Anti-angiogenic agents in the treatment of lung cancer: Indications and toxicities;Thérapeutiques antiangiogéniques dans le cancer bronchique: indications et toxicités

Revue des Maladies Respiratoires

Volumn 29, Issue 2, 2012, Pages 161-177

  Clement Duchene C ^a   Godbert, B ^a   Martinet, Y ^a  

^a UNIVERSITY HOSPITAL OF NANCY   (France)

Author keywords

Anti angiogenic agents; Lung cancer; Toxicities; Vascular Disrupting Agents; VEGF

Indexed keywords

AFLIBERCEPT; ANGIOGENESIS INHIBITOR; AXITINIB; BEVACIZUMAB; CEDIRANIB; MITOFLAXONE 2 DIETHYLAMINOETHYL ESTER; MOTESANIB; N [2 [(4 HYDROXYPHENYL)AMINO] 3 PYRIDINYL] 4 METHOXYBENZENESULFONAMIDE; N ACETYLCOLCHINOL PHOSPHATE; PAZOPANIB; PROTEIN TYROSINE KINASE INHIBITOR; RECOMBINANT ENDOSTATIN; SORAFENIB; SUNITINIB; THALIDOMIDE; VADIMEZAN; VANDETANIB; VASCULOTROPIN; VATALANIB;

ADVANCED CANCER; ANEMIA; ANOREXIA; ANTIANGIOGENIC THERAPY; ANXIETY; ASTHENIA; ATAXIA; BONE PAIN; CANCER MORTALITY; CANCER SURVIVAL; CARDIOTOXICITY; CAUSE OF DEATH; CHOLESTATIC HEPATITIS; CONSTIPATION; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DRUG INDICATION; DRUG TOLERABILITY; DYSPNEA; EPISTAXIS; FATIGUE; FEBRILE NEUTROPENIA; HEADACHE; HEART MUSCLE ISCHEMIA; HEMOPTYSIS; HUMAN; HYPERTENSION; HYPONATREMIA; HYPOTENSION; LEUKOENCEPHALOPATHY; LUNG CANCER; LUNG EMBOLISM; LUNG NON SMALL CELL CANCER; MALAISE; MYALGIA; MYCOSIS; NAUSEA; NEUTROPENIA; NOSE INJURY; PAIN; PNEUMONIA; PROTEINURIA; QT PROLONGATION; RASH; REVIEW; SIDE EFFECT; SINUSITIS; THORAX PAIN; THROMBOEMBOLISM; TREATMENT RESPONSE; VISUAL DISORDER; VOMITING;

ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; HUMANS; LUNG NEOPLASMS; PROTEIN KINASE INHIBITORS; VASCULAR ENDOTHELIAL GROWTH FACTORS;

EID: 84859105797     PISSN: 07618425     EISSN: 17762588     Source Type: Journal    
DOI: 10.1016/j.rmr.2011.06.017     Document Type: Review

References (144)

1. http://www.iarc.fr.
2. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-49.
3. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:1710-7.
4. Bunn Jr PA, Thatcher N. Systemic treatment for adVanced (stage IIIb/IV) non-small cell lung cancer: more treatment options ; more things to consider. Conclusion. Oncologist 2008;13:37-46.
5. Depierre A, Lagrange JL, Theobald S, et al. Standards, Options and Recommendations for the management of patients with non-small-cell lung carcinoma (2000). Br J Cancer 2003;89:S35-49.
6. Clement-Duchene C, Wakelee H. Antiangiogenic agents and vascular disrupting agents for the treatment of lung cancer: a review. J Thorac Oncol 2010;5:129-39.
7. Gasparini G, Longo R, Fanelli M, et al. Combination of antiangiogenic therapy with other anticancer therapies: results, challenges, and open questions. J Clin Oncol 2005;23:1295-311.
8. Cabebe E, Wakelee H. Role of anti-angiogenesis agents in treating NSCLC: focus on bevacizumab and VEGFR tyrosine kinase inhibitors. Curr Treat Options Oncol 2007;8:15-27.
