Article

You have free access to this content

Lung cancer: New biological insights and recent therapeutic advances†

  1. Suresh S. Ramalingam MD1,
  2. Taofeek K. Owonikoko MD, PhD2,
  3. Fadlo R. Khuri MD3,*

Article first published online: 8 FEB 2011

DOI: 10.3322/caac.20102

Issue

CA: A Cancer Journal for Clinicians

CA: A Cancer Journal for Clinicians

Volume 61, Issue 2, pages 91–112, March/April 2011

Additional Information

How to Cite

Ramalingam, S. S., Owonikoko, T. K. and Khuri, F. R. (2011), Lung cancer: New biological insights and recent therapeutic advances. CA: A Cancer Journal for Clinicians, 61: 91–112. doi: 10.3322/caac.20102

Author Information

  1. 1

    Associate Professor, Department of Hematology and Medical Oncology and The Winship Cancer Institute, Emory University, Atlanta, GA

  2. 2

    Assistant Professor, Department of Hematology and Medical Oncology and The Winship Cancer Institute, Emory University, Atlanta, GA

  3. 3

    Professor and Chair of Hematology and Medical Oncology, Roberto C. Goizueta Distinguished Chair in Translational Cancer Research, Department of Hematology and Medical Oncology and The Winship Cancer Institute, Emory University, Atlanta, GA

*Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365 Clifton Road NE, Atlanta, GA 30322

  1. †

    DISCLOSURES: Supported by National Cancer Institute grant 1PO1 CA116676 and the Distinguished Cancer Clinical Scholar Award by the Georgia Cancer Coalition to all the coauthors. Dr. Ramalingam has served on Ad Hoc Advisory Board for Lilly, Genentech, OSI Pharmaceuticals, Astellas, GlaxoSmithKline, and ImClone. Dr. Khuri serves as a consultant for Pfizer.

Publication History

  1. Issue published online: 8 MAR 2011
  2. Article first published online: 8 FEB 2011

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (767K)

