An open-label dose-escalation study of BIBF 1120 in patients with relapsed or refractory multiple myeloma

Anticancer Research

Volumn 29, Issue 10, 2009, Pages 4233-4238

  Kropff, Martin ^a   Kienast, Joachim ^a   Bisping, Guido ^a   Berdel, Wolfgang E ^a   Gaschler Markefski, Birgit ^b   Stopfer, Peter ^b   Stefanic, Martin ^b   Munzert, Gerd ^b  

^a UNIVERSITY OF MÜNSTER   (Germany)

^b BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

BIBF 1120; Multiple myeloma; Pharmacokinetics; Phase I study; VEGF receptor inhibitor

Indexed keywords

ANTHRACYCLINE; BIBF 1120; DEXAMETHASONE; GAMMA GLUTAMYLTRANSFERASE;

ABDOMINAL PAIN; ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DISEASE SEVERITY; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; FATIGUE; FEMALE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; GASTROINTESTINAL DISEASE; HUMAN; IMMUNOTHERAPY; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MULTIPLE MYELOMA; NAUSEA; OPEN STUDY; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RELAPSE; SIDE EFFECT; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT OUTCOME; TREATMENT RESPONSE; VOMITING;

ADMINISTRATION, ORAL; ANTINEOPLASTIC AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; INDOLES; MALE; MULTIPLE MYELOMA;

EID: 71949096844     PISSN: 02507005     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (20)

