Phase II study of SU5416—a small-molecule, vascular endothelial growth factor tyrosine-kinase receptor inhibitor—in patients with refractory myeloproliferative diseases
| العنوان: | Phase II study of SU5416—a small-molecule, vascular endothelial growth factor tyrosine-kinase receptor inhibitor—in patients with refractory myeloproliferative diseases |
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| المؤلفون: | Lewis Silverman, Guillermo Garcia-Manero, Paul J. Shami, Judith E. Karp, Maurizio Zangari, Maher Albitar, Khuda D. Khan, Deborah A. Thomas, Hagop Kantarjian, Jeffrey E. Lancet, Alison T. Stopeck, Julie M. Cherrington, Maureen A. Cooper, Alison L. Hannah, Francis J. Giles |
| المصدر: | Cancer. 97:1920-1928 |
| بيانات النشر: | Wiley, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Adult, Male, Vascular Endothelial Growth Factor A, Cancer Research, medicine.medical_specialty, Indoles, medicine.drug_class, medicine.medical_treatment, Fusion Proteins, bcr-abl, Chronic myelomonocytic leukemia, Endothelial Growth Factors, Gastroenterology, Tyrosine-kinase inhibitor, chemistry.chemical_compound, Bone Marrow, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Pyrroles, Bone pain, Myelofibrosis, Aged, Aged, 80 and over, Lymphokines, Chemotherapy, Myeloproliferative Disorders, Vascular Endothelial Growth Factors, business.industry, Myeloid leukemia, Middle Aged, Protein-Tyrosine Kinases, medicine.disease, Vascular Endothelial Growth Factor Receptor-2, Vascular endothelial growth factor, Endocrinology, Oncology, chemistry, Intercellular Signaling Peptides and Proteins, Female, medicine.symptom, business, Progressive disease |
| الوصف: | BACKGROUND Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with myeloproliferative disorders (MPD), including agnogenic myeloid metaplasia (AMM), chronic myeloid leukemia in blastic phase (CML-BP), and chronic myelomonocytic leukemia (CMML). VEGF is a soluble, circulating, angiogenic molecule that acts through receptor tyrosine kinases (RTK), including VEGF receptor 2 (VEGFR-2). SU5416 is a small-molecule RTK inhibitor (RTKI) that targets VEGFR-2, c-kit, and fms-related tyrosine kinase Flk2. METHODS Adult patients with advanced CMML, AMM, CML-BP, or other BCR-ABL negative MPD were entered on a multicenter, Phase II study. RESULTS Thirty-two patients (19 patients with BCR-ABL negative MPD, 6 patients with CMML, 4 patients with CML-BP, and 3 patients with AMM) with a median age of 66 years (range, 29–85 years) received SU5416 145 mg/m2 twice weekly intravenously for a median of three 4-week cycles (maximum, 12 cycles). Drug-related Grade 3–4 toxicities included acute abdominal pain (13%), bone pain (9%), infusion-related dyspnea (9%) or headache (6%), fatigue (6%), diarrhea (3%), and catheter site reactions (3%). Eleven patients (34%) did not receive a second cycle of therapy (6 patients had progressive disease, 3 because of adverse events; 2 patients withdrew due to lack of response). One patient with AMM achieved a partial response. Eight patients received more than 6 months of therapy. CONCLUSIONS SU5416 had minimal clinical activity in patients with MPD. Long-term administration of a twice-weekly, hyperosmolar, intravenous solution containing polyoxyl 35 castor oil was difficult. More tolerable RTKI may be worthy of further investigation in patients with MPD. Cancer 2003;97:1920–8. © 2003 American Cancer Society. DOI 10.1002/cncr.11315 |
| تدمد: | 1097-0142 0008-543X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68edbaed758ad21423669d123e07c3fa https://doi.org/10.1002/cncr.11315 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....68edbaed758ad21423669d123e07c3fa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970142 0008543X |
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