进展期非小细胞肺癌药物治疗进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

方美玉

FANG Mei-yu;

Corresponding author：

Keywords：

非小细胞肺癌; 药物治疗

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肺癌是全球的一大健康难题，每年新发病人数为140万，是最常见的恶性肿瘤之一。我国的肺癌患病绝对人数为全世界第1位。美国癌症研究会的数据显示无论在男性还是女性中，肺癌都是病死率最高的恶性肿瘤，几乎占所有癌症死亡原因的1/3[1]。该研究会的调查资料显示，在1990~2000年间尽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过前列腺癌与直肠癌[3]。1950~2000年间，女性肺癌发病率有了惊人的上升[2]，现在女性肺癌病死人数已超过了乳腺癌、宫颈癌与卵巢癌死亡人数的总和[3]。目前总的肺癌病死率仍居高不下，在美国1989~1994年肺癌的5年生存率为15%，80%~85%的肺癌是非小细胞肺癌（NSCLC）[4]；70%~80%的NSCLC确诊时已经为中晚期，能进行手术治疗的病例不超过40%，进展期的NSCLC的5年生存率为8%~10%[5]。

Citation： 方美玉. 进展期非小细胞肺癌药物治疗进展. Chinese Journal of Respiratory and Critical Care Medicine, 2008, 08(6): 481-484. doi: Copy

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.	杨柳青，施毅，秦叔逵，等.洛铂联合长春瑞滨治疗晚期非小细胞肺癌的临床研究.临床肿瘤学杂志，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.	孙燕，主编.内科肿瘤学.北京：人民卫生出版社，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，Fouret 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，Fossella 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. 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. 杨柳青，施毅，秦叔逵，等.洛铂联合长春瑞滨治疗晚期非小细胞肺癌的临床研究.临床肿瘤学杂志，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. 孙燕，主编.内科肿瘤学.北京：人民卫生出版社，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，Fouret 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，Fossella 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.

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进展期非小细胞肺癌药物治疗进展

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