• 浙江省腫瘤醫(yī)院綜合治療科（浙江杭州 310004）;

肺癌是全球的一大健康難題，每年新發(fā)病人數(shù)為140萬，是最常見的惡性腫瘤之一。我國的肺癌患病絕對人數(shù)為全世界第1位。美國癌癥研究會(huì)的數(shù)據(jù)顯示無論在男性還是女性中，肺癌都是病死率最高的惡性腫瘤，幾乎占所有癌癥死亡原因的1/3[1]。該研究會(huì)的調(diào)查資料顯示，在1990~2000年間盡管男性肺癌病死率平均每年下降1.6%[2]，但男性肺癌病死率仍然超過前列腺癌與直腸癌[3]。1950~2000年間，女性肺癌發(fā)病率有了驚人的上升[2]，現(xiàn)在女性肺癌病死人數(shù)已超過了乳腺癌、宮頸癌與卵巢癌死亡人數(shù)的總和[3]。目前總的肺癌病死率仍居高不下，在美國1989~1994年肺癌的5年生存率為15%，80%~85%的肺癌是非小細(xì)胞肺癌（NSCLC）[4]；70%~80%的NSCLC確診時(shí)已經(jīng)為中晚期，能進(jìn)行手術(shù)治療的病例不超過40%，進(jìn)展期的NSCLC的5年生存率為8%~10%[5]。

引用本文： 方美玉. 進(jìn)展期非小細(xì)胞肺癌藥物治療進(jìn)展. 中國呼吸與危重監(jiān)護(hù)雜志, 2008, 08(6): 481-484. doi: 復(fù)制

1. 33 Pirker RA，Szczesna J，von Pawel，et al.A randomized，multicenter，phase III study of cetuximab in combination with cisplatin/vinorelbine（CV） versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer（NSCLC）.J Clin Oncol，2008，26（suppl）：3. 34 Kim ES，Mauer AM，Tran HT，et al.A phase II study of cetuximab，an epidermal growth factor receptor（EGFr） blocking antibody，in combination with docetaxel in chemotherapy refractory/resistant patients with advanced non-small cell lung cancer：final report（Abstract）.Proc Am Soc Clin Oncol，2003，22：642.
2. American Cancer Society.Cancer Facts & Figures 2004.Atlanta，GA：American Cancer Society，2004，22-23.
3. Greenlee RT，Murray T，Bolden S，et al.Cancer statistics，2000.CA Cancer J Clin，2000，50：7-33.
4. Jemal A，Murray T，Samuels A，et al.Cancer statistics，2003.CA Cancer J Clin，2003，53：5-26.
5. Landis SH，Murray T，Bolden S，et al.Cancer statistics，1999.CA Cancer J Clin，1999，49：8-31.
6. Mountain CF.International staging system for lung cancer.In：Pass H，Mitchell J，Johnson D，Turrisi A，Minna J，eds.Lung cancer second.Philadelphia：Lippincott Wiliams Wilkin，2000，591-601.
7. Chemotherapy in non-small cell lung cancer：a meta-analysis using updated data on individual patients from 52 randomised clinical trials.Non-small Cell Lung Cancer Collaborative Group.BMJ，1995，311：899-909.
8. Gandara DR，Crowley J，Livingston RB，et al.Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer：a phase III study of the Southwest Oncology Group.J Clin Oncol，1993，11：873-878.
9. Hotta K，Matsuo K，Ueoka H，et al.Meta-analysis of randomized clinical trials comparing Cisplatin to Carboplatin in patients with advanced non-small-cell lung cancer.J Clin Oncol，2004，22：3852-3859.
10. Ardizzoni A，Boni L，Tiseo M，et al.Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer：an individual patient data meta-analysis.J Natl Cancer Inst，2007，99：847-857.
11. Monnet I，Brienza S，Hugret F，et al.Phase II study of oxaliplatin in poor-prognosis non-small cell lung cancer（NSCLC）.ATTIT.Association pour le Traitement des Tumeurs Intra Thoraciques.Eur J Cancer，1998，34：1124-1127.
12. Faivre S，Raymond E，Woynarowski JM，et al.Supraadditive effect of 2’，2’-difluorodeoxycytidine（gemcitabine） in combination with oxaliplatin in human cancer cell lines.Cancer Chemother Parmacol，1999，44：117-123.
