Emerging drugs for small-cell lung cancer

Expert Opinion on Emerging Drugs

Volumn 14, Issue 4, 2009, Pages 591-606

  Metro, Giulio ^a   Cappuzzo, Federico ^b  

^a REGINA ELENA NATIONAL CANCER INSTITUTE   (Italy)

^b HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

Author keywords

Amrubicin; Angiogenesis; Bcl 2 inhibitors; Picoplatin; Small cell lung cancer; Targeted agents

Indexed keywords

AFLIBERCEPT; AMRUBICIN; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; BEC 2; BELOTECAN; BENDAMUSTINE; BEVACIZUMAB; CARBOPLATIN; CISPLATIN; CYCLOPHOSPHAMIDE; DOXORUBICIN; EPIRUBICIN; ETOPOSIDE; GEFITINIB; IMATINIB; IRINOTECAN; MARIMASTAT; PEMETREXED; PICOPLATIN; PLACEBO; PLATINUM DERIVATIVE; SORAFENIB; SUNITINIB; TANOMASTAT; THALIDOMIDE; TOPOTECAN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANDETANIB; VINCRISTINE;

ANEMIA; BONE MARROW SUPPRESSION; BRAIN METASTASIS; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER RELAPSE; CANCER STAGING; CANCER SURGERY; CANCER SURVIVAL; CHEMOPROPHYLAXIS; CLINICAL EVALUATION; CLINICAL TRIAL; DRUG EFFICACY; DRUG FATALITY; DRUG INHIBITION; DRUG POTENTIATION; DRUG RESEARCH; DRUG TARGETING; HEALTH CARE NEED; HUMAN; LUNG SMALL CELL CANCER; MULTIPLE CYCLE TREATMENT; NEUTROPENIA; RADIATION DOSE; REVIEW; SKULL IRRADIATION; THROMBOCYTOPENIA; TREATMENT OUTCOME; TREATMENT RESPONSE;

ANIMALS; ANTHRACYCLINES; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BRAIN NEOPLASMS; CHEMOTHERAPY, ADJUVANT; COMBINED MODALITY THERAPY; CRANIAL IRRADIATION; DRUG ADMINISTRATION SCHEDULE; DRUG DESIGN; DRUG RESISTANCE, NEOPLASM; EVIDENCE-BASED MEDICINE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; LUNG NEOPLASMS; NEOPLASM RECURRENCE, LOCAL; NEOPLASM STAGING; PROGNOSIS; RADIOTHERAPY DOSAGE; RADIOTHERAPY, ADJUVANT; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SMALL CELL LUNG CARCINOMA; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL;

EID: 71649095728     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728210903206983     Document Type: Review

References (121)