References

  • 1
    Jemal A, Center MM, Desantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010; 19: 1893-1907.
  • 2
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010; 60: 277-300.
    Direct Link:
  • 3
    Owonikoko TK, Ragin CC, Belani CP, et al. Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database. J Clin Oncol. 2007; 25: 5570-5577.
  • 4
    Wakelee HA, Chang ET, Gomez SL, et al. Lung cancer incidence in never smokers. J Clin Oncol. 2007; 25: 472-478.
  • 5
    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.
  • 6
    Rami-Porta R, Ball D, Crowley J, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the T descriptors in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol. 2007; 2: 593-602.
  • 7
    Rusch VW, Crowley J, Giroux DJ, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2007; 2: 603-612.
  • 8
    Postmus PE, Brambilla E, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for revision of the M descriptors in the forthcoming (seventh) edition of the TNM classification of lung cancer. J Thorac Oncol. 2007; 2: 686-693.
  • 9
    Fujii T, Dracheva T, Player A, et al. A preliminary transcriptome map of non-small cell lung cancer. Cancer Res. 2002; 62: 3340-3346.
  • 10
    Garber ME, Troyanskaya OG, Schluens K, et al. Diversity of gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci U S A. 2001; 98: 13784-13789.
  • 11
    Nacht M, Dracheva T, Gao Y, et al. Molecular characteristics of non-small cell lung cancer. Proc Natl Acad Sci U S A. 2001; 98: 15203-15208.
  • 12
    Brambilla E, Travis WD, Colby TV, Corrin B, Shimosato Y. The new World Health Organization classification of lung tumours. Eur Respir J. 2001; 18: 1059-1068.
  • 13
    Roy BC, Kohno T, Iwakawa R, et al. Involvement of LKB1 in epithelial-mesenchymal transition (EMT) of human lung cancer cells. Lung Cancer. 2010; 70: 136-145
  • 14
    Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Cancer. 1995; 75: 2844-2852.
    Direct Link:
  • 15
    Noguchi M. Stepwise progression of pulmonary adenocarcinoma–clinical and molecular implications. Cancer Metastasis Rev. 2010; 29: 15-21.
  • 16
    Doll R, Peto R, Wheatley K, Gray R, Sutherland I. Mortality in relation to smoking: 40 years' observations on male British doctors. BMJ. 1994; 309: 901-911.
  • 17
    Boyle P. Cancer, cigarette smoking and premature death in Europe: a review including the Recommendations of European Cancer Experts Consensus Meeting, Helsinki, October 1996. Lung Cancer. 1997; 17: 1-60.
  • 18
    Beer DG, Kardia SL, Huang CC, et al. Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med. 2002; 8: 816-824.
  • 19
    Bhattacharjee A, Richards WG, Staunton J, et al. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci U S A. 2001; 98: 13790-13795.
  • 20
    Hayes DN, Monti S, Parmigiani G, et al. Gene expression profiling reveals reproducible human lung adenocarcinoma subtypes in multiple independent patient cohorts. J Clin Oncol. 2006; 24: 5079-5090.
  • 21
    Lu Y, Lemon W, Liu PY, et al. A gene expression signature predicts survival of patients with stage I non-small cell lung cancer. PLoS Med. 2006; 3: e467.
  • 22
    Xi L, Lyons-Weiler J, Coello MC, et al. Prediction of lymph node metastasis by analysis of gene expression profiles in primary lung adenocarcinomas. Clin Cancer Res. 2005; 11: 4128-4135.
  • 23
    Guo L, Ma Y, Ward R, Castranova V, Shi X, Qian Y. Constructing molecular classifiers for the accurate prognosis of lung adenocarcinoma. Clin Cancer Res. 2006; 12: 3344-3354.
  • 24
    Lu C, Soria JC, Tang X, et al. Prognostic factors in resected stage I non-small-cell lung cancer: a multivariate analysis of six molecular markers. J Clin Oncol. 2004; 22: 4575-4583.
  • 25
    Truong T, Sauter W, McKay JD, et al. International Lung Cancer Consortium: coordinated association study of 10 potential lung cancer susceptibility variants. Carcinogenesis. 2010; 31: 625-633.
  • 26
    Thorgeirsson TE, Geller F, Sulem P, et al. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature. 2008; 452: 638-642.
  • 27
    Amos CI, Wu X, Broderick P, et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet. 2008; 40: 616-622.
  • 28
    Hung RJ, Christiani DC, Risch A, et al. International Lung Cancer Consortium: pooled analysis of sequence variants in DNA repair and cell cycle pathways. Cancer Epidemiol Biomarkers Prev. 2008; 17: 3081-3089.
  • 29
    Jourenkova-Mironova N, Wikman H, Bouchardy C, et al. Role of glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes in modulating susceptibility to smoking-related lung cancer. Pharmacogenetics. 1998; 8: 495-502.
  • 30
    Brockmoller J, Cascorbi I, Kerb R, Sachse C, Roots I. Polymorphisms in xenobiotic conjugation and disease predisposition. Toxicol Lett. 1998; 102-103: 173-183.