13. Takigawa N，Segawa Y，Ueoka H，et al.Combination of nedaplatin and vindesine for treatment of relapsed or refractory non-small-cell lung cancer.Cancer Chemother Pharmacol，2000，46：272-278.
14. Oshita F，Yamada K，Kato Y，et al.Phase I/II study of escalating doses of nedaplatin in combination with irinotecan for advanced non-small-cell lung cancer.Chemother Pharmacol，2003，52：73-78.
15. Saris CP，van de Vaart PJ，Rietbroek RC，et al.In vitro formation of DNA adducts by cisplatin，lobaplatin and oxaliplatin in calf thymus DNA in solution and in cultured human cells.Carcinogenesis，1996，17：2763-2769.
16. 楊柳青，施毅，秦叔逵，等.洛鉑聯(lián)合長春瑞濱治療晚期非小細(xì)胞肺癌的臨床研究.臨床腫瘤學(xué)雜志，2006，11：890-894.
17. 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.
18. Stathopoulos GP，Veslemes M，Georgatou N，et al.Front-line paclitaxel-vinorelbine versus paclitaxel-carboplatin in patients with advanced non-small-cell lung cancer：a randomized phase III trial.Ann Oncol，2004，15：1048-1055.
19. Gatzemeier U，Shepherd FA，Le Chevalier T，et al.Activity of gemcitabine in patients with non-small cell lung cancer：a multicentre，extended phase II study.Eur J Cancer，1996，32A：243-248.
20. Ricci S，Antonuzzo A，Galli L，et al.Gemcitabine monotherapy in elderly patients with advanced non-small cell lung cancer：a multicenter phase II study.Lung Cancer，2000，27：75-80.
21. Smit EF，van Meerbeeck JP，Lianes P，et al.Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer：a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975.J Clin Oncol，2003，21：3909-3917.
22. 孫燕，主編.內(nèi)科腫瘤學(xué).北京：人民衛(wèi)生出版社，2001，427.
23. Georgoulias V，Ardavanis A，Tsiafaki X，et al.Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer：a phase III randomized trial.J Clin Oncol，2005，23：2937-2945.
24. Negoro S，Masuda N，Takada Y，et al.Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer.Br J Cancer，2003，88：335-341.
25. Georgoulias V，Ardavanis A，Agelidou A，et al.Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer：a randomized，multicenter phase III trial.J Clin Oncol，2004，22：2602-2609.
26. Weiss GJ，Langer C，Rosell R，et al.Elderly patients benefit from second-line cytotoxic chemotherapy：a subset analysis of a randomized phase III trial of pemetrexed compared with docetaxel in patients with previously treated advanced non-small-cell lung cancer.J Clin Oncol，2006，24：4405-4411.
27. 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.
28. 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.
29. Smit EF，van Meerbeeck JP，Lianes P，et al.Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer：a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975.J Clin Oncol，2003，21：3909-3917.
30. Alberola V，Camps C，Provencio M，et al.Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer：a Spanish Lung Cancer Group phase III randomized trial.J Clin Oncol，2003，21：3207-3213.
31. Olaussen KA，Dunant A，F(xiàn)ouret P，et al.DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy.N Engl J Med，2006，355：983-991.
32. Janessa J Laskin .Adjuvant chemotherapy for non-small cell lung cancer：the new standard of care.Future Oncology，2005，1：619-623.
33. Bell DW，Lynch TJ，Haserlat SM，et al.Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer：molecular analysis of the IDEAL/INTACT gefitinib trials.J Clin Oncol，2005，23：8081-8092.
34. Belani CP，Wang W，Johnson DH，et al.Induction chemotherapy followed by standard thoracic radiotherapy（Std.TRT） vs.hyperfractionated accelerated radiotherapy（HART） for patients with unresectable stage Ⅲ A & B non-small cell lung cancer（NSCLC）：phase Ⅲ study of the Eastern Cooperative Oncology Group（ECOG 2597）.Proc Am Soc Clin Oncol，2003，21：2264-2271.
35. Sandler A，Gray R，Perry MC，et al.Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.N Engl J Med，2006，355：2542-2550.