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin 2009; Published online 27 May 2009, doi: 10.3322/caac.20006
2. Bray F, Tyczynski JE, Parkin DM. Going up or coming down? The changing phases of the lung cancer epidemic from 1967 to 1999 in the 15 European union countries. Eur J Cancer 2004;40:96-125
3. Boyle P, Ferlay J. Cancer incidence and mortality in Europe, 2004. Ann Oncol 2005;16:481-488
4. Brownson RC, Chang JC, Davis JR. Gender and histologic type variations in smoking-related risk of lung cancer. Epidemiology 1992;3:61-64
5. Toh CK, Gao F, Lim WT, et al. Differences between small-cell lung cancer and non-small-cell lung cancer among tobacco smokers. Lung Cancer 2007;56:161-166
6. Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006;24:4539-4544
7. Wu YL, Zhou Q. Lung cancer management in the Asia-Pacific region: what's the difference compared with the United States and Europe? Results of the Second Asia Pacific Lung Cancer Conference. J Thorac Oncol 2007;2:574-576
8. Osann KE, Anton-Culver H, Kurosaki T, Taylor T. Sex differences in lung-cancer risk associated with cigarette smoking. Int J Cancer 1993;54:44-48
9. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:1710-1717
10. Giroux DJ, Rami-Porta R, Chansky K, et al. The IASLC Lung Cancer staging project: data elements for the prospective project. J Thorac Oncol 2009;4:679-683
11. 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
12. Sher T, Dy GK, Adjei AA. Small cell lung cancer. Mayo Clin Proc 2008;83:355-367
13. Hodkinson PS, Mackinnon A, Sethi T. Targeting growth factors in lung cancer. Chest 2008;133:1209-1216
14. Pujol JL, Breton JL, Gervais R, et al. Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01. J Clin Oncol 2007;25:3945-3951
15. Lee S, Rudd RM, Woll PJ, et al. Two randomised phase III, double blind, placebo controlled trials of thalidomide in patients with advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). J Clin Oncol 2008;26(Suppl):abstract 8045
16. Fukoka M, Furuse K, Saijo N, et al. Randomised trial of cyclophosphamide, doxorubicin and vincristine versus cisplatin and etoposide versus alternation of these regimens in small cell lung cancer. J Nat Cancer Inst 1991;83:855-861
17. Sundstrøm S, Bremnes RM, Kaasa S, et al. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol 2002;20:4665-4672
18. Chute JP, Chen T, Feigal E, et al. Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress. J Clin Oncol 1999;17:1794-1801
19. Pujol JL, Carestia L, Daurès JP. Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent. Br J Cancer 2000;83:8-15
20. Brahmer JR, Ettinger DS. Carboplatin in the treatment of small cell lung cancer. Oncologist 1998;3:143-154
21. Noda K, Nishiwaki Y, Kawahara M, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 2002;346:85-91
22. Hanna N, Bunn PA Jr, Langer C, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol 2006;24:2038-2043
23. Lara PN Jr, Natale R, Crowley J, et al. Phase III Trial of Irinotecan/Cisplatin Compared With Etoposide/Cisplatin in Extensive-Stage Small-Cell Lung Cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol 2009;27:2530-2535
24. Warde P, Payne D. Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol 1992;10:890-895
25. Pignon JP, Arriagada R, Ihde DC, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 1992;327:1618-1624
26. Takada M, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol 2002;20:3054-3060
27. Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 2004;22:4837-4845
28. De Ruysscher D, Pijls-Johannesma M, Bentzen SM, et al. Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer. J Clin Oncol 2006;24:1057-1063
29. Turrisi AT III, 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;340:265-271
30. Fox W, Scadding JG. Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small-celled or oat-celled carcinoma of bronchus. Ten-year follow-up. Lancet 1973;2:63-65
31. Lad T, Piantadosi S, Thomas P, et al. A prospective randomized trial to determine the benefit of surgical resection of residual disease following response of small cell lung cancer to combination chemotherapy. Chest 1994;106:320S-3S
