Phase II Study of SU5416, a Small Molecule Vascular Endothelial Growth Factor Tyrosine Kinase Receptor Inhibitor, in Patients with Refractory Multiple Myeloma

Clinical Cancer Research

Volumn 10, Issue 1 I, 2004, Pages 88-95

  Zangari, Maurizio ^a   Anaissie, Elias ^a   Stopeck, Alison ^b   Morimoto, Alyssa ^c   Tan, Nguyen ^c   Lancet, Jeffrey ^d   Cooper, Maureen ^e   Hannah, Alison ^c   Garcia Manero, Guillermo ^f   Faderl, Stephan ^f   Kantarjian, Hagop ^f   Cherrington, Julie ^c   Albitar, Maher ^f   Giles, Francis J ^f  

^a UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

^b UNIVERSITY OF ARIZONA   (United States)

^c SUGEN INC   (United States)

^d UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^e Indianapolis Community Cancer Center   (United States)

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

Author keywords

[No Author keywords available]

Indexed keywords

ANTIHISTAMINIC AGENT; CORTICOSTEROID; CYTOTOXIC AGENT; DEXAMETHASONE; DIPHENHYDRAMINE; DOXORUBICIN; FAMOTIDINE; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; SEMAXANIB; THALIDOMIDE; VASCULOTROPIN; VASCULOTROPIN INHIBITOR; VASCULOTROPIN RECEPTOR 2; VINCRISTINE;

ADULT; ADVANCED CANCER; AGED; ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; ARTICLE; BACTEREMIA; BLOOD SAMPLING; BONE MARROW SUPPRESSION; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER SURVIVAL; CLINICAL ARTICLE; CLINICAL PROTOCOL; CLINICAL TRIAL; DIARRHEA; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; FATIGUE; FEMALE; GASTROINTESTINAL SYMPTOM; HEADACHE; HUMAN; HYPERTENSION; LUNG EMBOLISM; MALE; MULTICENTER STUDY; MULTIPLE MYELOMA; NAUSEA; NEUTROPENIA; OUTCOMES RESEARCH; PHASE 2 CLINICAL TRIAL; PHLEBITIS; PNEUMONIA; PRIORITY JOURNAL; PROGNOSIS; PROTEIN BLOOD LEVEL; REGULATORY MECHANISM; SURVIVAL RATE; THROMBOCYTOPENIA; THROMBOEMBOLISM; THROMBOSIS; TREATMENT FAILURE; VOMITING;

ADULT; AGED; ANGIOGENESIS INHIBITORS; DRUG RESISTANCE, NEOPLASM; ENZYME INHIBITORS; FEMALE; HUMANS; INDOLES; MALE; MIDDLE AGED; MULTIPLE MYELOMA; NEOVASCULARIZATION, PATHOLOGIC; PROTEIN-TYROSINE KINASES; PYRROLES; REMISSION INDUCTION; SALVAGE THERAPY; SURVIVAL RATE; THALIDOMIDE; TUMOR MARKERS, BIOLOGICAL; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 1642453748     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-0221-3     Document Type: Article

References (69)

