Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
권호 표지

Drugs for Lung Cancer Treatment

폐암에 대한 치료 약물들

  • Kim, Young-Chul (Division of Pulmonology, Internal Medicine, Chonnam National University Medical School, Hwasun Hospital) ;
  • Kim, Kyu-Sik (Division of Pulmonology, Internal Medicine, Chonnam National University Medical School, Hwasun Hospital)
  • 김영철 (전남 대학교 의과대학 내과학교실) ;
  • 김규식 (전남 대학교 의과대학 내과학교실)
  • Published : 2006.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Keywords

References

  1. Seo JH, Jeong CS. Death rate statistics of Korea, 2003. Korea National Statistical Office; 2004
  2. Reck M, Gatzemeier U. Chemotherapy in stage-IV NSCLC. Lung Cancer 2004;45(Suppl 2):S217-22 https://doi.org/10.1016/j.lungcan.2004.07.972
  3. Fong KM, Sekido Y, Minna JD. Molecular pathogenesis of lung cancer. J Thorac Cardiovasc Surg 1999;118:1136-52 https://doi.org/10.1016/S0022-5223(99)70121-2
  4. Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker S Jr, et al. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol 2004;22:330-53 https://doi.org/10.1200/JCO.2004.09.053
  5. Einhorn LH. Carboplatin versus cisplatin in lung cancer. Lung Cancer 2005;49(Suppl 3):S32-5
  6. Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M. Meta-analysis of randomized clinical trials comparing cisplatin to carboplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol 2004;22:3852-9 https://doi.org/10.1200/JCO.2004.02.109
  7. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92-8 https://doi.org/10.1056/NEJMoa011954
  8. Le Chevalier T, Scagliotti G, Natale R, Danson S, Rosell R, Stahel R, et al. Efficacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in advanced non-small-cell lung cancer: a meta-analysis of survival outcomes. Lung Cancer 2005;47:69-80 https://doi.org/10.1016/j.lungcan.2004.10.014
  9. KASLC. Web based clinical trial manager 2005. Available from: URL: http://lung.healthroad.co.kr/
  10. Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, 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(9):1589-97 https://doi.org/10.1200/JCO.2004.08.163
  11. NCI. Small Cell Lung Cancer (PDQ$\Re$): Treatment 2006. Available from: URL: http://www.cancer. gov/cancertopics/pdq/treatment/small-cell-lung/healt hprofessional
  12. Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 2002; 346:85-91 https://doi.org/10.1056/NEJMoa003034
  13. Salgia R, Skarin AT. Novel therapies for advanced non-small cell lung cancer-1. UpToDate CD-ROM 2004 Last; 12.3
  14. Salgia R, Skarin AT. Novel therapies for advanced non-small cell lung cancer-2. UpToDate CD-ROM 2004 Last; 12.3
  15. Dy GK, Adjei AA. Novel targets for lung cancer therapy: part I. J Clin Oncol 2002;20:2881-94 https://doi.org/10.1200/JCO.2002.11.145
  16. Arteaga CL, Khuri F, Krystal G, Sebti S. Overview of rationale and clinical trials with signal transduction inhibitors in lung cancer. Semin Oncol 2002;29(1 Suppl 4):15-26 https://doi.org/10.1053/sonc.2002.37263
  17. Herbst RS, LoRusso PM, Purdom M, Ward D. Dermatologic side effects associated with gefitinib therapy: clinical experience and management. Clin Lung Cancer 2003;4:366-9 https://doi.org/10.3816/CLC.2003.n.016
  18. Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, 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 2003;290:2149-58 https://doi.org/10.1001/jama.290.16.2149
  19. Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, 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 2003;2-1:2237-46