36. Fanucchi MP，F(xiàn)ossella FV，Belt R，et al.Randomized phase II study of bortezomib alone and bortezomib in combination with docetaxel in previously treated advanced non-small-cell lung cancer.J Clin Oncol，2006，24：5025-5033.
37. Liu B，Barrett T，Choyke P，et al.A phase II study of BAY 43-9006（sorafenib） in patients with relapsed non-small cell lung cancer（NSCLC）.J Clin Oncol，2006，24（18 Suppl）：17119.
38. Chen S，Yu L，Jiang C，et al.Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer.J Clin Oncol，2005，23：1538-1547.
  1. 1. 33 Pirker RA，Szczesna J，von Pawel，et al.A randomized，multicenter，phase III study of cetuximab in combination with cisplatin/vinorelbine（CV） versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer（NSCLC）.J Clin Oncol，2008，26（suppl）：3. 34 Kim ES，Mauer AM，Tran HT，et al.A phase II study of cetuximab，an epidermal growth factor receptor（EGFr） blocking antibody，in combination with docetaxel in chemotherapy refractory/resistant patients with advanced non-small cell lung cancer：final report（Abstract）.Proc Am Soc Clin Oncol，2003，22：642.
  2. 2. American Cancer Society.Cancer Facts & Figures 2004.Atlanta，GA：American Cancer Society，2004，22-23.
  3. 3. Greenlee RT，Murray T，Bolden S，et al.Cancer statistics，2000.CA Cancer J Clin，2000，50：7-33.
  4. 4. Jemal A，Murray T，Samuels A，et al.Cancer statistics，2003.CA Cancer J Clin，2003，53：5-26.
  5. 5. Landis SH，Murray T，Bolden S，et al.Cancer statistics，1999.CA Cancer J Clin，1999，49：8-31.
  6. 6. Mountain CF.International staging system for lung cancer.In：Pass H，Mitchell J，Johnson D，Turrisi A，Minna J，eds.Lung cancer second.Philadelphia：Lippincott Wiliams Wilkin，2000，591-601.
  7. 7. Chemotherapy in non-small cell lung cancer：a meta-analysis using updated data on individual patients from 52 randomised clinical trials.Non-small Cell Lung Cancer Collaborative Group.BMJ，1995，311：899-909.
  8. 8. Gandara DR，Crowley J，Livingston RB，et al.Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer：a phase III study of the Southwest Oncology Group.J Clin Oncol，1993，11：873-878.
  9. 9. Hotta K，Matsuo K，Ueoka H，et al.Meta-analysis of randomized clinical trials comparing Cisplatin to Carboplatin in patients with advanced non-small-cell lung cancer.J Clin Oncol，2004，22：3852-3859.
  10. 10. Ardizzoni A，Boni L，Tiseo M，et al.Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer：an individual patient data meta-analysis.J Natl Cancer Inst，2007，99：847-857.
  11. 11. Monnet I，Brienza S，Hugret F，et al.Phase II study of oxaliplatin in poor-prognosis non-small cell lung cancer（NSCLC）.ATTIT.Association pour le Traitement des Tumeurs Intra Thoraciques.Eur J Cancer，1998，34：1124-1127.
  12. 12. Faivre S，Raymond E，Woynarowski JM，et al.Supraadditive effect of 2’，2’-difluorodeoxycytidine（gemcitabine） in combination with oxaliplatin in human cancer cell lines.Cancer Chemother Parmacol，1999，44：117-123.
  13. 13. Takigawa N，Segawa Y，Ueoka H，et al.Combination of nedaplatin and vindesine for treatment of relapsed or refractory non-small-cell lung cancer.Cancer Chemother Pharmacol，2000，46：272-278.
  14. 14. Oshita F，Yamada K，Kato Y，et al.Phase I/II study of escalating doses of nedaplatin in combination with irinotecan for advanced non-small-cell lung cancer.Chemother Pharmacol，2003，52：73-78.
  15. 15. Saris CP，van de Vaart PJ，Rietbroek RC，et al.In vitro formation of DNA adducts by cisplatin，lobaplatin and oxaliplatin in calf thymus DNA in solution and in cultured human cells.Carcinogenesis，1996，17：2763-2769.