9. Herbst RS, Sandler A. Bevacizumab and erlotinib: a promising new approach to the treatment of adVanced NSCLC. Oncologist 2008;13:1166-76.
10. Wakelee H. Antibodies to vascular endothelial growth factor in non-small cell lung cancer. J Thorac Oncol 2008;3:S113-118.
11. Wakelee HA, Schiller JH. Targeting angiogenesis with vascular endothelial growth factor receptor small-molecule inhibitors: novel agents with potential in lung cancer. Clin Lung Cancer 2005;7:S31-38.
12. Wheatley-Price P, Shepherd FA. Targeting angiogenesis in the treatment of lung cancer. J Thorac Oncol 2008;3:1173-84.
13. 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;355:2542-50.
14. Kelland LR. Targeting established tumor vasculature: a novel approach to cancer treatment. Current Cancer Therapy Treatment 2005;1:1-9.
15. Folkman J. Tumor angiogenesis: therapeutic implications. Engl J N Med 1971;285:1182-6.
16. Keck PJ, Hauser SD, Krivi G, et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989;246:1309-12.
17. Pepper MS, Montesano R, Mandriota SJ, et al. Angiogenesis: a paradigm for balanced extracellular proteolysis during cell migration and morphogenesis. Enzyme Protein 1996;49:138-62.
18. Robinson CJ, Stringer SE. The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 2001;114:853-65.
19. Bremnes RM, Camps C, Sirera R. Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer 2006;51:143-58.
20. Lyden D, Hattori K, Dias S, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001;7:1194-201.
21. 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;57:4593-9.
22. 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;22:2184-91.
23. Brahmer JR, Gray R, Schiller JH. ECOG 4599 phase III trial of carboplatin and paclitaxel bevacizumab: subset analysis of survival by gender. J Clin Oncol 2006; 24:abstract 7036.
24. Wakelee HA, Dahlberg SE, Brahmer JR. Increased benefit from bevacizumab (BEV) in younger women with adVanced NSCLC on Eastern Cooperative Oncology Group (ECOG) E4599. J Thorac Oncol 2008; 3:abstract 131.
25. Cohen MH, Gootenberg J, Keegan P, et al. FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of adVanced/metastatic recurrent nonsquamous non-small cell lung cancer. Oncologist 2007;12:713-8.
26. Besse B, Lasserre SF, Compton P, et al. Bevacizumab safety in patients with central nervous system metastases. Clin Cancer Res 2010;16:269-78.
27. Socinski MA, Langer CJ, Huang JE, et al. Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. J Clin Oncol 2009;27:5255-61.
28. Reck M, von Pawel J, Zatlouka P. First-line Bevacizumab combined with Cisplatin/Gencitabine (CG) in patients (pts) with adVanced or recurrent non-squamous, non-small cell lung cancer (NSCLC): AVAIL (BO17704), a phase III randomized study. J Thorac Oncol 2008;12:1487-8.
29. 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;27:1227-34.
30. Hainsworth J, Herbst R. A phase III, multicenter, placebocontrolled, double-blind, randomized clinical trial to evaluate the eficacity of Bevacizumab (AVASTIN®) in combination with Erlotinib (TARCEVA®) compared with Erlotinib alone treatment of adVanced non-small cell lung cancer after failure of standard first-line chemotherapy (BETA). J Thorac Oncol 2008;12:1487.
31. Kabbinavar FF, Miller VA, Johnson BE, et al. Overall survival (OS) in ATLAS, a phase IIIb trial comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy (chemo) with B for first-line treatment of locally adVanced, recurrent, or metastatic non-small cell lung cancer (NSCLC). J Clin Oncol 2010;28:15s. (suppl; abstract 7526).
32. Davila E, Lilenbaum R, Raez L. Phase II trial of oxaliplatin and gemcitabine with bevacizumab in first-line adVanced nonsmall cell lung cancer (NSCLC). J Clin Oncol 2006; 24:abstract 17009.
33. Heist RS, Fidias P, Huberman M. Phase II trial of oxaliplatin, pemetrexed, and bevacizumab in previously-treated adVanced non-small cell lung cancer (NSCLC). J Clin Oncol 2007;25:abstract 7700.