1. Herbst RS: Therapeutic options to target angiogenesis in human malignancies. Expert Opin Emerg Drugs 11: 635-650, 2006. (Pubitemid 44735590)
2. Rajkumar SV, Mesa RA, Fonseca R, Schroeder G, Plevak MF, Dispenzieri A, Lacy MQ, Lust JA, Witzig TE, Gertz MA, Kyle RA, Russell SJ and Greipp PR: Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res 8: 2210-2216, 2002. (Pubitemid 34753592)
3. Moehler TM, Neben K, Ho AD and Goldschmidt H: Angiogenesis in hematologic malignancies. Ann Hematol 80: 695-705, 2001.
4. Pruneri G, Ponzoni M, Ferreri AJ, Decarli N, Tresoldi M, Raggi F, Baldessari C, Freschi M, Baldini L, Goldaniga M, Neri A, Carboni N, Bertolini F and Viale G: Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients. Br J Haematol 118: 817-820, 2002. (Pubitemid 35007388)
5. Lin B, Podar K, Gupta D, Tai YT, Li S, Weller E, Hideshima T, Lentzsch S, Davies F, Li C, Weisberg E, Schlossman RL, Richardson PG, Griffin JD, Wood J, Munshi NC and Anderson KC: The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment. Cancer Res 62: 5019-5026, 2002. (Pubitemid 34984429)
6. Dankbar B, Padro T, Leo R, Feldmann B, Kropff M, Mesters RM, Serve H, Berdel WE and Kienast J: Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood 95: 2630-2636, 2000. (Pubitemid 30210543)
7. Podar K, Tai YT, Davies FE, Lentzsch S, Sattler M, Hideshima T, Lin BK, Gupta D, Shima Y, Chauhan D, Mitsiades C, Raje N, Richardson P and Anderson KC: Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood 98: 428-435, 2001.
8. Dalton WS, Bergsagel PL, Kuehl WM, Anderson KC and Harousseau JL: Multiple myeloma. Hematology Am Soc Hematol Educ Program pp. 157-177, 2001.
9. Bisping G, Kropff M, Wenning D, Dreyer B, Bessonov S, Hilberg F, Roth GJ, Munzert G, Stefanic M, Stelljes M, Scheffold C, Muller-Tidow C, Liebisch P, Lang N, Tchinda J, Serve HL, Mesters RM, Berdel WE and Kienast J: Targeting receptor kinases by a novel indolinone derivative in multiple myeloma: abrogation of stroma-derived interleukin-6 secretion and induction of apoptosis in cytogenetically defined subgroups. Blood 107: 2079-2089, 2006. (Pubitemid 43289392)
10. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A and Rettig W: BIBF1120: Triple angiokinase inhibitor with sustained receptor blockade and good anti-tumor efficacy Cancer Research 68: 4774-4782, 2008.
11. Hilberg F, Tontsch-Grunt U, Heckel A, Colbatzky F, v Meel JCA, Lotz R and Roth GJ. BIBF1120 a novel, small molecule triple angiokinase inhibitor: profiling as a clinical candidate for cancer therapy. In: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2004 28 September - 1 October; Geneva, Switzerland, 2004.
12. Krssák M, Kriz M, Stefanie M and Hilberg F: BIBF 1120, a small molecule triple angiokinase inhibitor, affects the tumor vasculature in human tumor xenografts on nude mice as detected by DCE-MRI. Proc AACR-NCI-EORTC Int Conf Mol Targets and Cancer Thera 60(A22): 2005.
13. Mross KB, Gmehling D, Frost A, Baas F, Strecker R, Hennig J, Stopfer P, Stefanic M, Stehle G and de Rossi L: A clinical phase I, pharmacokinetic (PK), and pharmacodynamic study of twice-daily BIBF 1120 in advanced cancer patients. J Clin Oncol 23: 3031, 2005.
14. Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S and Vesole D: Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 102: 1115-1123, 1998.
15. Lee CP, Taylor NJ, Attard G, Nathan PD, de Bono JS, Temple GM, Tang A, Padhani AR, Judson IR and Rustin GJ: A phase I study of BIBF 1120, an orally active triple angiokinase inhibitor (VEGFR, PDGFR, FGFR) given continuously to patients with advanced solid tumours, incorporating dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). J Clin Oncol 24: 3015, 2006.
16. Ratain MJ, Eisen T, Stadler WM, Flaherty KT, Kaye SB, Rosner GL, Gore M, Desai AA, Patnaik A, Xiong HQ, Rowinsky E, Abbruzzese JL, Xia C, Simantov R, Schwartz B and O'Dwyer PJ: Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 24: 2505-2512, 2006. (Pubitemid 46630627)
17. Kovacs MJ, Reece DE, Marcellus D, Meyer RM, Mathews S, Dong RP and Eisenhauer E: A phase II study of ZD6474 (Zactima), a selective inhibitor of VEGFR and EGFR tyrosine kinase, in patients with relapsed multiple myeloma-NCIC CTG IND.145. Invest New Drugs 24: 529-535, 2006. (Pubitemid 44273029)
18. Zangari M, Anaissie E, Stopeck A, Morimoto A, Tan N, Lancet J, Cooper M, Hannah A, Garcia-Manero G, Faderl S, Kantarjian H, Cherrington J, Albitar M and Giles FJ: Phase II study of SU5416, a small molecule vascular endothelial growth factor tyrosine kinase receptor inhibitor, in patients with refractory multiple myeloma. Clin Cancer Res 10: 88-95, 2004. (Pubitemid 38114166)
19. Bisping G, Wenning D, Kropff MH, Munzert G, Hilberg F, Roth GJ, Berdel WE and Kienast J: Enhanced anti-myeloma activity by combination of receptor tyrosine kinase (RTK) inhibition, proteasome inhibition, and dexamethasone: therapeutic implications for t(4;14) and t(14;16) multiple myeloma (MM) subgroups. ASH Annual Meeting Abstracts 106: Abstract 112, 2005.
20. Podar K, Tonon G, Sattler M, Tai YT, Legouill S, Yasui H, Ishitsuka K, Kumar S, Kumar R, Pandite LN, Hideshima T, Chauhan D and Anderson KC: The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. Proc Natl Acad Sci USA 103: 19478-19483, 2006. (Pubitemid 46026056)