  16. 16. 楊柳青，施毅，秦叔逵，等.洛鉑聯(lián)合長春瑞濱治療晚期非小細(xì)胞肺癌的臨床研究.臨床腫瘤學(xué)雜志，2006，11：890-894.
  17. 17. 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.
  18. 18. Stathopoulos GP，Veslemes M，Georgatou N，et al.Front-line paclitaxel-vinorelbine versus paclitaxel-carboplatin in patients with advanced non-small-cell lung cancer：a randomized phase III trial.Ann Oncol，2004，15：1048-1055.
  19. 19. Gatzemeier U，Shepherd FA，Le Chevalier T，et al.Activity of gemcitabine in patients with non-small cell lung cancer：a multicentre，extended phase II study.Eur J Cancer，1996，32A：243-248.
  20. 20. Ricci S，Antonuzzo A，Galli L，et al.Gemcitabine monotherapy in elderly patients with advanced non-small cell lung cancer：a multicenter phase II study.Lung Cancer，2000，27：75-80.
  21. 21. Smit EF，van Meerbeeck JP，Lianes P，et al.Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer：a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975.J Clin Oncol，2003，21：3909-3917.
  22. 22. 孫燕，主編.內(nèi)科腫瘤學(xué).北京：人民衛(wèi)生出版社，2001，427.
  23. 23. Georgoulias V，Ardavanis A，Tsiafaki X，et al.Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer：a phase III randomized trial.J Clin Oncol，2005，23：2937-2945.
  24. 24. Negoro S，Masuda N，Takada Y，et al.Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer.Br J Cancer，2003，88：335-341.
  25. 25. Georgoulias V，Ardavanis A，Agelidou A，et al.Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer：a randomized，multicenter phase III trial.J Clin Oncol，2004，22：2602-2609.
  26. 26. Weiss GJ，Langer C，Rosell R，et al.Elderly patients benefit from second-line cytotoxic chemotherapy：a subset analysis of a randomized phase III trial of pemetrexed compared with docetaxel in patients with previously treated advanced non-small-cell lung cancer.J Clin Oncol，2006，24：4405-4411.
  27. 27. 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.
  28. 28. 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.
  29. 29. Smit EF，van Meerbeeck JP，Lianes P，et al.Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer：a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975.J Clin Oncol，2003，21：3909-3917.
  30. 30. Alberola V，Camps C，Provencio M，et al.Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer：a Spanish Lung Cancer Group phase III randomized trial.J Clin Oncol，2003，21：3207-3213.
  31. 31. Olaussen KA，Dunant A，F(xiàn)ouret P，et al.DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy.N Engl J Med，2006，355：983-991.
  32. 32. Janessa J Laskin .Adjuvant chemotherapy for non-small cell lung cancer：the new standard of care.Future Oncology，2005，1：619-623.
  33. 33. Bell DW，Lynch TJ，Haserlat SM，et al.Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer：molecular analysis of the IDEAL/INTACT gefitinib trials.J Clin Oncol，2005，23：8081-8092.
  34. 34. Belani CP，Wang W，Johnson DH，et al.Induction chemotherapy followed by standard thoracic radiotherapy（Std.TRT） vs.hyperfractionated accelerated radiotherapy（HART） for patients with unresectable stage Ⅲ A & B non-small cell lung cancer（NSCLC）：phase Ⅲ study of the Eastern Cooperative Oncology Group（ECOG 2597）.Proc Am Soc Clin Oncol，2003，21：2264-2271.
  35. 35. Sandler A，Gray R，Perry MC，et al.Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.N Engl J Med，2006，355：2542-2550.
  36. 36. Fanucchi MP，F(xiàn)ossella FV，Belt R，et al.Randomized phase II study of bortezomib alone and bortezomib in combination with docetaxel in previously treated advanced non-small-cell lung cancer.J Clin Oncol，2006，24：5025-5033.
  37. 37. Liu B，Barrett T，Choyke P，et al.A phase II study of BAY 43-9006（sorafenib） in patients with relapsed non-small cell lung cancer（NSCLC）.J Clin Oncol，2006，24（18 Suppl）：17119.
  38. 38. Chen S，Yu L，Jiang C，et al.Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer.J Clin Oncol，2005，23：1538-1547.