A phase I safety and PK study of the novel vascular targeting agent (VTA), Exherin, in patients with refractory solid tumors stratified according to N-cadherin expression
| Autor: | R. Goel, David J. Stewart, Derek J. Jonker, Glenwood D. Goss, L. Avruch, W. P. Peters, T. A. Spencer, M. N. Reaume, Susan Dent |
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| Rok vydání: | 2004 |
| Předmět: |
Drug
Cancer Research Cadherin business.industry media_common.quotation_subject Pharmacology Endothelial stem cell chemistry.chemical_compound medicine.anatomical_structure Oncology Pharmacokinetics chemistry Refractory Dynamic contrast-enhanced MRI medicine Cancer research Vascular-targeting agent Pericyte business media_common |
| Zdroj: | Journal of Clinical Oncology. 22:3078-3078 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 3078 Background: Exherin is a novel angiolytic VTA which specifically targets existing tumor vessels. Exherin is a cyclic pentapeptide (CHAVC) which competitively inhibits N-cadherin mediated endothelial cell, pericyte and tumor cell binding. Exherin caused highly-specific tumor angiolysis in multiple murine and xenograft tumor models. We report here preliminary data from the first human safety and pharmacokinetics (PK) study on Exherin. Methods: 13 patients (pts) with refractory solid tumors received 24 cycles of Exherin by bolus injection at 4 dose levels from 50 to 225 mg/m2to define the toxicities (AE) and maximum tolerated dose (MTD) for patients with N-cadherin positive or negative tumors. Dynamic MRI was performed in cohorts 3 to 5 where feasible to assess for changes in tumor perfusion and intra-tumoral hemorrhage. Results: Dose escalation has proceeded without reaching MTD. AE > grade 2 considered possibly drug related include tumor pain (n=3) and 1 coronary syndrome in a patient with a previousl... |
| Databáze: | OpenAIRE |
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