  20. Miller VA, Kris MG, Shah N, PatelJ, Azzoli C, Gomez J, et al. Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol 2004;22:1103-9 https://doi.org/10.1200/JCO.2004.08.158
  21. Park J, Park BB, Kim JY, Lee SH, Lee SI, Kim HY, et al. Gefitinib (ZD1839) monotherapy as a salvage regimen for previously treated advanced non-small cell lung cancer. Clin Cancer Res 2004;10:4383-8 https://doi.org/10.1158/1078-0432.CCR-04-0189
  22. Huang SF, Liu HP, Li LH, Ku YC, Fu YN, Tsai HY, et al. High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res 2004;10:8195-203 https://doi.org/10.1158/1078-0432.CCR-04-1245
  23. Kim KS, Jeong JY, Kim YC, Na KJ, Kim YH, Ahn SJ, et al. Predictors of the response to gefitinib in refractory non-small cell lung cancer. Clin Cancer Res 2005;11:2244-51 https://doi.org/10.1158/1078-0432.CCR-04-2081
  24. Cappuzzo F, Gregorc V, Rossi E, Cancellieri A, Magrini E, Paties CT, et al. Gefitinib in pretreated non-small-cell lung cancer (NSCLC): analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC. J Clin Oncol 2003;21:2658-63 https://doi.org/10.1200/JCO.2003.01.039
  25. Cappuzzo F, Magrini E, Ceresoli GL, Bartolini S, Rossi E, Ludovini V, et al. Akt phosphorylation and gefitinib efficacy in patients with advanced non-small- cell lung cancer. J Natl Cancer Inst 2004;96:1133-41 https://doi.org/10.1093/jnci/djh217
  26. Dowell JE, Minna JD. Chasing mutations in the epidermal growth factor in lung cancer. N Engl J Med 2005;352:830-2 https://doi.org/10.1056/NEJMe058033
  27. Sordella R, Bell DW, Haber DA, Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 2004;305:1- 163-7 https://doi.org/10.1126/science.305.5681.1
  28. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-39 https://doi.org/10.1056/NEJMoa040938
  29. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, et al. EGF receptor gene mutations are common in lung cancers from 'never smokers' and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004;101:13306-11 https://doi.org/10.1073/pnas.0405220101
  30. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497-500 https://doi.org/10.1126/science.1099314
  31. Han SW, Kim TY, Hwang PG, Jeong S, Kim J, Choi IS, et al. Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small- cell lung cancer patients treated with gefitinib. J Clin Oncol 200523:2493-501 https://doi.org/10.1200/JCO.2005.01.388
  32. Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:e73 https://doi.org/10.1371/journal.pmed.0020073
  33. Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005;352:786-92 https://doi.org/10.1056/NEJMoa044238
  34. Kwak EL, Sordella R, Bell DW, Godin-Heymann N, Okimoto RA, Brannigan BW, et al. Irreversible inhibitorsof the EGF receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci U S A 2005;102:7665-70 https://doi.org/10.1073/pnas.0502860102
  35. Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005;2:e17 https://doi.org/10.1371/journal.pmed.0020017
  36. Thatcher N, Chang A, Parikh P, Pemberton K, Archer V. ISEL: a phase III survival study comparing gefitinib (IRESSA) plus best supportive care (BSC) with placebo plus BSC, in patients with advanced non-small -cell lung cancer (NSCLC) who had received one or two prior chemotherapy regimens. Lung Cancer 2005;49(Suppl 2):4
  37. Pao W, Miller VA. Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and nonsmall-cell lung cancer: current knowledge and future directions. J Clin Oncol 200523:2556-68 https://doi.org/10.1200/JCO.2005.07.799
  38. Sirotnak FM, Zakowski MF, Miller VA, Scher HI, Kris MG. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin Cancer Res 2000;6:4885-92