34. Kraut MJ. Phase II study of gemcitabine and carboplatin plus bevacizumab for stage III/IV non-small cell lung cancer: preliminary safety data. J Clin Oncol 2006; 24:abstract 17091.
35. Patel JD, Hensing TA, Rademaker A, et al. Phase II study of pemetrexed and carboplatin plus bevacizumab with maintenance pemetrexed and bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer. J Clin Oncol 2009;27:3284-9.
36. Waples JM, Auerbach M, Boccia R. A phase II study of oxaliplatin and pemetrexed plus bevacizumab in adVanced non-squamous non-small cell lung cancer. J Clin Oncol 2007; 25:abstract 18025.
37. William WN, Kies MS, Fossella FV. Phase II study of bevacizumab in combination with docétaxel and carboplatin in patients with metastatic non-small cell lung cancer (NSCLC). J Clin Oncol 2007;25:abstract 18098.
38. Gandara D, Kim ES, Herbst RS. S0536: Carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab maintenance in adVanced non-small cell lung cancer (NSCLC): A SWOG phase II study. J Clin Oncol 2009; 27:abstract 8015.
39. Halimi JM, Azizi M, Bobrie G, et al. Vascular and renal effects of anti-angiogenic therapy. Nephrol Ther 2008;4:602-15.
40. 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;26:60-5.
41. Leighl NB, Zatloukal P, Mezger J. Efficacy and safety of first-line bevacizumab (Bv) and cisplatin/gemcitabine (CG) in elderly patients (pts) with adVanced non-small cell lung cancer (NSCLC) in the BO17704 study (AVAiL). J Clin Oncol 2009;27:abstract 8050.
42. Akerley W, Hainsworth J, Oh Y. Safety of bevacizumab therapy in subjects with brain metastases due to non-small cell lung cancer (NSCLC). J Thorac Oncol 2007;2:abstract PD463-3-3.
43. Hainsworth JD, Fang L, Huang JE, et al. BRIDGE: an open-label phase II trial evaluating the safety of bevacizumab + carboplatin/paclitaxel as first-line treatment for patients with adVanced, previously untreated, squamous nonsmall cell lung cancer. J Thorac Oncol 2011;6:109-14.
44. Fehrenbacher L, O'Neill V, Belani C, et al. A phase II, multicenter, randomized clinical trial to evaluate the efficacy and safety of bevacizumab in combination with either chemotherapy (docétaxel or pemetrexed) or erlotinib hydrochloride compared with chemotherapy alone for treatment of recurrent or refractory non-small cell lung cancer. J Clin Oncol 2006;24:379S.
45. Shord SS, Bressler LR, Tierney LA, et al. Understanding and managing the possible adverse effects associated with bevacizumab. Am J Health Syst Pharm 2009;66:999-1013.
46. Zhu X, Wu S, Dahut WL, et al. Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and metaanalysis. Am J Kidney Dis 2007;49:186-93.
47. NCCN Clinical Practice Guidelines in Oncology. Available at www.nccn.org.
48. Izzedine H, Ederhy S, Goldwasser F, et al. Management of hypertension in angiogenesis inhibitor-treated patients. Ann Oncol 2009;20:807-15.
49. Thanigaimani S, Mangoni A, Karapetis CS, et al. Anti-VEGF drugs, endothelial dysfunction, and hypertension: Is there relationship? J Clin Oncol 2010;28:abstract 13585.
50. Boehm S, Rothermundt C, Hess D, et al. Antiangiogenic drugs in oncology: a focus on drug safety and the elderly -a minireview. Gerontology 2010;56:303-9.
51. Starling N, Cunningham D. Complications of vascular endothelial growth factor inhibitors in colorectal cancer. In: DeVita Jr VT, Hellman S, Rosenberg SA, editors. Principles and practice of oncology. Philadelphia: Lippincott, Williams and Wilkins; 2005, p. 1-15.
