Targeting angiogenesis from multiple pathways simultaneously: BIBF 1120, an investigational novel triple angiokinase inhibitor

Investigational New Drugs

Volumn 30, Issue 3, 2012, Pages 1261-1269

  Santos, Edgardo S ^a   Gomez, Jorge E ^a   Raez, Luis E ^a  

^a UNIVERSITY OF MIAMI   (United States)

Author keywords

Antiangiogenesis; Bevacizumab; BIBF 1120; Sorafenib; Sunitinib; Vandetanib

Indexed keywords

BEVACIZUMAB; CARBOPLATIN; CISPLATIN; DOCETAXEL; ERLOTINIB; FLUOROPYRIMIDINE; GEMCITABINE; NINTEDANIB; PACLITAXEL; PEMETREXED; PLACEBO; PLATINUM COMPLEX; SORAFENIB; SUNITINIB; VANDETANIB;

ABDOMINAL PAIN; ADVANCED CANCER; ALOPECIA; ANOREXIA; BLEEDING; CANCER COMBINATION CHEMOTHERAPY; CANCER LOCALIZATION; CANCER SURVIVAL; CD4 LYMPHOCYTE COUNT; CHEMOTHERAPY INDUCED NAUSEA AND VOMITING; CLINICAL EFFECTIVENESS; COLON CANCER; COLORECTAL CANCER; COLORECTAL CARCINOMA; CONFUSION; DIARRHEA; DIZZINESS; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG ABSORPTION; DRUG APPROVAL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; ERYTHEMA; ESOPHAGUS PAIN; FATIGUE; FISTULA; GASTROINTESTINAL DISEASE; GASTROINTESTINAL STROMAL TUMOR; GLIOBLASTOMA; GYNECOLOGIC CANCER; HAND FOOT SYNDROME; HEADACHE; HUMAN; HYPERTENSION; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LOW DRUG DOSE; LUNG CANCER; LUNG NON SMALL CELL CANCER; MAXIMUM TOLERATED DOSE; METASTASIS; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MYALGIA; NAUSEA; NEUTROPENIA; OVARY CANCER; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEINURIA; REVIEW; SIDE EFFECT; SOLID TUMOR; THROMBOCYTOPENIA; THROMBOSIS; THYROID MEDULLARY CARCINOMA; TUMOR VASCULARIZATION; VOMITING;

ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL; HUMANS; INDOLES; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PROTEIN KINASE INHIBITORS;

EID: 84864345648     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-011-9644-2     Document Type: Review

References (59)

1. Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249-257
2. Weidner N (1998) Tumoural vascularity as a prognostic factor in cancer patients: the evidence continues to grow. J Pathol 184:119-122
3. Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581-611 (Pubitemid 39099316)
4. Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82:4-6 (Pubitemid 20020880)
5. Jain RK (2001) Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7:987-989 (Pubitemid 32937367)
6. Giaccone G (2007) The potential of antiangiogenic therapy in non-small cell lung cancer. Clin Cancer Res 13:1961-1970 (Pubitemid 46649861)
7. Clement-Duchene C, Wakelee H (2010) Antiangiogenic agents and vascular disrupting agents for the treatment of lung cancer: a review. J Thorac Oncol 5:129-139
8. McKeage MJ, Baguley BC (2010) Disrupting established tumor blood vessels: an emerging therapeutic strategy for cancer. Cancer 116:1859-1871
9. Jain RK, Booth MF (2003) What brings pericytes to tumor vessels? J Clin Invest 112:1134-1136 (Pubitemid 38056288)
10. Cao Y, Cao R, Hedlund EM (2008) Regulation of tumor angiogenesis and metastasis by FGF and PDGF signaling pathways. J Mol Med 86:785-789
11. Erber R, Thurnher A, Katsen AD, Groth G, Kerger H, Hammes HP, Menger MD, Ullrich A, Vajkoczy P (2004) Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J 18:338-340
12. Shih AH, Holland EC (2006) Platelet-derived growth factor (PDGF) and glial tumorigenesis. Cancer Lett 232:139-147 (Pubitemid 43170963)
13. Beenken A, Mohammadi M (2009) The FGF family: biology, pathophysiology and therapy Nat Rev Drug Discov 8:235-253
14. Presta M, DellEra P, Mitola S, Moroni E, Ronca R, Rusnati M (2005) Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 16:159-178 (Pubitemid 40616114)
15. Rosen LS (2002) Clinical experience with angiogenesis signaling inhibitors: focus on vascular endothelial growth factor (VEGF) blockers. Cancer Control 9:36-44 (Pubitemid 34457339)
16. Bergers G, Song S, Meyer-MorseN, BergslandE, Hanahan D (2003) Benefits oftargeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 111:1287-1295 (Pubitemid 36554699)
17. Casanovas O, Hicklin DJ, Bergers G, Hanahan D (2005) Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8:299-309 (Pubitemid 41443415)
18. Ferrara N, Hillan KJ, Gerber HP, Novotny W (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3:391-400 (Pubitemid 38618122)
19. Herbst RS (2006) Toxicities of antiangiogenic therapy in non-small-cell lung cancer. Clin Lung Cancer 8:S23-S30
20. Spigel DR, Hainsworth JD, Yardley DA, Raefsky E, Patton J, Peacock N, Farley C, Burris HA III, Greco FA (2010) Trache-oesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab. J Clin Oncol 28:43-48
21. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542-2550 (Pubitemid 44917502)
22. Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF III, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F (2004) Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 22:2184-2191 (Pubitemid 41095154)
23. Scagliotti G, Novello S, von Pawel J, Reck M, Pereira JR, Thomas M, Abrão Miziara JE, Balint B, de Marinis F, Keller A, Aren O, Csollak M, Albert I, Barrios CH, Grossi F, Krzakowski M, Cupit L, Cihon F, DiMatteo S, Hanna N (2010) Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol 28:1835-1842
24. Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C (2009) 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 27:1227-1234
25. Reck M, Von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C (2010) Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol 21:1804-1809
26. Miller VA, O'Conner P, Soh C, Kabbinavar F, for the ATLAS Investigators (2009) 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). J Clin Oncol 27:LBA8002
27. Penson RT, Dizon DS, Cannistra SA, Roche MR, Krasner CN, Berlin ST, Horowitz NS, Disilvestro PA, Matulonis UA, Lee H, King MA, Campos SM (2010) Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors. J Clin Oncol 28:154-159
28. Friedman HS, Prados MD, Wen PY, Mikkelsen T, SchiffD, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733-4740
29. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N, AVOREN Trial investigators (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103-2111 (Pubitemid 350296300)
30. O'Shaughnessy J, Miles D, Gray RJ, Dieras V, Perez EA, Zon R, Corte J, Zhou X, Phan S, Miller K (2010) A meta-analysis of overall survival data from three randomized trials of bevacizumab (BV) and first-line chemotherapy as treatment for patients with metastatic breast cancer (MBC). J Clin Oncol 28(15S):115s, Abstract 1005
31. Miles DW, Chan A, Romieu G, Dirix LY, Cortés J, Pivot X, Tomczak P, Juozaityte E, Harbeck N, Steger GG, The BO17708 Study Group (2010) Final Overall Survival (OS) Results from the Randomised, Double-Blind, Placebo-Controlled, Phase III AVADO Study of Bevacizumab (BV) Plus Docetaxel (D) Compared with Placebo (PL) Plus D for the First-Line Treatment of Locally Recurrent (LR) or Metastatic Breast Cancer (mBC). Presented at: San Antonio Breast Cancer Symposium, San Antonio, TX, USA, December 8-12
32. Genentech press release. Genentech Provides Update on Avastin for Metastatic Breast Cancer Following Reviews in Europe and the United States. http://www.gene.com/gene/news/press-releases/displaydo?method=detail&id= 13127. Accessed 3 February 2011
33. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA (2004) 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 64:7099-7109 (Pubitemid 39331023)
34. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, Negrier S, Chevreau C, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Anderson S, Hofilena G, Shan M, Pena C, Lathia C, Bukowski RM (2009) Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol 27:3312-3318
35. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378-390
36. Scagliotti G, von Pawel J, Reck M et al (2008) Sorafenib plus carboplatin/paclitaxel in chemonaive patients with stage IIIB-IV non-small cell lung cancer (NSCLC): interim analysis (IA) results from the phase III, randomized, double-blind, placebo-controlled, ESCAPE (Evaluation of Sorafenib, Carboplatin, and Paclitaxel Efficacy in NSCLC) trial. J Thorac Oncol 3:S97-S98, Abstract 2750