1. Vacca, A., Ribatti, D., Roncali, L., Ranieri, G., Serio, G., Silvestris, F., and Dammacco, F. Bone marrow angiogenesis and progression in multiple myeloma. Br. J. Haematol., 87: 503-508, 1994.
2. Salven, P. Angiogenesis in lymphoproliferative disorders. Acta Haematol., 106: 184-189, 2001.
3. Folkman, J. Angiogenesis-dependent diseases. Semin. Oncol., 28: 536-542, 2001.
4. Xu, J. L., Lai, R., Kinoshita, T., Nakashima, N., and Nagasaka, T. Proliferation, apoptosis, and intratumoral vascularity in multiple myeloma: correlation with the clinical stage and cytological grade. J. Clin. Pathol., 55: 530-534, 2002.
5. Laroche, M., Brousset, P., Ludot, I., Mazieres, B., Thiechart, M., and Attal, M. Increased vascularization in myeloma. Eur. J. Haematol., 66: 89-93, 2001.
6. Rajkumar, S. V., Leong, T., Roche, P. C., Fonseca, R., Dispenzieri, A., Lacy, M. Q., Lust, J. A., Witzig, T. E., Kyle, R. A., Gertz, M. A., and Greipp, P. R. Prognostic value of bone marrow angiogenesis in multiple myeloma. Clin. Cancer Res., 6: 3111-3116, 2000.
7. Rajkumar, S. V., and Kyle, R. A. Angiogenesis in multiple myeloma. Semin. Oncol., 28: 560-564, 2001.
8. Rajkumar, S. V., Mesa, R. A., Fonseca, R., Schroeder, G., Plevak, M. F., Dispenzieri, A., Lacy, M. Q., Lust, J. A., Witzig, T. E., Gertz, M. A., Kyle, R. A., Russell, S. J., and Greipp, P. R. Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin. Cancer Res., 8: 2210-2216, 2002.
9. Moehler, T. M., Neben, K., Ho, A. D., and Goldschmidt, H. Angiogenesis in hematologic malignancies. Ann. Hematol., 80: 695-705, 2001.
10. Pruneri, G., Ponzoni, M., Ferreri, A. J., 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.
11. Rajkumar, S. V., and Witzig, T. E. A review of angiogenesis and antiangiogenic therapy with thalidomide in multiple myeloma. Cancer Treat. Rev., 26: 351-362, 2000.
12. Zachary, I., and Gliki, G. Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc. Res., 49: 568-581, 2001.
13. Benjamin, L. E., and Keshet, E. Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF VEOF withdrawal. Proc. Natl. Acad. Sci. USA, 94: 8761-8766, 1997.
14. Verstovsek, S., Estey, E., Manshouri, T., Giles, F. J., Cortes, J., Beran, M., Rogers, A., Keating, M., Kantarjian, H., and Albitar, M. Clinical relevance of vascular endothelial growth factor receptors 1 and 2 in acute myeloid leukaemia and myelodysplastic syndrome. Br. J. Haematol., 118: 151-156, 2002.
15. Clauss, M. Molecular biology of the VEGF and the VEGF receptor family. Semin. Thromb. Hemostasis, 26: 561-569, 2000.
16. Di Raimondo, F., Azzaro, M. P., Palumbo, G., Bagnato, S., Giustolisi, G., Floridia, P., Sortino, G., and Giustolisi, R. Angiogenic factors in multiple myeloma: higher levels in bone marrow than in peripheral blood. Haematologica, 85: 800-805, 2000.
17. Sezer, O., Jakob, C., Eucker, J., Niemoller, K., Gatz, F., Wernecke, K., and Possinger, K. Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in multiple myeloma. Eur. J. Haematol., 66: 83-88, 2001.
18. Paydas, S., Zorludemir, S., Baslamisli, F., and Tuncer, I. Vascular endothelial growth factor (VEGF) expression in plasmacytoma. Leuk. Lymphoma, 43: 139-143, 2002.
19. Giles, F. J. The vascular endothelial growth factor (VEGF) signaling pathway: a therapeutic target in patients with hematologic malignancies. Oncologist, 6: 32-39, 2001.
20. Smolich, B. D., Yuen, H. A., West, K. A., Giles, F. J., Albitar, M., and Cherrington, J. M. The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood, 97: 1413-1421, 2001.