  39. Ciardiello F, Caputo R, Bianco R, Damiano V, Pomatico G, de Placido S, et al. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res 2000;6:2053-63
  40. Miller VA, Johnson DH, Krug LM, Pizzo B, Tyson L, Perez W, et al. Pilot trial of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib plus carboplatin and paclitaxel in patients with stage IIIB or IV non-small-cell lung cancer. J Clin Oncol 2003;21:2094-100 https://doi.org/10.1200/JCO.2003.12.008
  41. Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, 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 2004;22:777-84 https://doi.org/10.1200/JCO.2004.08.001
  42. Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, 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 2004;22:785-94 https://doi.org/10.1200/JCO.2004.07.215
  43. Cohen MH, Williams GA, Sridhara R, Chen G, McGuinn WD Jr, Morse D, et al. United States Food and Drug Administration Drug Approval summary:Gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res 2004;10:1212-8 https://doi.org/10.1158/1078-0432.CCR-03-0564
  44. Cappuzzo F, Ardizzoni A, Soto-Parra H, Gridelli C, Maione P, Tiseo M, et al. Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC). Lung Cancer 2003;41:227-31 https://doi.org/10.1016/S0169-5002(03)00189-2
  45. Kim MK, Lee KH, Lee JK, Choi JH, Hyun MS. Gefitinib is also active for carcinomatous meningitis in NSCLC. Lung Cancer 200550:265-9 https://doi.org/10.1016/j.lungcan.2005.05.022
  46. Roggero E, Giancarla B, Antonella P, Augusto P. Gefitinib ('Iressa', ZD1839) is active against brain metastases in a 77 year old patient. J Neurooncol 2005;71:277-80 https://doi.org/10.1007/s11060-004-1719-x
  47. Omuro AM, Kris MG, Miller VA, Franceschi E, Shah N, Milton DT, et al. High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinomaafter response to gefitinib. Cancer 2005;103:2344-8 https://doi.org/10.1002/cncr.21033
  48. Perez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, et al. Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. J Clin Oncol 2004;22:3238-47 https://doi.org/10.1200/JCO.2004.11.057
  49. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123-32 https://doi.org/10.1056/NEJMoa050753
  50. Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J, et al. Erlotinib in lung cancer: molecular and clinical predictors of outcome. N Engl J Med 2005;353:133-44 https://doi.org/10.1056/NEJMoa050736
  51. Erlichman C, Boerner SA, Hallgren CG, Spieker R, Wang XY, James CD, et al. The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux. Cancer Res 2001;61:739-48
  52. Peng D, Fan Z, Lu Y, DeBlasio T, Scher H, Mendelsohn J. Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27KIP1 and induces G1 arrest in prostatic cancer cell line DU145. Cancer Res 1996;56:3666-9
  53. Ciardiello F, Bianco R, Damiano V, de Lorenzo S, Pepe S, de Placido S, et al. Antitumor activity of sequential treatment with topotecanand anti-epidermal growth factor receptor monoclonal antibody C225. Clin Cancer Res 1999;5:909-16
  54. Govindan R. Cetuximab in advanced non-small cell lung cancer. Clin Cancer Res 2004;10:4241s-4s https://doi.org/10.1158/1078-0432.CCR-040015
  55. Foon KA, Yang XD, Weiner LM, Belldegrun AS, Figlin RA, Crawford J, et al. Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys 2004;58:984-90 https://doi.org/10.1016/j.ijrobp.2003.09.098
  56. Micke P, Hengstler JG, Ros R, Bittinger F, Metz T, Gebhard S, et al. c-erbB-2 expression in small-cell lung cancer is associated with poor prognosis. Int J Cancer 2001;92:474-9 https://doi.org/10.1002/ijc.1229
