1268.
12. 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;26:639-643. 13. 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;30:2055-2062. 14. 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;18:2354-2362. 15. 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;27:591-598. 16. 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;22:243-250. 17. 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;23:8380-8388. 18. 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-small-cell lung cancer. J Clin Oncol. 2012;30:3516-24. 19. 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;23:190-196. 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;44:231-239. 21. 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;66:347-352.