A randomized phase II study of cilengitide (EMD 121974) in patients with metastatic melanoma

Melanoma Research

Volumn 22, Issue 4, 2012, Pages 294-301

  Kim, Kevin B ^a   Prieto, Victor ^a   Joseph, Richard W ^a   Diwan, Abdul H ^a   Gallick, Gary E ^a   Papadopoulos, Nicholas E ^a   Bedikian, Agop Y ^a   Camacho, Luis H ^a   Hwu, Patrick ^a   Ng, Chaan S ^a   Wei, Wei ^a   Johnson, Marcella M ^a   Wittemer, Sabine M ^c   Vardeleon, Anna ^a   Reckeweg, Aaron ^a   Colevas, A Dimitrios ^b  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c MERCK KGAA   (Germany)

Author keywords

v 3; cilengitide; integrin; melanoma; phase II

Indexed keywords

CILENGITIDE;

ADULT; ANEMIA; ANOREXIA; ARTHRALGIA; ARTICLE; BONE METASTASIS; BRAIN METASTASIS; CANCER CHEMOTHERAPY; CHILD; CLINICAL ARTICLE; COMPUTER ASSISTED TOMOGRAPHY; CONTROLLED STUDY; COUGHING; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFICACY; DYSPNEA; EDEMA; ERYTHEMA; EYE TOXICITY; FATIGUE; FEMALE; FEVER; GASTROINTESTINAL DISEASE; HUMAN; KAPLAN MEIER METHOD; LIQUID CHROMATOGRAPHY; LIVER METASTASIS; LUNG METASTASIS; LYMPH NODE METASTASIS; LYMPHOCYTOPENIA; MALE; MASS SPECTROMETRY; MELANOMA; METASTASIS; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; THROMBOCYTOPENIA; TREATMENT RESPONSE; VOMITING;

ADULT; AGED; AGED, 80 AND OVER; DISEASE-FREE SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MELANOMA; MIDDLE AGED; NEOPLASM METASTASIS; SKIN NEOPLASMS; SNAKE VENOMS;

EID: 84863721411     PISSN: 09608931     EISSN: 14735636     Source Type: Journal    
DOI: 10.1097/CMR.0b013e32835312e4     Document Type: Article

References (27)

1. Hynes RO. Integrins: a family of cell surface receptors. Cell 1987; 48: 549-554.
2. Varner JA, Cheresh DA. Integrins and cancer. Curr Opin Cell Biol 1996; 8:724-730.
3. Davis GE. Affinity of integrins for damaged extracellular matrix: alpha v beta 3 binds to denatured collagen type I through RGD sites. Biochem Biophys Res Commun 1992; 182:1025-1031.
4. Brooks PC, Stromblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WG, et al. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell 1996; 85:683-693.
5. Stromblad S, Becker JC, Yebra M, Brooks PC, Cheresh DA. Suppression of p53 activity and p21WAF1/CIP1 expression by vascular cell integrin alphaVbeta3 during angiogenesis. J Clin Invest 1996; 98:426-433.
6. Wu C, Keivens VM, O'Toole TE, McDonald JA, Ginsberg MH. Integrin activation and cytoskeletal interaction are essential for the assembly of a fibronectin matrix. Cell 1995; 83:715-724.
7. Gao AG, Lindberg FP, Dimitry JM, Brown EJ, Frazier WA. Thrombospondin modulates alpha v beta 3 function through integrin-associated protein. J Cell Biol 1996; 135:533-544.
8. Eliceiri BP, Cheresh DA. The role of alphav integrins during angiogenesis: insights into potential mechanisms of action and clinical development. J Clin Invest 1999; 103:1227-1230.
9. Van Belle PA, Elenitsas R, Satyamoorthy K,Wolfe JT, Dt Guerry, Schuchter L, et al. Progression-related expression of beta3 integrin in melanomas and nevi. Hum Pathol 1999; 30:562-567.
10. Kageshita T, Hamby CV, Hirai S, Kimura T, Ono T, Ferrone S. Differential clinical significance of alpha(v)Beta(3) expression in primary lesions of acral lentiginous melanoma and of other melanoma histotypes. Int J Cancer 2000; 89:153-159.
11. Natali PG, Hamby CV, Felding-Habermann B, Liang B, Nicotra MR, Di Filippo F, et al. Clinical significance of alpha(v)beta3 integrin and intercellular adhesion molecule-1 expression in cutaneous malignant melanoma lesions. Cancer Res 1997; 57:1554-1560.
12. Dechantsreiter MA, Planker E, Matha B, Lohof E, Holzemann G, Jonczyk A, et al. N-methylated cyclic RGD peptides as highly active and selective alpha(V)beta(3) integrin antagonists. J Med Chem 1999; 42: 3033-3040.
13. Eskens FA, Dumez H, Hoekstra R, Perschl A, Brindley C, Bottcher S, et al. Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours. Eur J Cancer 2003; 39:917-926.
14. Nabors LB, Mikkelsen T, Rosenfeld SS, Hochberg F, Akella NS, Fisher JD, et al. Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. J Clin Oncol 2007; 25:1651-1657.
15. Bedikian AY, Millward M, Pehamberger H, Conry R, Gore M, Trefzer U, et al. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol 2006; 24:4738-4745.
16. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics 1975; 31: 103-115.
17. Therasse P, Arbuck SG, Eisenhauer EA,Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000; 92:205-216.
18. Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989; 10:1-10.
19. Reardon DA, Fink KL, Mikkelsen T, Cloughesy TF, O'Neill A, Plotkin S, et al. Randomized phase II study of cilengitide, an integrin-targeting arginineglycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol 2008; 26:5610-5617.
20. Hersey P, Sosman J, O'Day S, Richards J, Bedikian A, Gonzalez R, et al. A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin alpha(v)beta(3), +/-dacarbazine in patients with stage IV metastatic melanoma. Cancer 2010; 116:1526-1534.
21. Kim S, Bell K, Mousa SA, Varner JA. Regulation of angiogenesis in vivo by ligation of integrin alpha5beta1 with the central cell-binding domain of fibronectin. Am J Pathol 2000; 156:1345-1362.
22. Beauvais A, Erickson CA, Goins T, Craig SE, Humphries MJ, Thiery JP, et al. Changes in the fibronectin-specific integrin expression pattern modify the migratory behavior of sarcoma S180 cells in vitro and in the embryonic environment. J Cell Biol 1995; 128:699-713.
23. Qian F, Zhang ZC,Wu XF, Li YP, Xu Q. Interaction between integrin alpha(5) and fibronectin is required for metastasis of B16F10 melanoma cells. Biochem Biophys Res Commun 2005; 333:1269-1275.
24. Fruehauf JP, Lutzky J, McDermott DF, Brown CK, Meric JB, Rosbrook B, et al. Multicenter, phase II study of axitinib, a selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, in patients with metastatic melanoma. Clin Cancer Res 2011; 17: 7642-7469.
25. Boss DS, Glen H, Beijnen JH, Keesen M, Morrison R, Tait B, et al. A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours. Br J Cancer 2012. doi: 10.1038/bjc.2012.154. [Epub ahead of print].
26. Tentori L, Dorio AS, Muzi A, Lacal PM, Ruffini F, Navarra P, et al. The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma. Oncol Rep 2008; 19: 1039-1043.
27. Stupp R, Hegi ME, Neyns B, Goldbrunner R, Schlegel U, Clement PM, et al. Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol 2010; 28:2712-2718.