  57. Bunn PA Jr, Helfrich B, Soriano AF, Franklin WA, Varella-Garcia M, Hirsch FR, et al. Expression of Her-2/neu in human lung cancer cell lines by immunohistochemistry and fluorescence in situ hybridization and its relationship to in vitro cytotoxicity by trastuzumab and chemotherapeutic agents. Clin Cancer Res 2001;7:3239-50
  58. Langer CJ, Stephenson P, Thor A, Vangel M, Johnson DH. Trastuzumab in the treatment of advanced non-small-cell lung cancer: is there a role? J Clin Oncol 2004;22:1180-7 https://doi.org/10.1200/JCO.2004.04.105
  59. Zinner RG, Glisson BS, Fossella FV, Pisters KM, Kies MS, Lee PM, et al. Trastuzumab in combination with cisplatin and gemcitabine in patients with Her2-overexpressing, untreated, advanced non-small cell lung cancer: report of a phase II trial and findings regarding optimal identification of patients with Her2-overexpressing disease. Lung Cancer 2004;44: 99-110 https://doi.org/10.1016/j.lungcan.2003.09.026
  60. Gatzemeier U, Groth G, Butts C, van Zandwijk N, Shepherd F, Ardizzoni A, et al. Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab trastuzumab in HER2-positive non-small-cell lung cancer. Ann Oncol 2004;15:19-27 https://doi.org/10.1093/annonc/mdh031
  61. Stephens P, Hunter C, Bignell G, Edkins S, Davies H, Teague J, et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 2004;431:525-6
  62. Heinrich MC, Blanke CD, Druker BJ, Corless CL. Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 2002;20:1692-703 https://doi.org/10.1200/JCO.20.6.1692
  63. Kijima T, Maulik G, Ma PC, Tibaldi EV, Turner RE, Rollins B, et al. Regulation of cellular proliferation, cytoskeletal function, and signal transduction through CXCR4 and c-Kit in small cell lung cancer cells. Cancer Res 2002;62:6304-11
  64. Krystal GW, Honsawek S, Kiewlich D, Liang C, Vasile S, Sun L, et al. Indolinone tyrosine kinase inhibitors block Kit activation and growth of small cell lung cancer cells. Cancer Res 2001;61:3660-8
  65. Johnson BE, Fischer T, Fischer B, Dunlop D, Rischin D, Silberman S, et al. Phase II study of imatinib in patients with small cell lung cancer. Clin Cancer Res 2003;9:5880-7
  66. Adjei AA, Mauer A, Bruzek L, Marks RS, Hillman S, Geyer S, et al. Phase II study of the farnesyl transferase inhibitor R115777 in patients with advanced non-small-cell lung cancer. J Clin Oncol 2003;21:1760-6 https://doi.org/10.1200/JCO.2003.09.075
  67. Adjei AA, Croghan GA, Erlichman C, Marks RS, Reid JM, Sloan JA, et al. A Phase I trial of the farnesyl protein transferase inhibitor R115777 in combinationwith gemcitabine and cisplatin in patients with advanced cancer. Clin Cancer Res 2003;9:2520-6
  68. Rudin CM, Holmlund J, Fleming GF, Mani S, Stadler WM, Schumm P, et al. Phase I Trial of ISIS 5132, an antisense oligonucleotide inhibitor of c-raf-1, administered by 24-hour weekly infusion to patients with advanced cancer. Clin Cancer Res 2001;7:1214-20
  69. Blobe GC, Obeid LM, Hannun YA. Regulation of protein kinase C and role in cancer biology. Cancer Metastasis Rev 1994;13:411-31 https://doi.org/10.1007/BF00666107
  70. Koutcher JA, Motwani M, Zakian KL, Li XK, Matei C, Dyke JP, et al. The in vivo effect of bryostatin-1 on paclitaxel-induced tumor growth, mitotic entry, and blood flow. Clin Cancer Res 2000;6:1498-507
  71. Winegarden JD, Mauer AM, Gajewski TF, Hoffman PC, Krauss S, Rudin CM, et al. A phase II study of bryostatin-1 and paclitaxel in patients with advanced non-small cell lung cancer. Lung Cancer 2003;39:191-6 https://doi.org/10.1016/S0169-5002(02)00447-6