  • 31
    Shields PG. Molecular epidemiology of smoking and lung cancer. Oncogene. 2002; 21: 6870-6876.
  • 32
    Kohno T, Yokota J. How many tumor suppressor genes are involved in human lung carcinogenesis? Carcinogenesis. 1999; 20: 1403-1410.
  • 33
    Mounawar M, Mukeria A, Le Calvez F, et al. Patterns of EGFR, HER2, TP53, and KRAS mutations of p14arf expression in non-small cell lung cancers in relation to smoking history. Cancer Res. 2007; 67: 5667-5672.
  • 34
    Ocak S, Sos ML, Thomas RK, Massion PP. High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications. Eur Respir J. 2009; 34: 489-506.
  • 35
    Hosoe S, Shigedo Y, Ueno K, et al. Detailed deletion mapping of the short arm of chromosome 3 in small cell and non-small cell carcinoma of the lung. Lung Cancer. 1994; 10: 297-305.
  • 36
    Hung J, Kishimoto Y, Sugio K, et al. Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. JAMA. 1995; 273: 1908.
  • 37
    Kohno H, Hiroshima K, Toyozaki T, Fujisawa T, Ohwada H. p53 mutation and allelic loss of chromosome 3p, 9p of preneoplastic lesions in patients with nonsmall cell lung carcinoma. Cancer. 1999; 85: 341-347.
    Direct Link:
  • 38
    Matturri L, Lavezzi AM. Recurrent chromosome alterations in non-small cell lung cancer. Eur J Histochem. 1994; 38: 53-58.
  • 39
    Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007; 448: 561-566.
  • 40
    Soda M, Takada S, Takeuchi K, et al. A mouse model for EML4-ALK-positive lung cancer. Proc Natl Acad Sci U S A. 2008; 105: 19893-19897.
  • 41
    Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009; 27: 4247-4253.
  • 42
    Palmisano WA, Divine KK, Saccomanno G, et al. Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res. 2000; 60: 5954-5958.
  • 43
    Brock MV, Hooker CM, Ota-Machida E, et al. DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med. 2008; 358: 1118-1128.
  • 44
    Owonikoko TK, Ramalingam SS, Kanterewicz B, Balius TE, Belani CP, Hershberger PA. Vorinostat increases carboplatin and paclitaxel activity in non-small-cell lung cancer cells. Int J Cancer. 2010; 126: 743-755.
    Direct Link:
  • 45
    Ramalingam SS, Maitland ML, Frankel P, et al. Carboplatin and Paclitaxel in combination with either vorinostat or placebo for first-line therapy of advanced non-small-cell lung cancer. J Clin Oncol. 2010; 28: 56-62.
  • 46
    Belinsky SA, Nikula KJ, Palmisano WA, et al. Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci U S A. 1998; 95: 11891-11896.
  • 47
    Nuovo GJ, Plaia TW, Belinsky SA, Baylin SB, Herman JG. In situ detection of the hypermethylation-induced inactivation of the p16 gene as an early event in oncogenesis. Proc Natl Acad Sci U S A. 1999; 96: 12754-12759.
  • 48
    Meyerson M, Gabriel S, Getz G. Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet. 2010; 11: 685-696.
  • 49
    McKenna RJ Jr. Lobectomy by video-assisted thoracic surgery with mediastinal node sampling for lung cancer. J Thorac Cardiovasc Surg. 1994; 107: 879-881; discussion 881-872.
  • 50
    McKenna RJ Jr. New approaches to the minimally invasive treatment of lung cancer. Cancer J. 2005; 11: 73-76.
  • 51
    Scott WJ, Allen MS, Darling G, et al. Video-assisted thoracic surgery versus open lobectomy for lung cancer: a secondary analysis of data from the American College of Surgeons Oncology Group Z0030 randomized clinical trial. J Thorac Cardiovasc Surg. 2010; 139: 976-981; discussion 981-973.
  • 52
    [no authors listed]. Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. PORT Meta-analysis Trialists Group. Lancet. 1998; 352: 257-263.
  • 53
    [no authors listed]. 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.
  • 54
    Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010; 303: 1070-1076.
  • 55
    Pennathur A, Luketich JD, Abbas G, et al. Radiofrequency ablation for the treatment of stage I non-small cell lung cancer in high-risk patients. J Thorac Cardiovasc Surg. 2007; 134: 857-864.
  • 56
    Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004; 350: 351-360.
  • 57
    Stephens RJ, Fairlamb D, Gower NH, Maslove L, Milroy R. The Big Lung Trial (BLT): determining the value of cisplatin-based chemotherapy for all patients with non-small cell lung cancer. Preliminary results in the supportive care setting [abstract]. Proc Am Soc Clin Oncol. 2002; 21: 291a.
  • 58
    Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005; 352: 2589-2597.
  • 59
    Strauss GM, Herndon JE 2nd, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008; 26: 5043-5051.
  • 60
    Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006; 7: 719-727.
  • 61
    Kato H, Ichinose Y, Ohta M, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med. 2004; 350: 1713-1721.
  • 62
    Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008; 26: 3552-3559.
  • 63
    Arriagada R, Dunant A, Pignon JP, et al. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant Cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010; 28: 35-42.
  • 64
    Butts CA, Ding K, Seymour L, et al. Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: updated survival analysis of JBR-10. J Clin Oncol. 2010; 28: 29-34.
  • 65
    Pisters KM, Vallieres E, Crowley JJ, et al. Surgery with or without preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer: Southwest Oncology Group Trial S9900, an intergroup, randomized, phase III trial. J Clin Oncol. 2010; 28: 1843-1849.
  • 66
    Scagliotti G, Pastorino U, Vansteenkiste J, et al. A phase III randomized study of surgery alone or surgery plus preoperative gemcitabine-cisplatin in early stage non-small cell lung cancer: follow-up data of Ch.E.S.T [abstract]. J Clin Oncol. 2008; 26: 7399s. Abstract 7508.
  • 67
    Felip E, Rosell R, Maestre JA, et al. Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alone in early-stage non-small-cell lung cancer. J Clin Oncol. 2010; 28: 3138-3145.
  • 68
    Lord RV, Brabender J, Gandara D, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 2002; 8: 2286-2291.
  • 69
    Simon G, Sharma A, Li X, et al. Feasibility and efficacy of molecular analysis-directed individualized therapy in advanced non-small-cell lung cancer. J Clin Oncol. 2007; 25: 2741-2746.
  • 70
    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.
  • 71
    Goss G, Lorimer I, Tsao MS, et al. A phase III randomized, double-blind, placebo-controlled trial of the epidermal growth factor receptor inhibitor gefitinb in completely resected stage IB-IIIA non-small cell lung cancer (NSCLC): NCIC CTG BR. 19 [abstract]. J Clin Oncol. 2010; 28: 516S. Abstract 7005.
  • 72
    Dillman RO, Seagren SL, Propert KJ, et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med. 1990; 323: 940-945.
  • 73
    Le Chevalier T, Arriagada R, Quoix E, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst. 1991; 83: 417-423.
  • 74
    Curran W, Scott C, Langer CJ, et al. Phase III comparison of sequential vs concurrent chemoradiation for patients (Pts) with unresected stage III non-small cell lung cancer (NSCLC): initial report of Radiation Therapy Oncology Group (RTOG) 9410 [abstract]. Proc Am Soc Clin Oncol. 2000; 19: 484a.
  • 75
    Furuse K, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999; 17: 2692-2699.
  • 76
    Albain KS, Crowley JJ, Turrisi AT 3rd, et al. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002; 20: 3454-3460.
  • 77
    Belani CP, Choy H, Bonomi P, et al. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005; 23: 5883-5891.
  • 78
    Perez CA, Stanley K, Rubin P, et al. A prospective randomized study of various irradiation doses and fractionation schedules in the treatment of inoperable non-oat-cell carcinoma of the lung. Preliminary report by the Radiation Therapy Oncology Group. Cancer. 1980; 45: 2744-2753.
    Direct Link:
  • 79
    Blackstock AW, Ho C, Butler J, et al. Phase Ia/Ib chemo-radiation trial of gemcitabine and dose-escalated thoracic radiation in patients with stage III A/B non-small cell lung cancer. J Thorac Oncol. 2006; 1: 434-440.
  • 80
    Socinski MA, Blackstock AW, Bogart JA, et al. Randomized phase II trial of induction chemotherapy followed by concurrent chemotherapy and dose-escalated thoracic conformal radiotherapy (74 Gy) in stage III non-small-cell lung cancer: CALGB 30105. J Clin Oncol. 2008; 26: 2457-2463.
  • 81
    Saunders M, Dische S, Barrett A, Harvey A, Gibson D, Parmar M. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART Steering Committee. Lancet. 1997; 350: 161-165.
  • 82
    Belani CP, Wang W, Johnson DH, et al. Phase III study of the Eastern Cooperative Oncology Group (ECOG 2597): induction chemotherapy followed by either standard thoracic radiotherapy or hyperfractionated accelerated radiotherapy for patients with unresectable stage IIIA and B non-small-cell lung cancer. J Clin Oncol. 2005; 23: 3760-3767.
  • 83
    Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006; 354: 567-578.
  • 84
    Kelly K, Chansky K, Gaspar LE, et al. Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol. 2008; 26: 2450-2456.
  • 85
    Spigel DR, Hainsworth JD, Yardley DA, et al. Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab. J Clin Oncol. 2010; 28: 43-48.
  • 86
    Hanna N, Neubauer M, Yiannoutsos C, et al. Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and U.S. Oncology. J Clin Oncol. 2008; 26: 5755-5760.
  • 87
    Vokes EE, Herndon JE 2nd, Kelley MJ, et al. Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III Non-small-cell lung cancer: Cancer and Leukemia Group B. J Clin Oncol. 2007; 25: 1698-1704.