37. Bayer (2010) Press release. Phase III trial of Nexavar® in first-line advanced non-small cell lung cancer does not meet primary endpoint of overall survival. June 14, 2010. http://www.press. bayer.com/baynews/baynews.nsf/id/ EC452AB645C9D5BF C1257742001E3E13?Open&ccm=001. Accessed 27 August 2010
38. Heng DY, Kollmannsberger C (2010) Sunitinib. Recent Results CancerRes 184:71-82 (2010) SUTENT® (sunitinib malate) capsules, oral package insert. Pfizer Inc, New York, NY
39. Socinski MA, Novello S, Brahmer JR, Rosell R, Sanchez JM, Belani CP, Govindan R, Atkins JN, Gillenwater HH, Pallares C, Tye L, Selaru P, Chao RC, Scagliotti GV (2008) Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. J Clin Oncol 26:650-656 (Pubitemid 351264362)
40. Novello S, Scagliotti GV, Rosell R, Socinski MA, Brahmer J, Atkins J, Pallares C, Burgess R, Tye L, Selaru P, Wang E, Chao R, Govindan R (2009) Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer. Br J Cancer 101:1543-1548
41. Mitsudomi T (2010) Advances in target therapy for lung cancer. Jpn J Clin Oncol 40:101-106
42. AstraZeneca Oncology (2009) Vandetanib (Zactima™) Media Fact Sheet. http://multivu.prnewswire.com/mnr/astrazeneca/38570/docs/38570- vadetanib(zactima).pdf. Accessed 8 September 2010
43. Wells SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Vasselli J, Read J, Schlumberger M (2010) Vandetanib (VAN) in locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial (ZETA). Presented at the 14th International Thyroid Conference; September 11-16, 2010; Paris, France Abstract OC-021
44. Natale RB, Thongprasert S, Greco FA, Thomas M, Tsai CM, Sunpaweravong P, Ferry D, Langmuir P, Rowbottom JA, Goss GD (2009) Vandetanib versus erlotinib in patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one prior cytotoxic chemotherapy: a randomized, double-blind phase III trial (ZEST). J Clin Oncol 27:409s, Abstract 8009
45. De Boer R, Arrieta O, Gottfried M et al (2009) Vandetanib plus pemetrexed versus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer (NSCLC): a randomized, double-blind phase III trial (ZEAL). J Clin Oncol 27:409s, Abstract 8010
46. Herbst RS, Sun Y, Eberhardt WE, Germonpre P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE (2010) 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 11:619-626
47. Lee J, Hirsh V Park K, Qin S, Blajman CR, Perng R, Emerson L, Langmuir PB, Manegold C (2010) Vandetanib versus placebo in patients with advanced non-small cell lung cancer (NSCLC) after prior therapy with an EGFR tyrosine kinase inhibitor (TKI): a randomized, double-blind phase III trial (ZEPHYR). J Clin Oncol 28:7525
48. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ (2008) BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res 68:4774-4782
49. Roth GJ, Heckel A, Colbatzky F, Handschuh S, Kley J, Lehmann-Lintz T, Lotz R, Tontsch-Grunt U, Walter R, Hilberg F (2009) Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120). J Med Chem 52:4466-4480
50. Mross K, Stefanic M, Gmehling D, Frost A, Baas F, Unger C, Strecker R, Henning J, Gaschler-Markefski B, Stopfer P, de Rossi L, Kaiser R (2010) Phase I study of the angiogenesis inhibitor BIBF 1120in patients with advanced solid tumors. Clin Cancer Res 16:311-319
51. Okamoto I, Kaneda H, Satoh T, Okamoto W, Miyazaki M, Morinaga R, Ueda S, Terashima M, Tsuya A, Sarashina A, Konishi K, Arao T, Nishio K, Kaiser R, Nakagawa K (2010) Phase I safety, pharmacokinetic, and biomarker study of BIBF 1120, an oral triple tyrosine kinase inhibitor in patients with advanced solid tumors. Mol Cancer Ther Epub ahead of print
52. Ellis PM, Kaiser R, Zhao Y, Stopfer P, Gyorffy S, Hanna N (2010) Phase I open-label study of continuous treatment with BIBF 1120, a triple angiokinase inhibitor, and pemetrexed in pretreated non-small cell lung cancer patients. Clin Cancer Res 16:2881-2889
53. Von Pawel J, Kaiser R, Eschbach C, Love J, Staab A, Freiwald M, Bruno R, Stopfer P (2008) Efficacy, safety and pharmacokinetic (PK) results of a phase II study with the triple angiokinase inhibitor BIBF 1120 in patients suffering from advanced non small cell lung cancer (NSCLC). J Thorac Oncol 3:S61, Abstract 163O
54. Kropff M, Kienast J, Bisping G, Berdel WE, Gaschler-Markefski B, Stopfer P, Stefanic M, Munzert G (2009) An open-label dose-escalation study of BIBF 1120 in patients with relapsed or refractory multiple myeloma. Anticancer Res 29:4233-4238
55. Burger RA, Brady MF, Bookman MA, Walker JL, Homesley HD, Fowler J, Monk BJ, Greer BE, Boente M, Liang SX (2010) Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): a Gynecologic Oncology Group study. Oral presentation at: the 46th Annual Meeting of the American Society of Clinical Oncology; June 4-8; Chicago, IL, USA
56. Ledermann JA, Rustin GJ, Hackshaw A, Kaye SB, Jayson G, Gabra H, James LE, Bell S, Temple G, on behalf of NCRI Gynaecological Cancer Group (2009) A randomised phase II placebo-controlled trial using maintenance therapy to evaluate the vascular targeting agent BIBF 1120 following treatment of relapsed ovarian cancer. Presented at the 16th Biennial International Meeting of the European Society of Gynaecological Oncology; October 11-14; Belgrade, Serbia
57. Stopfer P, Droz JP, Fléchon A, Joly F, de Mont-Serrat H, Kaiser R, Oudard S (2009) Pharmacokinetic analysis of two dosing schedules of the angiokinase inhibitor BIBF 1120 in patients with hormone-refractory prostate cancer who progressed after docetaxel treatment. Eur J Cancer Suppl 7:419, Abstract 7044
58. Bergers G, Hanahan D (2008) Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8:592-603
59. Du Bois A, Huober J, Stopfer P, Pfisterer J, Wimberger P, Loibl S, Reichardt VL, Harter P (2010) A phase I open-label dose-escalation study of oral BIBF 1120 combined with standard paclitaxel and carboplatin in patients with advanced gynecological malignancies. Ann Oncol 21:370-375