52. Nalluri SR, Chu D, Keresztes R, et al. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 2008;300:2277-85.
53. Gordon MS, Cunningham D. Managing patients treated with bevacizumab combination therapy. Oncology 2005;69:25-33.
54. Li I, Stitt L, Whiston F, Alkhayyat SS, et al. Wound complications in neoadjuVant versus adjuVant treatment of operable rectal cancer (ORC). J Clin Oncol 2010; 28:abstract14099.
55. Fakih MG, Lombardo JC. Bevacizumab-induced nasal septum perforation. Oncologist 2006;11:85-6.
56. Mailliez A, Baldini C, Van JT, et al. Nasal septum perforation: a side effect of bevacizumab chemotherapy in breast cancer patients. Br J Cancer 2010;103:772-5.
57. Lenz HJ. Management and preparedness for infusion and hypersensitivity reactions. Oncologist 2007;12: 601-9.
58. Hapani S, Ranpura V, Wu S. Risk of fatal adverse events with bevacizumab in cancer patients treated with chemotherapy: A meta-analysis. J Clin Oncol 2010; 28:abstract19500.
59. Crino L, Dansin E, Garrido P, et al. Safety and efficacy of firstline bevacizumab-based therapy in adVanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study. Lancet Oncol 2010;11:733-40.
60. Braehmer J, Spigel D, Garst JL, et al. The impact of tumor histology on effectiveness in bevacizumab (BV) treated patients (PTS) with adVanced non-small cell lung cancer (NSCLC): Results from ARIES, a BV obserational cohort study (OCS). Ann Oncol 2010;21;viii122-61, 426P.
61. Fischbach NA, Wozniak A, Kumar P, et al. Clinical outcomes (COS) by sex in non-small cell lung cancer (NSCLC) patients (PTS): preliminary results from ARIES, a bevacizumab (BV) observational cohort study (OCS). Ann Oncol 2010;21;viii122-61, 425P.
62. Soria JC, Mauguen A, Reck M, et al. Meta-analysis of randomized phase II/III trials adding bevacizumab to platinbased chemotherapy as 1ST-line treatment in patients with adVanced non-small cell lung cancer (NSCLC). Ann Oncol 2010;21;viii122-61, 437P.
63. Camidge DR, Eckhardt SG, Diab S. A phase I dose-escalation study of weekly IMC-1121B, a fully human anti-vascular endothelial growth factor receptor 2 (VEGFR2) IgG1 monoclonal antibody (Mab), in patients (pts) with adVanced cancer. J Clin Oncol 2006;24:abstract 3032.
64. O'Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997;88:277-85.
65. Yang L, Wang JW, Sun Y, et al. Randomized phase II trial on escalated doses of Rh-endostatin (YH-16) for adVanced non-small cell lung cancer. Zhonghua Zhong Liu Za Zhi 2006;28:138-41.
66. Sun Y, Wang J, Liu Y. Results of phase III trial of rh-endostatin (YH-16) in adVanced non-small cell lung cancer (NSCLC) patients. J Clin Oncol 2005;23:abstract 7138.
67. Han B, Xiu Q, Wang H. Rh-endostatin Injection plus paclitaxel and carboplatin therapy for non-small-cell lung cancer: Randomized, double-blind, placebo-controlled, multicentre study. J Clin Oncol 2008;26:191126.
68. Massarelli E, Miller VA, Leighl NB. Phase II study of the efficacy and safety of intravenous (IV) AVE0005 (VEGF Trap) given every 2 weeks in patients (Pts) with platinum- and erlotinibresistant adenocarcinoma of the lung (NSCLA). J Clin Oncol 2007;18S:Abstract 7627.
69. A study of Aflibercept versus placebo in patients with secondline Docétaxel for locally adVanced or metastatic non-smallcell lung cancer. Available at: http://clinicaltrials.gov. Last updated 04/13/2009.
70. Rugo HS, Herbst RS, Liu G, et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with adVanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol 2005;23:5474-83.
71. 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;27:3836-41.
72. 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;65:4389-400.
73. Goss GD, Laurie S, Shepherd F. Phase I study of daily oral AZD2171, a vascular endothelial growth factor receptor inhibitor (VEGFRI), in combination with gemcitabine and cisplatin (G/C) in patients with adVanced non-small cell lung cancer (ANSCLC): a study of the NCIC Clinical Trials Group. J Clin Oncol 2007;25:abstract 7649.