  • 88
    Govindan R, Bogart J, Wang X, Liu D, Kratzke R, Vokes E. A phase II study of pemetrexed, carboplatin and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small cell lung cancer: CALGB 30407-Early evaluation of feasibility and toxicity [abstract]. J Clin Oncol. 2008; 26: 7401s. Abstract 7518.
  • 89
    Vokes EE, Senan S, Treat JA, Iscoe NA. PROCLAIM: A phase III study of pemetrexed, cisplatin, and radiation therapy followed by consolidation pemetrexed versus etoposide, cisplatin, and radiation therapy followed by consolidation cytotoxic chemotherapy of choice in locally advanced stage III non-small-cell lung cancer of other than predominantly squamous cell histology. Clin Lung Cancer. 2009; 10: 193-198.
  • 90
    Morgensztern D, Goodgame B, Baggstrom MQ, Gao F, Govindan R. The effect of FDG-PET on the stage distribution of non-small cell lung cancer. J Thorac Oncol. 2008; 3: 135-139.
  • 91
    Siddiqui F, Bae K, Langer CJ, et al. The influence of gender, race, and marital status on survival in lung cancer patients: analysis of Radiation Therapy Oncology Group trials. J Thorac Oncol. 2010; 5: 631-639.
  • 92
    Batevik R, Grong K, Segadal L, Stangeland L. The female gender has a positive effect on survival independent of background life expectancy following surgical resection of primary non-small cell lung cancer: a study of absolute and relative survival over 15 years. Lung Cancer. 2005; 47: 173-181.
  • 93
    Harichand-Herdt S, Ramalingam SS. Gender-associated differences in lung cancer: clinical characteristics and treatment outcomes in women. Semin Oncol. 2009; 36: 572-580.
  • 94
    Visbal AL, Williams BA, Nichols FC 3rd, et al. Gender differences in non-small-cell lung cancer survival: an analysis of 4,618 patients diagnosed between 1997 and 2002. Ann Thorac Surg. 2004; 78: 209-215; discussion 215.
  • 95
    Bunn PA Jr. Chemotherapy for advanced non-small-cell lung cancer: who, what, when, why? J Clin Oncol. 2002; 20: 23S-33S.
  • 96
    Rapp E, Pater JL, Willan A, et al. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer–report of a Canadian multicenter randomized trial. J Clin Oncol. 1988; 6: 633-641.
  • 97
    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.
  • 98
    Kelly K, Crowley J, Bunn PA Jr, et al. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non–small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001; 19: 3210-3218.
  • 99
    Wozniak AJ, Crowley JJ, Balcerzak SP, et al. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1998; 16: 2459-2465.
  • 100
    Sandler AB, Nemunaitis J, Denham C, et al. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2000; 18: 122-130.
  • 101
    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.
  • 102
    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.
  • 103
    Fossella F, Pereira JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003; 21: 3016-3024.
  • 104
    Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008; 26: 3543-3551.
  • 105
    Belani CP, Lee JS, Socinski MA, et al. Randomized phase III trial comparing cisplatin-etoposide to carboplatin-paclitaxel in advanced or metastatic non-small cell lung cancer. Ann Oncol. 2005; 16: 1069-1075.
  • 106
    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.
  • 107
    Ramalingam S, Belani CP. State-of-the-art chemotherapy for advanced non-small cell lung cancer. Semin Oncol. 2004; 31( 1 suppl 1): 68-74.
  • 108
    Eismann U, Oberschmidt O, Ehnert M, et al. Pemetrexed: mRNA expression of the target genes TS, GARFT and DHFR correlates with the in vitro chemosensitivity of human solid tumors. Int J Clin Pharmacol Ther. 2005; 43: 567-569.
  • 109
    Righi L, Papotti MG, Ceppi P, et al. Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapy. J Clin Oncol. 2010; 28: 1534-1539.
  • 110
    Scagliotti G, Monica V, Ceppi P, et al. Baseline thymidylate synthase expression according to histological subtypes of non-small cell lung cancer [abstract]. J Clin Oncol. 2009; 27: Page. Abstract 7521.
  • 111
    Socinski M, Bondarenko I, Karaseva N, et al. Results of a randomized, phase III trial of nab-paclitaxel (nab-P) and carboplatin (C) compared with cremophor-based paclitaxel (P) and carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol. 2010; 28: 541S. Abstract 7511.
  • 112
    Desai N, Trieu V, Damascelli B, Soon-Shiong P. SPARC Expression Correlates with Tumor Response to Albumin-Bound Paclitaxel in Head and Neck Cancer Patients. Transl Oncol. 2009; 2: 59-64.
  • 113
    Socinski MA, Schell MJ, Peterman A, et al. Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell lung cancer. J Clin Oncol. 2002; 20: 1335-1343.
  • 114
    Smith IE, O'Brien ME, Talbot DC, et al. Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol. 2001; 19: 1336-1343.