21. Bellamy, W. T. Expression of vascular endothelial growth factor and its receptors in multiple myeloma and other hematopoietic malignancies. Semin. Oncol., 28: 551-559, 2001.
22. Lin, B., Podar, K., Gupta, D., Tai, Y. T., Li, S., Weller, E., Hideshima, T., Lentzsch, S., Davies, F., Li, C., Weisberg, E., Schlossman, R. L., Richardson, P. G., Griffin, J. D., Wood, J., Munshi, N. C., and Anderson, K. C. 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.
23. Podar, K., Tai, Y. T., Davies, F. E., Lentzsch, S., Sattler, M., Hideshima, T., Lin, B. K., Gupta, D., Shima, Y., Chauhan, D., Mitsiades, C., Raje, N., Richardson, P., and Anderson, K. C. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood, 98: 428-435, 2001.
24. Dankbar, B., Padro, T., Leo, R., Feldmann, B., Kropff, M., Mesters, R. M., Serve, H., Berdel, W. E., and Kienast, J. Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood, 95: 2630-2636, 2000.
25. Mendel, D. B., Schreck, R. E., West, D. C., Li, G., Strawn, L. M., Tanciongco, S. S., Vasile, S., Shawver, L. K., and Cherrington, J. M. The angiogenesis inhibitor SU5416 has long-lasting effects on vascular endothelial growth factor receptor phosphorylation and function. Clin. Cancer Res., 6: 4848-4858, 2000.
26. Sukbuntherng, J., Cropp, G., Hannah, A., Wagner, G. S., Shawver, L.K., and Antonian, L. Pharmacokinetics and interspecies scaling of a novel VEGF receptor inhibitor, SU54162. J. Pharm. Pharmacol., 53: 1629-636, 2001.
27. Fong, T. A., Shawver, L. K., Sun, L., Tang, C., App, H., Powell, T. J., Kim, Y. H., Schreck, R., Wang, X., Risau, W., Ullrich, A., Hirth, K. P., and McMahon, G. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res., 59: 99-106, 1999.
28. Vajkoczy, P., Menger, M. D., Vollmar, B., Schilling, L., Schmiedek, P., Hirth, K. P., Ullrich, A., and Fong, T. A. Inhibition of tumor growth, angiogenesis, and microcirculation by the novel Flk-1 inhibitor SU5416 as assessed by intravital multi-fluorescence videomicroscopy. Neoplasia, 1: 31-41, 1999.
29. Shaheen, R. M., Davis, D. W., Liu, W., Zebrowski, B. K., Wilson, M. R., Bucana, C. D., McConkey, D. J., McMahon, G., and Ellis, L. M. Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis. Cancer Res., 59: 5412-5416, 1999.
30. Mendel, D. B., Laird, A. D., Smolich, B. D., Blake, R. A., Liang, C., Hannah, A. L., Shaheen, R. M., Ellis, L. M., Weitman, S., Shawver, L. K., and Cherrington, J. M. Development of SU5416, a selective small molecule inhibitor of VEGF receptor tyrosine kinase activity, as an anti-angiogenesis agent. Anticancer Drug Des., 15: 29-41, 2000.
31. Kuenen, B. C., Rosen, L., Smit, E. F., Parson, M. R., Levi, M., Ruijter, R., Huisman, H., Kedde, M. A., Noordhuis, P., van der Vijgh, W. J., Peters, G. J., Cropp, G. F., Scigalla, P., Hoekman, K., Pinedo, H. M., and Giaccone, G. Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors. J. Clin. Oncol., 20: 1657-1667, 2002.
32. List, A. F. Vascular endothelial growth factor signaling pathway as an emerging target in hematologic malignancies. Oncologist, 6: 24-31, 2001.
33. Giles, F. J. The emerging role of angiogenesis inhibitors in hematologic malignancies. Oncology (Huntingt)., 16 (Suppl 4): 23-29, 2002.
34. Hideshima, T., Chauhan, D., Podar, K., Schlossman, R. L., Richardson, P., and Anderson, K. C. Novel therapies targeting the myeloma cell and its bone marrow microenvironment. Semin. Oncol., 28: 607-612, 2001.
35. Thomas, D. A., and Kantarjian, H. M. Current role of thalidomide in cancer treatment. Curr. Opin. Oncol., 12: 564-573, 2000.