74. Laurie SA, Gauthier I, Arnold A, et al. Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with adVanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group. J Clin Oncol 2008;26:1871-8.
75. Laurie SA, Arnold A, Shepherd FA. Overall survival [OS] results of NCIC Clinical Trials Group [CTG] BR.24: a randomized, double-blind trial of carboplatin + paclitaxel [C + P] with either daily oral cediranib, a potent inhibitor of all vascular endothelial growth factor receptor tyrosine kinases, or placebo, in adVanced non-small cell lung cancer [NSCLC]. J Thorac Oncol 2009;4:S353:abstract C1.1.
76. Rosen LS, Kurzrock R, Mulay M, et al. Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with adVanced solid tumors. J Clin Oncol 2007;25:2369-76.
77. Blumenschein G, Sandler A, O'Rourke T. Safety and pharmacokinetics (PK) of AMG 706 with carboplatin/paclitaxel (C/P) and/or panitumumab for the treatment of patients with adVanced non-small cell lung cancer (NSCLC). J Thorac Oncol 2007;2:S469.
78. Crawford J, Burris H, Stein M. Safety and pharmacokinetics (PK) of AMG 706, panitumumab, and gemcitabine/cisplatin (GC) for the treatment of adVanced solid malignancies. J Clin Onco 2006;24:Abtract 13005.
79. Study to evaluate AMG 706 with or without Carboplatin/ Paclitaxel or Panitumumab in the treatment of subjects with adVanced non-small cell lung cancer (NSCLC) (MONET). Available at: http://clinicaltrials.gov. Last updated 04/13/2009.
80. Blumenschein GR, Kabbinavar FF, Menon H, et al. Randomized, open-label phase II study of motesanib or bevacizumab in combination with paclitaxel and carboplatin (P/C) for adVanced nonsquamous non-small cell lung cancer (NSCLC). J Clin Oncol 2010;28:15s.(suppl; abstract 7528).
81. Nikolinakos P, Altorki N, Guarino MJ. Analyses of plasma cytokine/ angiogenic factors (C/AFs) profile during preoperative treatment with pazopanib (GW786034) in early-stage nonsmall cell lung cancer. J Clin Oncol 2008;26:abstract 7568.
82. Adnane L, Trail PA, Taylor I. Sorafénib (BAY 43-9006 Nexavar (R)), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol 2005;407:597-612.
83. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004;64:7099-109.
84. Escudier B, Eisen T, Stadler WM, et al. Sorafénib in adVanced clear-cell renal-cell carcinoma. N Engl J Med 2007;356:125-34.
85. Llovet J, Ricci S, Mazzaferro V. Sorafénib improves survival in adVanced hepatocellular carcinoma (HCC): results of a phase III randomized placebo-controlled trial (SHARP trial). J Clin Oncol 2007;25:abstract LBA1. 2007.
86. Adjei AA, Molina JR, Hillman SL. A front-line window of opportunity phase II study of sorafénib in patients with adVanced non-small cell lung cancer: a North Central Cancer Treatment Group study. J Clin Oncol 2007;25:abstract 7547.
87. Adjei AA, Molina JR, Mandrekar SJ, et al. Phase I trial of sorafénib in combination with gefitinib in patients with refractory or recurrent non-small cell lung cancer. Clin Cancer Res 2007;13:2684-91.
88. Gatzemeier U, Blumenschein G, Fossella F. Phase II trial of single-agent sorafénib in patients with adVanced non-small cell lung carcinoma. J Clin Oncol 2006;24:abstract 7002.
89. Gridelli C, Rossi A, Mongillo F, et al. A randomized phase II study of sorafénib/gemcitabine or sorafénib/erlotinib for adVanced non-small-cell lung cancer in elderly patients or patients with a performance status of 2: treatment rationale and protocol dynamics. Clin Lung Cancer 2007;8:396-8.
90. Gutierrez M, Kummar S, Allen DS. A phase II study of multikinase inhibitor sorafénib in patients with relapsed non-small cell lung cancer (NSCLC). J Clin Oncol 2008;26:abstract 19084.