  • 115
    Fidias PM, Dakhil SR, Lyss AP, et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2009; 27: 591-598.
  • 116
    Brodowicz T, Krzakowski M, Zwitter M, et al. Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial. Lung Cancer. 2006; 52: 155-163.
  • 117
    Park JO, Kim SW, Ahn JS, et al. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007; 25: 5233-5239.
  • 118
    Belani CP, Waterhouse D, Ghazal H, et al. Phase III study of maintenance gemcitabine (G) and best supportive care (BSC) versus BSC, following standard combination therapy with gemcitabine-carboplatin (G-Cb) for patients with advanced non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol. 2010; 28: 540S. Abstract 7506.
  • 119
    Westeel V, Quoix E, Moro-Sibilot D, et al. Randomized study of maintenance vinorelbine in responders with advanced non-small-cell lung cancer. J Natl Cancer Inst. 2005; 97: 499-506.
  • 120
    Fidias P, Dakhil SR, Lyss A, et al. Phase III study of immediate versus delayed docetaxel after induction therapy with gemcitabine plus carboplatin in advanced non-small cell lung cancer: updated report with survival [abstract]. J Clin Oncol. 2007; 24: 7388s. Abstract 7516.
  • 121
    Cappuzzo F, Ciuleanu T, Stelmakh L, et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010; 11: 521-529.
  • 122
    Miller V, O'Connor P, Soh C, Kabbinavar F. A randomized, double-blind, placebo-controlled, phase IIIb trial (ATLAS) comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy with B for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol. 2009; 27: Page. Abstract 8002.
  • 123
    Perol M, Chouaid C, Milleron B, et al. Maintenance with either gemcitabine or erlotinib versus observation with predefined second-line treatment after cisplatin-gemcitabine induction chemotherapy in advanced NSCLC: IFCT-GFPC 0502 phase III study [abstract]. J Clin Oncol. 2010; 28: 540S. Abstract 7507.
  • 124
    Ciuleanu T, Brodowicz T, Zielinski C, et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009; 374: 1432-1440.
  • 125
    Soon YY, Stockler MR, Askie LM, Boyer MJ. Duration of chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomized trials. J Clin Oncol. 2009; 27: 3277-3283.
  • 126
    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.
  • 127
    Pirker R, Pereira JR, Szczesna A, et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009; 373: 1525-1531.
  • 128
    Baselga J. The EGFR as a target for anticancer therapy–focus on cetuximab. Eur J Cancer. 2001; 37( suppl 4): S16-S22.
  • 129
    Perez-Soler R, Chachoua A, Hammond LA, et al. Determinants of tumor response and survival with erlotinib in patients with non–small-cell lung cancer. J Clin Oncol. 2004; 22: 3238-3247.
  • 130
    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. 2003; 290: 2149-2158.
  • 131
    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) [corrected]. J Clin Oncol. 2003; 21: 2237-2246.
  • 132
    Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005; 353: 123-132.
  • 133
    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. 2005; 366: 1527-1537.
  • 134
    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. 2004; 350: 2129-2139.
  • 135
    Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304: 1497-1500.
  • 136
    Paz-Ares L, Sanchez JM, Garcia-Velasco A, et al. A prospective phase II trial of erlotinib in advanced non-small cell lung cancer (NSCLC) patients (p) with mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) [abstract]. J Clin Oncol. 2006; 24 . Abstract 7020.
  • 137
    Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. 2009; 361: 958-967.
  • 138
    Hirsch FR, Varella-Garcia M, McCoy J, et al. Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: a Southwest Oncology Group Study. J Clin Oncol. 2005; 23: 6838-6845.
  • 139
    Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009; 361: 947-957.
  • 140
    Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010; 11: 121-128.
  • 141
    Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010; 362: 2380-2388.
  • 142
    Lee JS, Park K, Kim S, et al. A randomized phase III study of gefitinib versus standard chemotherapy (gemcitabine plus cisplatin) as a first-line treatment for never-smokers with advanced or metastatic adenocarcinoma of the lung. J Thorac Oncol. 2009; 4: S283- S284. Abstract PRS 4.
  • 143
    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. 2004; 22: 785-794.
  • 144
    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. 2004; 22: 777-784.
  • 145
    Janne P, Wang SF, Socinski M, et al. Randomized phase II trial of erlotinib (E) alone or in combination with carboplatin/paclitaxel (CP) in never or light former smokers with advanced lung adenocarcinoma: CALGB 30406 [abstract]. J Clin Oncol. 2010; 28: 539S. Abstract 7503.