  72. Villalona-Calero MA, Ritch P, Figueroa JA, Otterson GA, Belt R, Dow E, et al. A phase I/II study of LY900003, an antisense inhibitor of protein kinase C-alpha, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer. Clin Cancer Res 2004;10:6086-93. https://doi.org/10.1158/1078-0432.CCR-04-0779
  73. Shapiro GI, Supko JG, Patterson A, Lynch C, Lucca J, Zacarola PF, et al. Aphase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer. Clin Cancer Res 2001;7:1590-9
  74. Soh JW, Mao Y, Kim MG, Pamukcu R, Li H, Piazza GA, et al. Cyclic GMP mediates apoptosis induced by sulindac derivatives via activation of c-Jun NH2-terminal kinase 1. Clin Cancer Res 2000;6:4136-41
  75. Thompson WJ, Piazza GA, Li H, Liu L, Fetter J, Zhu B, et al. Exisulind induction of apoptosis involves guanosine 3',5'-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated beta-catenin. Cancer Res 2000;60:3338-42
  76. Witta SE, Gustafson DL, Pierson AS, Menter A, Holden SN, Basche M, et al. A phase I and pharmacokinetic study of exisulind and docetaxel in patients with advanced solid tumors. Clin Cancer Res 2004;10:7229-37 https://doi.org/10.1158/1078-0432.CCR-03-0181
  77. Dy GK, Adjei AA. Novel targets for lung cancer therapy: part II. J Clin Oncol 2002;20:3016-28 https://doi.org/10.1200/JCO.2002.02.112
  78. Tammemagi MC, McLaughlin JR, Bull SB. Meta-analyses of p53 tumor suppressor gene alterations and clinicopathological features in resected lung cancers. Cancer Epidemiol Biomarkers Prev 1999;8:625-34
  79. Moon C, Oh Y, Roth JA. Current status of gene therapy for lung cancer and head and neck cancer. Clin Cancer Res 2003;9:5055-67
  80. Roth JA, Nguyen D, Lawrence DD, Kemp BL, Carrasco CH, Ferson DZ, et al. Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer. Nat Med 1996;2:985-91 https://doi.org/10.1038/nm0996-985
  81. Merritt JA, Roth JA, Logothetis CJ. Clinical evaluation of adenoviral-mediated p53 gene transfer: review of INGN 201 studies. Semin Oncol 2001;28: 105-14 https://doi.org/10.1016/S0093-7754(01)90288-X
  82. Schuler M, Rochlitz C, Horowitz JA, Schlegel J, Perruchoud AP, Kommoss F, et al. A phase I study of adenovirus-mediated wild-type p53 gene transfer in patients with advanced non-small cell lung cancer. Hum Gene Ther 1998;9:2075-82 https://doi.org/10.1089/hum.1998.9.14-2075
  83. Schuler M, Herrmann R, de Greve JL, Stewart AK, Gatzemeier U, Stewart DJ, et al. Adenovirus-memediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-small-cell lung cancer: results of a multicenter phase II study. J Clin Oncol 2001;19:1750-8 https://doi.org/10.1200/JCO.2001.19.6.1750
  84. Sartorius UA, Krammer PH. Upregulation of Bcl-2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines. Int J Cancer 2002;97:584-92 https://doi.org/10.1002/ijc.10096
  85. Zangemeister-Wittke U, Schenker T, Luedke GH, Stahel RA. Synergistic cytotoxicity of bcl-2 antisense oligodeoxynucleotides and etoposide, doxorubicin and cisplatin on small-cell lung cancer cell lines. Br J Cancer 1998;78:1035-42 https://doi.org/10.1038/bjc.1998.624
  86. Ziegler A, Luedke GH, Fabbro D, Altmann KH, Stahel RA, Zangemeister-Wittke U. Induction of apoptosis in small-cell lung cancer cells by an antisense oligodeoxynucleotide targeting the Bcl-2 coding sequence. J Natl Cancer Inst 1997;89:1027-36 https://doi.org/10.1093/jnci/89.14.1027
  87. Rudin CM, Otterson GA, Mauer AM, Villalona-Calero MA, Tomek R, Prange B, et al. A pilot trial of G3139, a bcl-2 antisense oligonucleotide, and paclitaxel in patients with chemorefractory small-cell lung cancer. Ann Oncol 2002;13:539-45 https://doi.org/10.1093/annonc/mdf124