91. Schiller JH, Lee JW, Hanna NH. A randomized discontinuation phase II study of sorafénib versus placebo in patients with non-small cell lung cancer who have failed at least two prior chemotherapy regimens: E2501. J Clin Oncol 2008;26:abstract 8014.
92. Dingemans AMC, Van Wijk A, Hochstenbag M. Sorafénib in pretreated patients with adVanced non-small lung cancer harbouring a K-ras mutation. J Thorac Oncol 2009;4:S414-5:abstract D106.
93. Scagliotti G, Novello S, von Pawel J, et al. Phase III study of carboplatin and paclitaxel alone or with sorafénib in adVanced non-small-cell lung cancer. J Clin Oncol 2010;28:1835-42.
94. Gatzemeier U, Eisen T, Santoro A, et al. Sorafénib (S) + gemcitabine/cisplatin (GC) VS GC alone in the firstline treatment of adVanced non-small cell lung cancer (NSCLC): Phase III NSCLC research experience utilizing sorafénib (NEXUS) trial. Ann Oncol 2010;21;viii1-2, LBA16.
95. Adjei AA, Mandrekar S, Marks RS. A Phase I study of BAY 43-9006 and gefitinib in patients with refractory or recurrent nonsmall- cell lung cancer (NSCLC). J Clin Oncol 2005;23:abstract 3067.
96. Spigel DR, Anthony Greco F, Burris III HA. A randomized double-blind placebo-controlled phase II trial of sorafénib and erlotinib or erlotinib alone in previously treated adVanced non-small-cell lung cancer. J Thorac Oncol 2009;4:S355:abstract D1.5.
97. Novello S, Scagliotti GV, Rosell R, et al. Phase II study of continuous daily sunitinib dosing in patients with previously treated adVanced non-small cell lung cancer. Br J Cancer 2009;101:1543-8.
98. Raymond E, Faivre S, Vera K. Final results of a phase I and pharmacokinetic study of SU11248, a novel multi-traget tyrosine kinase inhibitor, in patients with adVanced cancers. Proc Am Soc Clin Oncol 2003;22:abstract 769.
99. Socinski MA, Novello S, Brahmer JR, et al. Multicenter, phase II trial of sunitinib in previously treated, adVanced non-smallcell lung cancer. J Clin Oncol 2008;26:650-6.
100. Reck M, Frickhofen N, Cedres S, et al. Sunitinib in combination with gemcitabine plus cisplatin for adVanced non-small cell lung cancer: a phase I dose-escalation study. Lung Cancer 2010;70:180-7.
101. Socinski MA, Scappaticci FA, Samant M, et al. Safety and efficacy of combining sunitinib with bevacizumab + paclitaxel/carboplatin in non-small cell lung cancer. J Thorac Oncol 2010;5:354-60.
102. Scagliotti G, Krzakowski M, Szczesna A, et al. Sunitinib (SU) in combination with erlotinib (E) for the treatment of adVanced/ metastatic non-small cell lung cancer (NSCLC): A phase III study. Ann Oncol 2010;21;viii1-2, LBA6.
103. Ciardiello F, Caputo R, Damiano V, et al. Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase. Clin Cancer Res 2003;9:1546-56.
104. De Boer R, Humblet Y, Wolf J, et al. An open-label study of Vandetanib with pemetrexed in patients with previously treated non-small-cell lung cancer. Ann Oncol 2009;20: 486-91.
105. Heymach JV, Johnson BE, Prager D, et al. Randomized, placebo-controlled phase II study of Vandetanib plus docétaxel in previously treated non small-cell lung cancer. J Clin Oncol 2007;25:4270-7.
106. Holden SN, Eckhardt SG, Basser R, et al. Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors. Ann Oncol 2005;16:1391-7.
107. Natale RB, Bodkin D, Govindan R, et al. Vandetanib versus gefitinib in patients with adVanced non-small-cell lung cancer: results from a two-part, double-blind, randomized phase ii study. J Clin Oncol 2009;27:2523-9.