  • 146
    Hanna N, Lilenbaum R, Ansari R, et al. Phase II trial of cetuximab in patients with previously treated non-small-cell lung cancer. J Clin Oncol. 2006; 24: 5253-5258.
  • 147
    Lynch T, Patel T, Dreisbach L, et al. A randomized phase III study of cetuximab in combination with taxane/carboplatin versus taxane/carboplatin alone as first-line treatment for patients with advanced/metastatic non-small cell lung cancer [abstract]. J Thorac Oncol. 2007; 2: S340. Abstract B3-03.
  • 148
    Khambata-Ford S, Harbison CT, Hart LL, et al. Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2010; 28: 918-927.
  • 149
    Mukohara T, Engelman JA, Hanna NH, et al. Differential effects of gefitinib and cetuximab on non-small-cell lung cancers bearing epidermal growth factor receptor mutations. J Natl Cancer Inst. 2005; 97: 1185-1194.
  • 150
    Kobayashi S, Boggon TJ, Dayaram T, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005; 352: 786-792.
  • 151
    Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007; 316: 1039-1043.
  • 152
    Belani CP. The role of irreversible EGFR inhibitors in the treatment of non-small cell lung cancer: overcoming resistance to reversible EGFR inhibitors. Cancer Invest. 2010; 28: 413-423.
  • 153
    Boyer M, Blackhall F, Park K, et al. Efficacy and safety of PF299804 versus erlotinib (E): a global, randomized phase II trial in patients (pts) with advanced non-small cell lung cancer (NSCLC) after failure of chemotherapy (CT) [abstract]. J Clin Oncol. 2010; 28: 544S. Abstract 7523.
  • 154
    Schiller J, Akerley W, Brugger W, et al. Results from ARQ 197–209: a global randomized placebo-controlled phase II clinical trial of erlotinib plus ARQ 197 versus erlotinib plus placebo in previously treated EGFR inhibitor-naive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol. 2010; 28: 539S. Abstract LBA 7502.
  • 155
    Sequist LV, Gettinger S, Natale NB, et al. A phase II trial of IPI-504 (retaspimycin hydrochloride), a novel Hsp90 inhibitor, in patients with relapsed and/or refractory stage IIIb or stage IV non-small cell lung cancer (NSCLC) stratified by EGFR mutation status [abstract]. J Clin Oncol. 2010 PMID: 20940188.
  • 156
    Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med. 1999; 77: 527-543.
  • 157
    Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009; 27: 1227-1234.
  • 158
    Johnson 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. 2004; 22: 2184-2191.
  • 159
    Ramalingam SS, Dahlberg SE, Langer CJ, et al. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008; 26: 60-65.
  • 160
    Hainsworth J, Herbst R. A phase III, multicenter, placebo-controlled, double-blind, randomized clinical trial to evaluate the efficacy of bevacizumab in combination with erlotinib compared with erlotinib alone for treatment of advanced non-small cell lung cancer after failure of standard first-line chemotherapy (BETA). J Thorac Oncol. 2008; 3: S302.
  • 161
    Socinski MA, Novello S, Brahmer JR, et al. Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. J Clin Oncol. 2008; 26: 650-656.
  • 162
    Schiller JH, Larson T, Ou SH, et al. Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II study. J Clin Oncol. 2009; 27: 3836-3841.
  • 163
    Herbst RS, Sun Y, Eberhardt WE, et al. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010; 11: 619-626.
  • 164
    Schiller J, Lee JW, Hanna N, Traynor AM, Carbone D. A randomized discontinuation phase II study of sorafenib versus placebo in patients with non-small cell lung cancer who have failed at least two prior chemotherapy regimens (ECOG 2501) [abstract]. J Clin Oncol. 2008; 26: 427s. Abstract 8014.
  • 165
    Scagliotti G, Novello S, von Pawel J, et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol. 2010; 28: 1835-1842.
  • 166
    Dowlati A, Gray R, Johnson DH, Schiller J, Brahmer J, Sandler A. Prospective correlative assessment of biomarkers in E4599 randomized phase II/III trial of carboplatin and paclitaxel ± bevacizumab in advanced non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol. 2006; 24: 370S. Abstract 7027.
  • 167
    Beaudry P, Force J, Naumov GN, et al. Differential effects of vascular endothelial growth factor receptor-2 inhibitor ZD6474 on circulating endothelial progenitors and mature circulating endothelial cells: implications for use as a surrogate marker of antiangiogenic activity. Clin Cancer Res. 2005; 11: 3514-3522.
  • 168
    Norden-Zfoni A, Desai J, Manola J, et al. Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor. Clin Cancer Res. 2007; 13: 2643-2650.
  • 169
    Schneider BP, Wang M, Radovich M, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008; 26: 4672-4678.