32. Brock MV, Hooker CM, Syphard JE, et al. Surgical resection of limited disease small cell lung cancer in the new era of platinum chemotherapy: its time has come. J Thorac Cardiovasc Surg 2005;129:64-72
33. Varlotto JM, Recht A, Flickinger JC, et al. Effect of lobectomy on survival in early-stage small cell lung cancer: a retrospective analysis [abstract 7585]. J Clin Oncol 2009;27:15s
34. Aupérin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999;341:476-484
35. Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007;357:664-672
36. Albain KS, Crowley JJ, Hutchins L, et al. Predictors of survival following relapse or progression of small cell lung cancer. Southwest Oncology Group Study 8605 report and analysis of recurrent disease data base. Cancer 1993;72:1184-1191
37. Ardizzoni A, Hansen H, Dombernowsky P, et al. Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol 1997;15:2090-2096
38. Perez-Soler R, Glisson BS, Lee JS, et al. Treatment of patients with small-cell lung cancer refractory to etoposide and cisplatin with the topoisomerase I poison topotecan. J Clin Oncol 1996;14:2785-2790
39. Postmus PE, Berendsen HH, Van Zandwijk N, et al. Retreatment with the induction regimen in small cell lung cancer relapsing after an initial response to short term chemotherapy. Eur J Cancer Clin Oncol 1987;23:1409-1411
40. Vincent M, Evans B, Smith I. First-line chemotherapy rechallenge after relapse in small cell lung cancer. Cancer Chemother Pharmacol 1988;21:45-48 (Pubitemid 18050480)
41. 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;17:658-667
42. Eckardt JR, Von Pawel J, Pujol JL, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 2007;25:2086-2092
43. Onoda S, Masuda N, Seto T, et al. Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301. J Clin Oncol 2006;24:5448-5453
44. Inoue A, Sugawara S, Yamazaki K, et al. Randomized phase II trial comparing amrubicin with topotecan in patients with previously treated small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0402. J Clin Oncol 2008;26:5401-5406
45. Ettinger DS, Jotte R, Lorigan P, et al. Results of a phase II trial of single-agent amrubicin (AMR) in patients with extensive disease small cell lung cancer (ED-SCLC) refractory to first-line platinum-based chemotherapy: an update [abstract 8103]. J Clin Oncol 2009;27:15s
46. Jotte R, Conkling P, Reynolds C, et al. Results of a randomized phase II trial of amrubicin (AMR) versus topotecan (Topo) in patients with extensive-disease small cell lung cancer (ED-SCLC) sensitive to first-line platinum-based chemotherapy [abstract 8028]. J Clin Oncol 2009;27:15s
47. Ettinger DS. Amrubicin for the treatment of small cell lung cancer: does effectiveness cross the Pacific? J Thorac Oncol 2007;2:160-165
48. Yana T, Negoro S, Takada M, et al. Phase II study of amrubicin in previously untreated patients with extensive-disease small cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) study. Invest New Drugs 2007;25:253-258 (Pubitemid 46774694)
49. Ohe Y, Negoro S, Matsui K, et al. Phase I-II study of amrubicin and cisplatin in previously untreated patients with extensive-stage small-cell lung cancer. Ann Oncol 2005;16:430-436
50. Kawamura-Akiyama Y, Kusaba H, Kanzawa F, et al. Non-cross resistance of ZD0473 in acquired cisplatin-resistant lung cancer cell lines. Lung Cancer 2002;38:43-50
51. Treat J, Schiller J, Quoix E, et al. ZD0473 treatment in lung cancer: an overview of the clinical trial results. Eur J Cancer 2002;38:S13-8
52. Eckardt JR, Bentsion DL, Lipatov ON, et al. Phase II study of picoplatin as second-line therapy for patients With small-cell lung cancer. J Clin Oncol 2009;27:2046-2051
53. Poniard completes patient enrollment target in phase 3 SPEAR trial of Picoplatin in Small Cell Lung Cancer. Available from: http://investor.poniard. com/releasedetail.cfm?ReleaseID=372892 [Last accessed 4 June 2009]
54. Lee JH, Lee JM, Kim JK, et al. Antitumor activity of 7-[2(N- isopropylamino)ethyl]-(20S)-camptothecin, CKD602, as a potent DNA topoisomerase I inhibitor. Arch Pharm Res 1998;21:581-590