36. Thomas, D. A., Giles, F. J., Cortes, J., Albitar, M., and Kantarjian, H. M. Antiangiogenic therapy in leukemia. Acta Haematol., 106: 190-207, 2001.
37. Neben, K., Moehler, T., Egerer, G., Kraemer, A., Hillengass, J., Benner, A., Ho, A. D., and Goldschmidt, H. High plasma basic fibroblast growth factor concentration is associated with response to thalidomide in progressive multiple myeloma. Clin. Cancer Res., 7: 2675-2681, 2001.
38. Tosi, P., Zamagni, E., Cellini, C., Ronconi, S., Patriarca, F., Ballerini, F., Musto, P., Di Raimondo, F., Ledda, A., Lauria, F., Masini, L., Gobbi, M., Vacca, A., Ria, R., Cangini, D., Tura, S., Baccarani, M., and Cavo, M. Salvage therapy with thalidomide in patients with advanced relapsed/refractory multiple myeloma. Haematologica, 87: 408-414, 2002.
39. Bertolini, F., Mingrone, W., Alietti, A., Ferrucci, P. F., Cocorocchio, E., Peccatori, F., Cinieri, S., Mancuso, P., Corsini, C., Burlini, A., Zucca, E., Martinelli, G., and Cineri, S. Thalidomide in multiple myeloma, myelodysplastic syndromes and histiocytosis. Analysis of clinical results and of surrogate angiogenesis markers. Ann. Oncol., 12: 987-990, 2001.
40. Rajkumar, S. V., Dispenzieri, A., Fonseca, R., Lacy, M. Q., Geyer, S., Lust, J. A., Kyle, R. A., Greipp, P. R., Gertz, M. A., and Witzig, T. E. Thalidomide for previously untreated indolent or smoldering multiple myeloma. Leukemia, 15: 1274-1276, 2001.
41. Neben, K., Moehler, T., Kraemer, A., Benner, A., Egerer, G., Ho, A. D., and Goldschmidt, H. Response to thalidomide in progressive multiple myeloma is not mediated by inhibition of angiogenic cytokine secretion. Br. J. Haematol., 115: 605-608, 2001.
42. Gelderblom, H., Verweij, J., Nooter, K., and Sparreboom, A. Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur. J. Cancer, 37: 1590-1598, 2001.
43. Michaud, L. B. Methods for preventing reactions secondary to Cremophor EL. Ann. Pharmacother., 31: 1402-1404, 1997.
44. Antonian, L., Zhang, H., Yang, C., Wagner, G., Shawver, L. K., Shet, M., Ogilvie, B., Madan, A., and Parkinson, A. Biotransformation of the anti-angiogenic compound SU5416. Drug Metab. Dispos., 28: 1505-1512, 2000.
45. Singer, M. I., Shapiro, L. E., and Shear, N. H. Cytochrome P-450 3A: interactions with dermatologic therapies. J. Am. Acad. Dermatol., 37: 765-771, 1997.
46. Amsden, G. W. Macrolides versus azalides: a drug interaction update. Ann. Pharmacother., 29: 906-917, 1995.
47. Maskalyk, J. Grapefruit juice: potential drug interactions. Can. Med. Assoc. J., 167: 279-280, 2002.
48. Berenson, J. R., Sjak-Shie, N. N., and Vescio, R. A. The role of human and viral cytokines in the pathogenesis of multiple myeloma. Semin. Cancer Biol., 10: 383-391, 2000.
49. Masood, R., Cesarman, E., Smith, D. L., Gill, P. S., and Flore, O. Human herpesvirus-8-transformed endothelial cells have functionally activated vascular endothelial growth factor/vascular endothelial growth factor receptor. Am. J. Pathol., 160: 23-29, 2002.
50. Arasteh, K., and Hannah, A. The role of vascular endothelial growth factor (VEGF) in AIDS-related Kaposi's sarcoma. Oncologist, 5: 28-31, 2000.
51. Masood, R., Cai, J., Zheng, T., Smith, D. L., Naidu, Y., and Gill, P. S. Vascular endothelial growth factor/vascular permeability factor is an autocrine growth factor for AIDS-Kaposi sarcoma. Proc. Natl. Acad. Sci. USA, 94: 979-984. 1997.
52. Angelov, L., Salhia, B., Roncari, L., McMahon, G., and Guha, A. Inhibition of angiogenesis by blocking activation of the vascular endothelial growth factor receptor 2 leads to decreased growth of neurogenic sarcomas. Cancer Res., 59: 5536-5541, 1999.
