Phase II Study of SU5416, a Small Molecule Vascular Endothelial Growth Factor Tyrosine Kinase Receptor Inhibitor, in Patients with Refractory Multiple Myeloma
| Autor: | Elias Anaissie, Stephan Faderl, Maureen Cooper, Alison L. Hannah, Maurizio Zangari, Nguyen Tan, Maher Albitar, Alison Stopeck, Guillermo Garcia-Manero, Hagop M. Kantarjian, Julie M. Cherrington, Francis J. Giles, Alyssa Morimoto, Jeffrey E. Lancet |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Vascular Endothelial Growth Factor A Cancer Research medicine.medical_specialty Indoles Angiogenesis Salvage therapy Angiogenesis Inhibitors Gastroenterology chemistry.chemical_compound Internal medicine Biomarkers Tumor medicine Humans Pyrroles Enzyme Inhibitors Adverse effect Survival rate Multiple myeloma Aged Salvage Therapy Neovascularization Pathologic business.industry Remission Induction Middle Aged Protein-Tyrosine Kinases medicine.disease Vascular Endothelial Growth Factor Receptor-2 Thalidomide Survival Rate Vascular endothelial growth factor Endocrinology Oncology chemistry Drug Resistance Neoplasm Female Multiple Myeloma business Progressive disease medicine.drug |
| Zdroj: | Clinical Cancer Research. 10:88-95 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-0221-3 |
| Popis: | Purpose: 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. Experimental Design: Adult patients with advanced MM were entered on a multicenter phase II study. Results: 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/m2 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 ≥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+). Conclusions: 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. |
| Databáze: | OpenAIRE |
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