55. Lee DH, Kim SW, Suh C, et al. Belotecan, new camptothecin analogue, is active in patients with small-cell lung cancer: results of a multicenter early phase II study. Ann Oncol 2008;19:123-127
56. Trial of Belotecan/Cisplatin in chemotherapy naive small cell Lung Cancer patient. Available at: http://clinicaltrials.gov/ct2/results?term=NCT00826644 [Last accessed 4 June 2009]
57. Belotecan and Cisplatin in treating patients with previously untreated, extensive-stage small cell Lung Cancer. Available from: http://clinicaltrials. gov/ct2/results?term=NCT00754858 [Last accessed 4 June 2009]
58. Strumberg D, Harstrick A, Doll K, et al. Bendamustine hydrochloride activity against doxorubicin-resistant human breast carcinoma cell lines. Anticancer Drugs 1996;7:415-421
59. Leoni LM, Bailey B, Reifert J, et al. Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res 2008;14:309-317
60. Schmittel A, Knödler M, Hortig P, et al. Phase II trial of second-line bendamustine chemotherapy in relapsed small cell lung cancer patients. Lung Cancer 2007;55:109-113
61. Köster W, Heider A, Niederle N, et al. Phase II trial with carboplatin and bendamustine in patients with extensive stage small-cell lung cancer. J Thorac Oncol 2007;2:312-316
62. Bendamustine with Irinotecan followed by Etoposide/Carboplatin for patients with extensive stage small cell Lung Cancer. Available from: http://clinicaltrials.gov/ct2/results?term=NCT00856830 [Last accessed 4 June 2009]
63. Study to determine the efficacy of Bendamustin in patients with recurrent Small Cell Lung Cancer (SCLC). Available from: http://clinicaltrials.gov/ct2/ results?term=NCT00168922 [Last accessed 4 June 2009]
64. Bozcuk H, Artac M, Ozdogan M, Savas B. Does maintenance/consolidation chemotherapy have a role in the management of small cell lung cancer (SCLC)? A metaanalysis of the published controlled trials. Cancer 2005;104:2650-2657
65. Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med 1999;77:527-543 (Pubitemid 29426311)
66. Kukk E, Lymboussaki A, Taira S, et al. VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Development 1996;122:3829-3837
67. Dowell JE, Amirkhan RH, Lai WS, et al. Survival in small cell lung cancer is independent of tumor expression of VEGF and COX-2. Anticancer Res 2004;24:2367-2373
68. Lucchi M, Mussi A, Fontanini G, et al. Small cell lung carcinoma (SCLC): the angiogenic phenomenon. Eur J Cardiothorac Surg 2002;21:1105-1110
69. Presta LG, Chen H, O'Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997;57:4593-4599
70. Sandler A, Szwaric S, Dowlati A, et al. A phase II study of cisplatin (P) plus etoposide (E) plus bevacizumab (B) for previously untreated extensive stage small cell lung cancer (SCLC) (E3501): a trial of the Eastern Cooperative Oncology Group [abstract 7564]. J Clin Oncol 2007;25:18s
71. Ready N, Dudek AZ, Wang XF, et al. CALGB 30306: A phase II study of cisplatin (C), irinotecan (I) and bevacizumab (B) for untreated extensive stage small cell lung cancer (ES-SCLC) [abstract 7563]. J Clin Oncol 2007;25:18s
72. A study of Bevacizumab in previously untreated extensive-stage small cell Lung Cancer (SALUTE). Available from: http://clinicaltrials.gov/ct2/results? term=NCT00403403 [Last accessed 4 June 2009]
73. Spigel DR, Hainsworth JD, Farley C, et al. Tracheoesophageal (TE) fistula development in a phase II trial of concurrent chemoradiation (CRT) and bevacizumab (B) in limited-stage small-cell lung cancer (LS-SCLC). J Clin Oncol 2008;26(Suppl):abstract 7554
74. Abrams TJ, Lee LB, Murray LJ, et al. SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther 2003;2:471-478
75. Wedge SR, Kendrew J, Hennequin LF, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res 2005;65:4389-4400
76. Arnold AM, Smylie M, Ding K, et al. Randomized phase II study of maintenance vandetanib (ZD6474) in small cell lung cancer (SCLC) patients who have a complete or partial response to induction therapy: NCIC CTG BR.20 [abstract 7522]. J Clin Oncol 2007;25:18s
77. Press MF, Lenz HJ. EGFR, HER2 and VEGF pathways: validated targets for cancer treatment. Drugs 2007;67:2045-2075
78. Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell 2000;103:253-262
79. Pandya KJ, Dahlberg S, Hidalgo MC, et al. A randomized, phase II trial of two dose levels of temsirolimus (CCI-779) in patients with extensive-stage small-cell lung cancer who have responding or stable disease after induction chemotherapy: a trial of the Eastern Cooperative Oncology Group (E1500). J Thorac Oncol 2007;2:1036-1041
80. Kotsakis AP, Tarhini A, Petro D, et al. Phase II study of RAD001 (everolimus) in previously treated small cell lung cancer (SCLC) [abstract 8107]. J Clin Oncol 2009;27:15s
81. Mondesire WH, Jian W, Zhang H, et al. Targeting mammalian target of rapamycin synergistically enhances chemotherapy-induced cytotoxicity in breast cancer cells. Clin Cancer Res 2004;10:7031-7042
82. Beuvink I, Boulay A, Fumagalli S, et al. The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation. Cell 2005;120:747-759
83. Everolimus, Carboplatin, and Etoposide in treating patients with small cell Lung Cancer or other advanced solid tumors. Available from: http://clinicaltrials.gov/ct2/results?term=NCT00807755 [Last accessed 4 June 2009]
84. Safety of RAD001 in combination with Cisplatin and Etoposide in Lung Cancer patients. Available from: http://clinicaltrials.gov/ct2/results?term= NCT00466466 [Last accessed 4 June 2009]
85. Khandwala HM, McCutcheon IE, Flyvbjerg A, et al. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 2000;21:215-244
86. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 1995;16:3-34
87. Leroith D, Werner H, Beitner-Johnson D, et al. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 1995;16:143-163
88. Warshamana-Greene GS, Litz J, Buchdunger E, et al. The insulin-like growth factor-I receptor kinase inhibitor, NVP-ADW742, sensitizes small cell lung cancer cell lines to the effects of chemotherapy. Clin Cancer Res 2005;11:1563-1571
89. Tolcher AW, Rothenberg ML, Rodon J, et al. A phase I pharmacokinetic and pharmacodynamic study of AMG 479, a fully human monoclonal antibody against insulin-like growth factor type 1 receptor (IGF-1R), in advanced solid tumors [abstract 3002]. J Clin Oncol 2007;25:18s
90. Rowinsky EK, Youssoufian H, Tonra JR, et al. IMC-A12, a human IgG1 monoclonal antibody to the insulin-like growth factor I receptor. Clin Cancer Res 2007;13:5549s-55s
91. Atzori F, Tabernero J, Cervantes A, et al. A phase I, pharmacokinetic (PK) and pharmacodynamic (PD) study of weekly (qW) MK-0646, an insulin-like growth factor-1 receptor (IGF1R) monoclonal antibody (MAb) in patients (pts) with advanced solid tumors. J Clin Oncol 2008;26(Suppl):abstract 3519
92. A Phase 1b/2 Trial of AMG 479 or AMG 102 in combination with platinum-based chemotherapy as first-line treatment for extensive stage small cell Lung Cancer. Available from: http://clinicaltrials.gov/ct2/results?term= NCT00791154 [Last accessed 4 June 2009]
93. Cisplatin and Etoposide Phosphate with or without GDC-0449 or Cixutumumab in treating patients with extensive-stage small cell Lung Cancer. Available from: http://clinicaltrials.gov/ct2/results?term=NCT00887159 [Last accessed 4 June 2009]
94. MK-0646, Etoposide, and Cisplatin in treating patients with extensive-stage small cell Lung Cancer. Available from: http://clinicaltrials. gov/ct2/results?term=NCT00869752 [Last accessed 4 June 2009]
95. Giehl K. Oncogenic Ras in tumour progression and metastasis. Biol Chem 2005;386:193-205
96. Khanzada UK, Pardo OE, Meier C, et al. Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling. Oncogene 2006;25:877-887
97. Irinotecan/Cisplatin plus Simvastatin in Extensive Disease-Small Cell Lung Cancer (ED-SCLC). Available from: http://clinicaltrials.gov/ct2/results? term=NCT00452634 [Last accessed 4 June 2009]
98. Etoposide and Cisplatin or Carboplatin as first-line chemotherapy with or without Pravastatin in treating patients with small cell Lung Cancer. Available from: http://clinicaltrials.gov/ct2/results?term=NCT00433498 [Last accessed 4 June 2009]
99. Zinkel S, Gross A, Yang E. BCL2 family in DNA damage and cell cycle control. Cell Death Differ 2006;13:1351-1359