53. Kyle, R. A., and Rajkumar, S. V. Therapeutic application of thalidomide in multiple myeloma. Semin. Oncol., 28: 583-587, 2001.
54. Treon, S., Mitsiades, C. S., Poulaki, V., Anderson, K. C., and Mitsiades, N. Concepts in the use of TRAIL/Apo2L: an emerging biotherapy for myeloma and other neoplasias. Expert Opin. Investig. Drugs, 10: 1521-1530, 2001.
55. Tsimberidou, A. M., and Giles, F. J. TNF-α targeted therapeutic approaches in patients with hematologic malignancies. Expert Rev. Anticancer Ther., 2: 277-286, 2002.
56. Dmoszynska, A., Bojarska-Junak, A., Domanski, D., Rolinski, J., Hus, M., and Soroka-Wojtaszko, M. Production of proangiogenic cytokines during thalidomide treatment of multiple myeloma. Leuk. Lymphoma, 43: 401-406, 2002.
57. Sato, N., Hattori, Y., Wenlin, D., Yamada, T., Kamata, T., Kakimoto, T., Okamoto, S., Kawamura, C., Kizaki, M., Shimada, N., Ote, Y., Hata, J., and Ikeda, Y. Elevated level of plasma basic fibroblast growth factor in multiple myeloma correlates with increased disease activity. Jpn. J. Cancer Res., 93: 459-466, 2002.
58. Yoshiji, H., Harris, S. R., and Thorgeirsson, U. P. Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells. Cancer Res., 57: 3924-3928, 1997.
59. Desai, S. B., and Libutti, S. K. Tumor angiogenesis and endothelial cell modulatory factors. J. Immunother., 22: 186-211, 1999.
60. Bouck, N., Stellmach, V., and Hsu, S. C. How tumors become angiogenic. Adv. Cancer Res., 69: 135-174, 1996.
61. Roboz, G. J., Dias, S., Lam, G., Lane, W. J., Soignet, S. L., Warrell, R. P., Jr., and Rafii, S. Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis. Blood, 96: 1525-1530, 2000.
62. Baidas, S., Tfayli, A., and Bhargava, P., Thalidomide: an old drug with new clinical applications. Cancer Investig., 20: 835-848, 2002.
63. Klausner, J. D., Freedman, V. H., and Kaplan, G. Thalidomide as an anti-TNF-α inhibitor: implications for clinical use, Clin. Immunol. Immunopathol., 81: 219-223, 1996.
64. Orpana, A., and Salven, P. Angiogenic and lymphangiogenic molecules in hematological malignancies. Leuk. Lymphoma, 43: 219-224, 2002.
65. Tsimberidou, A. M., Thomas, D., O'Brien, S., Andreeff, M., Kurzrock, R., Keating, M., Albitar, M., Kantarjian, H., and Giles, F. Recombinant human soluble tumor necrosis factor (TNF) receptor (p75) fusion protein Enbrel in patients with refractory hematologic malignancies. Cancer Chemother. Pharmacol., 50: 237-242, 2002.
66. Wood, J. M., Bold, G., Buchdunger, E., Cozens, R., Ferrari, S., Frei, J., Hofmann, F., Mestan, J., Mett, H., O'Reilly, T., Persohn, E., Rosel, J., Schnell, C., Stover, D., Theuer, A., Towbin, H., Wenger, F., Woods-Cook, K., Menrad, A., Siemeister, G., Schirner, M., Thierauch, K. H., Schneider, M. R., Drevs, J., Martiny-Baron, G., and Totzke, F. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res., 60: 2178-2189, 2000.
67. Mitsiades, N., Mitsiades, C. S., Poulaki, V., Chauhan, D., Richardson, P. G., Hideshima, T., Munshi, N. C., Treon, S. P., and Anderson, K. C. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood, 99: 4525-4530, 2002.
68. Stopeck, A., Sheldon, M., Vahedian, M., Cropp, G., Gosalia, R., and Hannah, A. Results of a phase I dose-escalating study of the antiangiogenic agent, SU5416, in patients with advanced malignancies. Clin. Cancer Res., 8: 2798-2805, 2002.
69. Korn, E. L., Arbuck, S. G., Pluda, J. M., Simon, R., Kaplan, R. S., and Christian, M. C. Clinical trial designs for cytostatic agents: are new approaches needed? J. Clin. Oncol., 19: 265-272, 2001.