+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Phase II study of SU5416, a small molecule vascular endothelial growth factor tyrosine kinase receptor inhibitor, in patients with refractory multiple myeloma



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 10(1 Pt 1): 88-95



Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with multiple myeloma (MM). VEGF, a soluble circulating angiogenic molecule, acts via receptor tyrosine kinases, including VEGF receptor 2. SU5416 is a small molecule VEGF receptor 2 inhibitor. Adult patients with advanced MM were entered on a multicenter phase II study. Twenty-seven patients (median age 69, range 39-79), median 4 (0-10) lines of prior therapy, 14 with prior thalidomide therapy, received SU5416 at 145 mg/m(2) twice weekly i.v. for a median of two 4-week cycles (range 0.2-9). Grade 3/4 toxicities were rarely observed; the most frequent was thrombocytopenia (12%). Mild-to-moderate toxicities included nausea (63%), headache (56%), diarrhea, vomiting (both 37%), and fatigue (33%). There were three thromboembolic episodes and five cases of new onset hypertension. Two (7%) patients did not complete the first 4-week cycle of therapy because of adverse events (pneumonia and headache). There were no objective responses. Four patients had disease stabilization for >/==" BORDER="0">4 months. A decrease in median VEGF plasma levels was observed in patients with stable disease (n = 7) compared with patients with progressive disease (n = 5). Overall median survival was 42 weeks (range 3-92+). Although SU5416 had minimal clinical activity, signs of biological activity (decrease in plasma VEGF levels) suggest that angiogenic modulation may be of value in patients with MM.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 049909460

Download citation: RISBibTeXText

PMID: 14734456

DOI: 10.1158/1078-0432.ccr-0221-3


Related references

Phase II study of SU5416--a small-molecule, vascular endothelial growth factor tyrosine-kinase receptor inhibitor--in patients with refractory myeloproliferative diseases. Cancer 97(8): 1920-1928, 2003

Phase I study of SU5416, a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR) in refractory pediatric central nervous system tumors. Pediatric Blood and Cancer 52(2): 169-176, 2009

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. Clinical Cancer Research 9(4): 1546-1556, 2003

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 Research 59(1): 99-106, 1999

Effects of Su5416, a small molecule tyrosine kinase receptor inhibitor, on Flt3 expression and phosphorylation in patients with refractory acute myeloid leukemia. Leukemia Research 28(7): 679-689, 2004

SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes. Blood 102(3): 795-801, 2003

Effects of SU5416, a small molecule tyrosine kinase receptor inhibitor, on FLT3 expression and phosphorylation in patients with refractory acute myeloid leukemia. Leukemia Research 28(7): 679-689, 2004

Antitumor activity of ZD6474, a vascular endothelial growth factor-2 and epidermal growth factor receptor small molecule tyrosine kinase inhibitor, in combination with SC-236, a cyclooxygenase-2 inhibitor. Clinical Cancer Research 11(3): 1268-1276, 2005

Phase I dose escalation and pharmacokinetic study of AZD2171, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinase, in patients with hormone refractory prostate cancer (HRPC). Investigational new Drugs 25(5): 445-451, 2007

Inhibition of angiogenesis and tumor growth by AG13925, a small molecule inhibitor of vascular endothelial growth factor receptor tyrosine kinase. Proceedings of the American Association for Cancer Research Annual Meeting 42: 584, 2001

Phase II data with ZD6474, a small-molecule kinase inhibitor of epidermal growth factor receptor and vascular endothelial growth factor receptor, in previously treated advanced non-small-cell lung cancer. Clinical Lung Cancer 7(2): 89-91, 2005

Inhibitory effects of SU5416, a selective vascular endothelial growth factor receptor tyrosine kinase inhibitor, on experimental corneal neovascularization. Ophthalmic Research 47(1): 13-18, 2012

The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment. European Journal of Haematology 70(4): 266-267, 2003

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 Research 62(17): 5019-5026, 2002

Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. Journal of Clinical Oncology 23(11): 2544-2555, 2005