100. Reed JC. Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance. Curr Opin Oncol 1995;7:541-546
101. Ikegaki N, Katsumata M, Minna J, Tsujimoto Y. Expression of bcl-2 in small cell lung carcinoma cells. Cancer Res 1994;54:6-8
102. 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;97:584-592
103. Rudin CM, Otterson GA, Mauer AM, 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;13:539-545
104. Rudin CM, Kozloff M, Hoffman PC, 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;22:1110-1117
105. Rudin CM, Salgia R, Wang X, et al. Randomized phase II Study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer: CALGB 30103. J Clin Oncol 2008;26:870-876
106. Gossypol in treating patients with recurrent extensive-stage small cell Lung Cancer. Available from: http://clinicaltrials.gov/ct2/results?term= NCT00773955 [Last accessed 4 June 2009]
107. Gossypol, Cisplatin, and Etoposide in treating patients with advanced solid tumors or extensive stage small cell Lung Cancer. Available from: http://clinicaltrials.gov/ct2/results?term=+%09NCT00544596 [Last accessed 4 June 2009]
108. A phase I/II study of Carboplatin and Etoposide with or without Obatoclax in Extensive-Stage Small Cell Lung Cancer (ES-SCLC). Available from: http://clinicaltrials.gov/ct2/results?term=NCT00682981 [Last accessed 4 June 2009]
109. Obatoclax Mesylate and Topotecan in treating patients with relapsed or refractory small cell Lung Cancer or advanced solid tumors. Available from: http://clinicaltrials.gov/ct2/results?term=NCT00521144 [Last accessed 4 June 2009]
110. A phase 1/2a study of ABT-263 in subjects with Small Cell Lung Cancer (SCLC) or other non-hematological malignancies. Available from: http://clinicaltrials.gov/ct2/results?term=NCT00445198 [Last accessed 4 June 2009]
111. Brown AB, Rudin C, Rizvi N, et al. Phase I study of obatoclax mesylate (GX15-070MS), a bcl-2 antagonist, plus topotecan in relapsed small cell lung carcinoma and other solid tumors [abstract 3504]. J Clin Oncol 2009;27:15s
112. Chiappori A, Schreeder MT, Moezi MM, et al. A phase Ib trial of Bcl-2 inhibitor obatoclax in combination with carboplatin and etoposide for previously untreated patients with extensive-stage small cell lung cancer (ES-SCLC) [abstract 3576]. J Clin Oncol 2009;27:15s
113. Heist RS, Fain J, Chinnasami B, et al. A phase I/II (P1/P2) study of AT-101 in combination with topotecan (T) in patients with relapsed or refractory small cell lung cancer (SCLC) after prior platinum-containing first-line chemotherapy [abstract 8106]. J Clin Oncol 2009;27:15s
114. Ma PC, Tretiakova MS, Nallasura V, et al. Downstream signalling and specific inhibition of c-MET/HGF pathway in small cell lung cancer: implications for tumour invasion. Br J Cancer 2007;97:368-377
115. Ma PC, Kijima T, Maulik G, et al. c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 2003;63:6272-6281
116. Watkins DN, Berman DM, Burkholder SG, et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 2003;422:313-317
117. Vestergaard J, Pedersen MW, Pedersen N, et al. Hedgehog signaling in small-cell lung cancer: frequent in vivo but a rare event in vitro. Lung Cancer 2006;52:281-290
118. Lara P, Chansky K, Shibata T, et al. Cisplatin + irinotecan versus cisplatin + etoposide in extensive stage small cell lung cancer (E-SCLC): Final "common arm": comparative outcomes analysis of JCOG 9511 and SWOG 0124 [abstract 8027]. J Clin Oncol 2009;27:15s
119. Socinski MA, Smit EF, Lorigan P, et al. Phase III study of pemetrexed plus carboplatin (PC) versus etoposide plus carboplatin (EC) in chemonaive patients (pts) with extensive-stage disease small cell lung cancer (ED-SCLC): Interim results. J Clin Oncol 2008;26(Suppl):abstract NSA)
120. Scagliotti G, Monica V, Ceppi P, et al. Baseline thymidylate synthase expression according to histological subtypes of non-small cell lung cancer [abstract 7521]. J Clin Oncol 2009;27:15s
121. Ceppi P, Volante M, Saviozzi S, et al. Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase. Cancer 2006;107:1589-1596