108. Herbst RS, Sun Y, Eberhardt WE, et al. Vandetanib plus docétaxel versus docétaxel as second-line treatment for patients with adVanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol 2010;11:619-26.
109. Harshman LC, Kuo CJ, Wong BY, et al. Increased hemoglobin associated with VEGF inhibitors in adVanced renal cell carcinoma. Cancer Invest 2009;27:851-6.
110. De Boer RH, Arrieta O, Yang CH, et al. Vandetanib plus pemetrexed for the second-line treatment of adVanced nonsmall- cell lung cancer: a randomized, double-blind phase III trial. J Clin Oncol 2011;29:1067-74.
111. Natale RB, Thongprasert S, Greco FA, et al. Phase III trial of Vandetanib compared with erlotinib in patients with previously treated adVanced non-small-cell lung cancer. J Clin Oncol 2011;29:1059-66.
112. Drvs J, Mross D, Medinger M. Phase I dose-escalation and pharmacokinetic (PK) study of the VEGF inhibitor PTK78/ZK 222584 (PTK/ZK) in patients with liver metastases. Proc Am Soc Clin Oncol 2003;22:abstract 1142.
113. Gauler TC, Besse B, Meric JB. Phase II open-label study to investigate efficacy and safety of PTK787/ZK 222584 (PTK/ZK) orally administered once daily or twice daily at 1,250 mg as second-line monotherapy in patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC). J Clin Oncol ASCO 2007;25:abstract 7541.
114. Morgan B, Horsfield MA, Stattaus J. Dynamic contrastenhanced magnetic resonance imaging (DCE-MRI) as a biomarker for the effect of PTK787/ZK 222584 (PTK/ZK) as second-line mono-therapy in patients with stage IIIB or stage IV non-small cell lung cancer (NSCLC). J Clin Oncol 2007;25:abstract 7676.
115. Camidge DR, Conkling P, Stephenson JJ, et al. Pharmacokinetic (PK) analysis of a phase I study of continuous oral treatment with the angiokinase inhibitor BIBF 1120, in combination with carboplatin and paclitaxel in patients with adVanced non-small cell lung cancer (NSCLC). J Clin Oncol 2008;26:abstract 3567.
116. Nikolinakos P, Heymach JV. The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies. J Thorac Oncol 2008;3:S131-4.
117. Zangari M, Fink LM, Elice F, et al. Thrombotic events in patients with cancer receiving antiangiogenesis agents. J Clin Oncol 2009;27:4865-73.
118. Siu LL, Awada A, Takimoto CH, et al. trial of sorafénib and gemcitabine in adVanced solid tumors with an expanded cohort in adVanced pancreatic cancer. Clin Cancer Res 2006;12:144-51.
119. Templeton A, Brandle M, Cerny T, et al. Remission of diabetes while on sunitinib treatment for renal cell carcinoma. Ann Oncol 2008;19:824-5.
120. Khakoo AY, Kassiotis CM, Tannir N, et al. Heart failure associated with sunitinib malate: a multitargeted receptor tyrosine kinase inhibitor. Cancer 2008;112:2500-8.
121. Patterson DM, Rustin GJ. Vascular damaging agents. Clin Oncol (R Coll Radiol) 2007;19:443-56.
122. Tozer GM, Kanthou C, Parkins CS, et al. The biology of the combretastatins as tumour vascular targeting agents. Int J Exp Pathol 2002;83:21-38.
123. McKeage MJ, Fong P, Jeffery M, et al. 5,6- Dimethylxanthenone-4-acetic acid in the treatment of refractory tumors: a phase I safety study of a vascular disrupting agent. Clin Cancer Res 2006;12:1776-84.
124. Ching LM, Goldsmith D, Joseph WR, et al. Induction of intratumoral tumor necrosis factor (TNF) synthesis and hemorrhagic necrosis by 5,6- dimethylxanthenone-4-acetic acid (DMXAA) in TNF knockout mice. Cancer Res 1999;59:3304-7.
125. Fukumura D, Jain RK. Role of nitric oxide in angiogenesis and microcirculation in tumors. Cancer Metastasis Rev 1998;17:77-89.