  88. Rudin CM, Kozloff M, Hoffman PC, Edelman MJ, Karnauskas R, Tomek R, et al. Phase I study of G3139, a bcl-2 antisense oligonucleotide, combined with carboplatin and etoposide in patients with small-cell lung cancer. J Clin Oncol 2004;22:1110-7 https://doi.org/10.1200/JCO.2004.10.148
  89. Yatsunami J, Aoki S, Fukuno Y, Kikuchi Y, Kawashima M, Hayashi SI. Antiangiogenic and antitumor effects of tranilast on mouse lung carcinoma cells. Int J Oncol 2000;17:1151-6
  90. Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, 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 2004;22:2184-91 https://doi.org/10.1200/JCO.2004.11.022
  91. Kerr C. Bevacizumab and chemotherapy improves survival in NSCLC. Lancet Oncol 2005;6:266
  92. Sandler AB, Johnson DH, Herbst RS. Anti-vascular endothelial growth factor monoclonals in non-small cell lung cancer. Clin Cancer Res 2004;10:4258s-62s https://doi.org/10.1158/1078-0432.CCR-040023
  93. Herbst RS, Johnson DH, Mininberg E, Carbone DP, Henderson T, Kim ES, 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 200523:2544-55 https://doi.org/10.1200/JCO.2005.02.477
  94. Hida T, Yatabe Y, Achiwa H, Muramatsu H, Kozaki K, Nakamura S, et al. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res 1998;58: 3761-4
  95. Altorki NK, Keresztes RS, Port JL, Libby DM, Korst RJ, Flieder DB, et al. Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non- small-cell lung cancer. J Clin Oncol 2003;21:2645-50 https://doi.org/10.1200/JCO.2003.07.127
  96. Herbst RS, Hess KR, Tran HT, Tseng JE, Mullani NA, Charnsangavej C, et al. Phase I study of recombinant human endostatin in patients with advanced solid tumors. J Clin Oncol 2002;20:3792-803 https://doi.org/10.1200/JCO.2002.11.061
  97. Eder JP Jr, Supko JG, Clark JW, Puchalski TA, Garcia-Carbonero R, Ryan DP, et al. Phase I clinical trial of recombinant human endostatin administered as a short intravenous infusion repeated daily. J Clin Oncol 2002;20:3772-84 https://doi.org/10.1200/JCO.2002.02.082
  98. Herbst RS, Madden TL, Tran HT, Blumenschein GR Jr, Meyers CA, Seabrooke LF, et al. Safety and pharmacokinetic effects of TNP-470, an angiogenesis inhibitor, combined with paclitaxel in patients with solid tumors: evidence for activity in non-small-cell lung cancer. J Clin Oncol 2002;20:4440-7 https://doi.org/10.1200/JCO.2002.04.006
  99. Chambon P. The retinoid signaling pathway: molecular and genetic analyses. Semin Cell Biol 1994;5:115-25 https://doi.org/10.1006/scel.1994.1015
  100. Xu XC, Sozzi G, Lee JS, Lee JJ, Pastorino U, Pilotti S, et al. Suppression of retinoic acid receptor beta in non-small-cell lung cancer in vivo: implications for lung cancer development. J Natl Cancer Inst 1997;89: 624-9 https://doi.org/10.1093/jnci/89.9.624
  101. Brabender J, Danenberg KD, Metzger R, Schneider PM, Lord RV, Groshen S, et al. The role of retinoid X receptor messenger RNA expression in curatively resected non-small cell lung cancer. Clin Cancer Res 2002;8:438-43
  102. Khuri FR, Rigas JR, Figlin RA, Gralla RJ, Shin DM, Munden R, et al. Multi-institutional phase I/II trial of oral bexarotene in combination with cisplatin and vinorelbine in previously untreated patients with advanced non-small-cell lung cancer. J Clin Oncol 2001; 19:2626-37 https://doi.org/10.1200/JCO.2001.19.10.2626
  103. Rizvi N, Hawkins MJ, Eisenberg PD, Yocum RC, Reich SD. Placebo-controlled trial of bexarotene, a retinoid x receptor agonist, as maintenance therapy for patients treated with chemotherapy for advanced non-small-cell lung cancer. Clin Lung Cancer 2001;2:210-5 https://doi.org/10.3816/CLC.2001.n.005