  • 170
    Zhang W, Dahlberg S, Yang D, et al. Genetic variants in angiogenesis pathway associated with clinical outcome in NSCLC patients (pts) treated with bevacizumab in combination with carboplatin and paclitaxel: subset pharmacogenetic analysis of ECOG 4599 [abstract]. J Clin Oncol. 2009; 27. Abstract 8032.
  • 171
    Bang Y, Kwak EL, Shaw A, et al. Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol. 2010; 28: 6S. Abstract 3.
  • 172
    Sun SY, Fu H, Khuri FR. Targeting mTOR signaling for lung cancer therapy. J Thorac Oncol. 2006; 1: 109-111.
  • 173
    Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007; 356: 2271-2281.
  • 174
    Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008; 372: 449-456.
  • 175
    Ramalingam SS, Harvey RD, Saba N, et al. Phase 1 and pharmacokinetic study of everolimus, a mammalian target of rapamycin inhibitor, in combination with docetaxel for recurrent/refractory nonsmall cell lung cancer. Cancer. 2010; 116: 3903-3909.
    Direct Link:
  • 176
    Soria JC, Shepherd FA, Douillard JY, et al. Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors. Ann Oncol. 2009; 20: 1674-1681.
  • 177
    Ramalingam SS, Sun S, Owonikoko T, Saba N, Khuri F. Targeting the mTOR pathway for treatment of non-small cell lung cancer. Presented at: 2009 NCI Translational Science Meeting; November 5-7, 2009; Vienna, VA.
  • 178
    Karp DD, Paz-Ares LG, Novello S, et al. Phase II study of the anti-insulin-like growth factor type 1 receptor antibody CP-751,871 in combination with paclitaxel and carboplatin in previously untreated, locally advanced, or metastatic non-small-cell lung cancer. J Clin Oncol. 2009; 27: 2516-2522.
  • 179
    Jassem J, Langer C, Karp D, et al. Randomized, open label, phase III trial of figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol. 2010; 28: 539S. Abstract 7500.
  • 180
    Olsen EA, Kim YH, Kuzel TM, et al. Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol. 2007; 25: 3109-3115.
  • 181
    Ramalingam SS, Maitland ML, Frankel P, et al. Carboplatin and Paclitaxel in combination with either vorinostat or placebo for first-line therapy of advanced non-small-cell lung cancer. J Clin Oncol. 2010; 28: 56-62.
  • 182
    Owonikoko TK, Ramalingam SS, Kanterewicz B, Balius TE, Belani CP, Hershberger PA. Vorinostat increases carboplatin and paclitaxel activity in non-small-cell lung cancer cells. Int J Cancer. 2010; 126: 743-755.
    Direct Link:
  • 183
    Port JL, Kent M, Korst RJ, et al. Surgical resection for lung cancer in the octogenarian. Chest. 2004; 126: 733-738.
  • 184
    McVay CL, Pickens A, Fuller C, Houck W, McKenna R Jr. VATS anatomic pulmonary resection in octogenarians. Am Surg. 2005; 71: 791-793.
  • 185
    Gridelli C. The ELVIS trial: a phase III study of single-agent vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer. Elderly Lung Cancer Vinorelbine Italian Study. Oncologist. 2001; 6( suppl 1): 4-7.
  • 186
    Quoix E, Westeel V, Pichon E, et al. Weekly paclitaxel combined with monthly carboplatin versus single-agent therapy in patients age 70 to 89: IFCT-0501 randomized phase III study in advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2010; 28: 5S. Abstract 2.
  • 187
    Vallieres E, Shepherd FA, Crowley J, et al. The IASLC Lung Cancer Staging Project: proposals regarding the relevance of TNM in the pathologic staging of small cell lung cancer in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol. 2009; 4: 1049-1059.
  • 188
    Schreiber D, Rineer J, Weedon J, et al. Survival outcomes with the use of surgery in limited-stage small cell lung cancer: should its role be re-evaluated? Cancer. 2010; 116: 1350-1357.
    Direct Link:
  • 189
    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.
  • 190
    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.
  • 191
    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.
  • 192
    Pandya KJ, Dahlberg S, Hidalgo M, 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.
  • 193
    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.
  • 194
    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.
  • 195
    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.
  • 196
    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.
  • 197
    Kim ES, Herbst RS, Lee J, et al. The BATTLE trial (Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination): personalizing therapy for lung cancer [abstract]. Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; April 17-21, 2010; Washington DC. Abstract LB1.
  • 198
    Bunn PA Jr, Hirsch FR, Doebele RC, Camidge DR, Varella-Garcia M, Franklin W. Biomarkers are here to stay for clinical research and standard care. J Thorac Oncol. 2010; 5: 1113-1115.
View Full Article (HTML) Get PDF (767K)