臨床婦人科産科61巻10号

2007年10月発行

今月の臨床 ここまできた分子標的治療

分子標的治療の臨床応用

6．肺癌

著者： 秋田弘俊¹

所属機関： ¹北海道大学大学院医学研究科腫瘍内科学分野

ページ範囲：P.1282 - P.1287

文献概要

はじめに
　上皮成長因子（EGF）受容体阻害薬，血管新生阻害薬，マルチターゲット・チロシンキナーゼ阻害薬をはじめとする分子標的薬の臨床開発によって，肺癌，特に非小細胞肺癌の薬物療法に新しい時代が到来している．新規分子標的薬の臨床開発とともに，分子標的薬を初回治療およびセカンドライン以降の治療の治療戦略にどのように組み込むか，特定の分子標的薬を投与すべき患者群を同定し適切な患者のもとに適切な薬剤をいかにして届けるか，といった研究が進行している．

参考文献

1）Fukuoka M, Yano S, Giaccone G, et al : Multi─institutional randomized phase II trial of gefitinib for previously treated patients with advanced non─small─cell lung cancer（The IDEAL 1 Trial）．J Clin oncol 21 : 2237─2246, 2003

2）Kris MG, Natale RB, Herbst RS, et al : Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non─small cell lung cancer : a randomized trial. JAMA 290 : 2149─2158, 2003

3）Thatcher N, Chang A, Parikh P, et al : Gefitinib plus best supportive care in previously treated patients with refractory advanced non─small─cell lung cancer : results from a randomised, placebo─controlled, multicentre study（Iressa Survival Evaluation in Lung Cancer）．Lancet 366 : 1527─1537, 2005

4）Shepherd FA, Rodrigues PJ, Ciuleanu T, et al : Erlotinib in previously treated non─small─cell lung cancer. N Engl J Med 353 : 123─132, 2005

5）Giaccone G, Herbst RS, Manegold C, et al : Gefitinib in combination with gemcitabine and cisplatin in advanced non─small─cell lung cancer : a phase III trial─INTACT 1. J Clin Oncol 22 : 777─784, 2004

6）Herbst RS, Giaccone G, Schiller JH, et al : Gefitinib in combination with paclitaxel and carboplatin in advanced non─small─cell lung cancer : a phase III trial──INTACT 2. J Clin Oncol 22 : 785─794, 2004

7）Gatzemeier U, Pluzanska A, Szczesna A, et al : Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non─small─cell lung cancer : the Tarceva Lung Cancer Investigation Trial. J Clin Oncol 25 : 1545─1552, 2007

8）Herbst RS, Prager D, Hermann R, et al : TRIBUTE : A phase III trial of erlotinib hydrochloride（OSI─774）combined with carboplatin and paclitaxel chemotherapy in advanced non─small─cell lung cancer. J Clin Oncol 23 : 5892─5899, 2005

9）Lynch TJ, Bell DW, Sordella R, et al : Activating mutations in the epidermal growth factor receptor underlying responsiveness of non─small─cell lung cancer to gefitinib. N Engl J Med 350 : 2129─2139, 2004

10）Paez JG, Janne PA, Lee JC, et al : EGFR mutations in lung cancer : correlation with clinical response to gefitinib therapy. Science 304 : 1479─1500, 2004

11）Sharma SV, Bell DW, Settleman J, et al : Epidermal growth factor receptor mutations in lung cancer. Nature Rev Cancer 7 : 169─181, 2007

12）Weinberg RA : The Biology of Cancer. p769, Garland Science, New York, 2007

13）Inoue A, Suzuki T, Fukuhara T, et al : Prospective phase II study of gefitinib for chemotherapy─naive patients with advanced non─small─cell lung cancer with epidermal growth factor receptor gene mutations. J Clin Oncol 24 : 3340─3346, 2006

14）Asahina H, Yamazaki K, kinoshita I, et al : A phase II trial of gefitinib as first─line therapy for advanced non─small cell lung cancer with epidermal growth factor receptor mutations. Br J Cancer 96 : 998─1004, 2006

15）Sutani A, Nagai Y, Udagawa K, et al : Gefitinib for non─small─cell lung cancer patients with epidermal growth factor receptor gene mutations screened by peptide nucleic acid─locked nucleic acid PCR clamp. Br J Cancer 95 : 1483─1489, 2006

16）Johonson DH, Fehrenbacher L, Novotny WF, et al : Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non─small─cell lung cancer. J Clin Oncol 22 : 2184─2191, 2004

17）Sandler A, Gray R, Perry MC, et al : Paclitaxel─carboplatin alone or with bevacizumab for non─small─cell lung cancer. N Engl J Med 355 : 2542─2550, 2006

18）Manegoldc, von Pawel J, Zatloukal P, et al : Randomised, double─blind multicentre phase III study of bevacizumab in combination with cisplatin and gemcitabine in chemotherapy─na?ve patients with advanced or recurrent non─squamous non-small cell lung cancer（NSCLC）: BO17704. Proc Am Soc Clin Oncol Abs# LBA7514, 2007

19）Herbst RS, Johnson DH, Mininberg E, et al : Phase I/II trial evaluating the anti─vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER─1／epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non─small─cell lung cancer. J Clin Oncol 23 : 2544─2555, 2005

20）Heymach J, Johnson BE, Prager D, et al : A phase IItrial of ZD6474 plus docetaxel in patients with previously treated NSCLC : follow─up results. Proc Am Soc Clin Oncol Abs＃7016, 2006

21）Socinski MA, Novello S, Sanchez JM, et al : Efficacy and safety of sunitinib in previously treated, advanced non─small cell lung cancer（NSCLC）: preliminary results od a multicenter phase II trial. Proc Am Soc Clin Oncol Abs＃7001, 2006

22）Gatzemeier U, Blumenschein G, Fosella F, et al : Phase II trial of single─agent sorafenib in patients with advanced non─small cell lung carcinoma. Proc Am Soc Clin Oncol Abs＃7002, 2006