  104. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM. Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 2000;18:1135-49 https://doi.org/10.1200/JCO.2000.18.5.1135
  105. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 1991;64:327-36 https://doi.org/10.1016/0092-8674(91)90642-C
  106. Bissett D, O'Byrne KJ, von Pawel J, Gatzemeier U, Price A, Nicolson M, et al. Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small- cell lung cancer. J Clin Oncol 2005;23:842-9 https://doi.org/10.1200/JCO.2005.03.170
  107. Michael M, Babic B, Khokha R, Tsao M, Ho J, Pintilie M, et al. Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer. J Clin Oncol 1999;17:1802-8 https://doi.org/10.1200/JCO.1999.17.6.1802
  108. Shepherd FA, Giaccone G, Seymour L, Debruyne C, Bezjak A, Hirsh V, et al. Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organization for Research and Treatment of Cancer. J Clin Oncol 2002;20:4434-9 https://doi.org/10.1200/JCO.2002.02.108
  109. Brezicka FT, Olling S, Bergman B, Berggren H, Engstrom CP, Hammarstrom S, et al. Coexpression of ganglioside antigen Fuc-GM1, neural-cell adhesion molecule, carcinoembryonic antigen, and carbohydrate tumor-associated antigen CA 50 in lung cancer. Tumour Biol 1992;13:308-15 https://doi.org/10.1159/000217780
  110. Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A 1993;90: 3539-43 https://doi.org/10.1073/pnas.90.8.3539
  111. Salgia R, Lynch T, Skarin A, Lucca J, Lynch C, Jung K, et al. Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor Immunity in some patients with metastatic non-small-cell lung carcinoma. J Clin Oncol 2003;21:624-30 https://doi.org/10.1200/JCO.2003.03.091
  112. Nemunaitis J, Sterman D, Jablons D, Smith JW 2nd, Fox B, Maples P, et al. Granulocyte-macrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer. J Natl Cancer Inst 2004;96:326-31 https://doi.org/10.1093/jnci/djh028
  113. Assersohn L, Souberbielle BE, O'Brien ME, Archer CD, Mendes R, Bass R, et al. A randomized pilot study of SRL172 (Mycobacterium vaccae) in patients with small cell lung cancer (SCLC) treated with chemotherapy. Clin Oncol (R Coll Radiol) 2002;14:23-7 https://doi.org/10.1053/clon.2001.0030
  114. O'Brien ME, Anderson H, Kaukel E, O'Byrne K, Pawlicki M, von Pawel J, et al. SRL172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer: phase III results. Ann Oncol 2004;15:906-14 https://doi.org/10.1093/annonc/mdh220
  115. Chapman PB, Houghton AN. Induction of IgG antibodies against GD3 ganglioside in rabbits by an anti-idiotypic monoclonal antibody. J Clin Invest 1991;88:186-92
  116. Grant SC, Kris MG, Houghton AN, Chapman PB. Long survival of patients with small cell lung cancer after adjuvant treatment with the anti-idiotypic antibody BEC2 plus Bacillus Calmette-Guerin. Clin Cancer Res 1999;5:1319-23
  117. Lynch TJ Jr, Lambert JM, Coral F, Shefner J, Wen P, Blattler WA, et al. Immunotoxin therapy of small-cell lung cancer: a phase I study of N901-blocked ricin. J Clin Oncol 1997;15:723-34 https://doi.org/10.1200/JCO.1997.15.2.723
  118. Fidias P, Grossbard M, Lynch TJ Jr. A phase II study of the immunotoxin N901-blocked ricin in small-cell lung cancer. Clin Lung Cancer 2002;3:219-22 https://doi.org/10.3816/CLC.2002.n.006
  119. Kelley MJ, Linnoila RI, Avis IL, Georgiadis MS, Cuttitta F, Mulshine JL, et al. Antitumor activity of a monoclonal antibody directed against gastrin-releasing peptide in patients with small cell lung cancer. Chest 1997;112:256-61 https://doi.org/10.1378/chest.112.1.256