126. MahadeVan V, Malik ST, Meager A, et al. Role of tumor necrosis factor in flavone acetic acid-induced tumor vasculature shutdown. Cancer Res 1990;50:5537-42.
127. McKeage MJ, Reck M, Jameson MB, et al. Phase II study of ASA404 (vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA) 1800 mg/m(2) combined with carboplatin and paclitaxel in previously untreated adVanced non-small cell lung cancer. Lung Cancer 2009;65:192-7.
128. McKeage MJ, Von Pawel J, Reck M, et al. Randomised phase II study of ASA404 combined with carboplatin and paclitaxel in previously untreated adVanced non-small cell lung cancer. Br J Cancer 2008;99:2006-12.
129. Jameson MB, Thompson PI, Baguley BC, et al. Clinical aspects of a phase I trial of 5,6-dimethylxanthenone-4- acetic acid (DMXAA), a novel antivascular agent. Br J Cancer 2003;88:1844-50.
130. ASA404 or placebo in combination with paclitaxel and carboplatin as first-line treatment for stage IIIB/IV non-small cell lung cancer. Available at: http://clinicaltrials.gov. Last updated 04/13/2009.
131. A Study of ASA404 or placebo in combination with docétaxel in second-line treatment for (stage IIIB/IV) non-small cell lung cancer. Available at: http://clinicaltrials.gov. Last updated 04/13/2009.
132. Hida T, Takeda K, Daga H, et al. A safety and tolerability study of vadimezan in combination with docétaxel in Japanese patients with adVanced or recurrent solid tumors. J Clin Oncol 2010;28:abstract13106.
133. Kerr DJ, Kaye SB, Graham J, et al. Phase I and pharmacokinetic study of LM985 (flavone acetic acid ester). Cancer Res 1986;46:3142-6.
134. Dowlati A, Robertson K, Cooney M, et al. A phase I pharmacokinetic and translational study of the novel vascular targeting agent combretastatin a-4 phosphate on a single-dose intravenous schedule in patients with adVanced cancer. Cancer Res 2002;62:3408-16.
135. Rustin GJ, Galbraith SM, Anderson H, et al. Phase I clinical trial of weekly combretastatin A4 phosphate: clinical and pharmacokinetic results. J Clin Oncol 2003;21:2815-22.
136. Stevenson JP, Rosen M, Sun W, et al. Phase I trial of the antivascular agent combretastatin A4 phosphate on a 5-day schedule to patients with cancer: magnetic resonance imaging evidence for altered tumor blood flow. J Clin Oncol 2003;21:4428-38.
137. Gadgeel SM, LoRusso PM, Wozniak AJ. A dose-escalation study of the novel vascular targeting agent, ZD6126 in patients with solid tumors. Proc Am Soc Clin Oncol 2002;abstract 438.
138. Radema SA, Beerepoot LV, Wittevee PO. Clinical evaluation of the novel vascular-targeting agent, ZD6126: assessment of toxicity and surrogate markers of vascular damage. Proc Am Soc Clin Oncol 2002;abstract 439.
139. Dragnev KH, Rigas JR, Disalvo WM. A phase I trial of ABT- 751 and carboplatin (C) in patients (pts) with previously treated non-small cell lung cancer (NSCLC). J Clin Oncol 2006;abstract 17098.
140. Mauer AM, Cohen EE, Ma PC, et al. A phase II study of ABT- 751 in patients with adVanced non-small cell lung cancer. J Thorac Oncol 2008;3:631-6.
141. Lee SM, Rudd R, Woll PJ, et al. Randomized double-blind placebo-controlled trial of thalidomide in combination with gemcitabine and Carboplatin in adVanced non-small-cell lung cancer. J Clin Oncol 2009;27:5248-54.
142. Lee SM, Woll PJ, Rudd R, et al. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst 2009;101:1049-57.
143. 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;25:3945-51.
144. Otani M, Natsume T, Watanabe JI, et al. TZT-1027, an antimicrotubule agent, attacks tumor vasculature and induces tumor cell death. Jpn J Cancer Res 2000;91:837-44.