Effective strategies for management of hypertension after vascular endothelial growth factor signaling inhibition therapy: results from a phase II randomized, factorial, double-blind study of Cediranib in patients with advanced solid tumors
| Autor: | Walter Fiedler, Emile E. Voest, Jan H.M. Schellens, Jane Robertson, Florence Le Maulf, Carla M.L. van Herpen, Anitra Fielding, Johann S. de Bono, Hubert E. Blum, Clemens Unger, Joachim Drevs, Marlies H.G. Langenberg, Klaas Hoekman |
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| Přispěvatelé: | Medical oncology, CCA - Innovative therapy |
| Rok vydání: | 2009 |
| Předmět: |
Oncology
Adult Male Vascular Endothelial Growth Factor A Cancer Research medicine.medical_specialty Randomization law.invention Cediranib chemistry.chemical_compound Young Adult Randomized controlled trial Double-Blind Method Translational research [ONCOL 3] law Internal medicine Neoplasms Medicine Humans Prospective Studies Adverse effect Prospective cohort study Antihypertensive Agents Aged Dose-Response Relationship Drug business.industry Middle Aged Surgery Clinical trial Vascular endothelial growth factor Blood pressure chemistry Hypertension Quinazolines Female business medicine.drug Signal Transduction |
| Zdroj: | Langenberg, M H G, van Herpen, C M L, De Bono, J, Schellens, J H M, Unger, C, Hoekman, K, Blum, H E, Fiedler, W, Drevs, J, Le Maulf, F, Fielding, A, Robertson, J & Voest, E E 2009, ' Effective Strategies for Management of Hypertension After Vascular Endothelial Growth Factor Signaling Inhibition Therapy: Results From a Phase II Randomized, Factorial, Double-Blind Study of Cediranib in Patients With Advanced Solid Tumors ', Journal of Clinical Oncology, vol. 27, no. 36, pp. 6152-6159 . https://doi.org/10.1200/JCO.2009.22.2273 Journal of Clinical Oncology, 27(36), 6152-6159. American Society of Clinical Oncology Journal of Clinical Oncology, 27, 6152-9 Journal of Clinical Oncology, 27, 36, pp. 6152-9 |
| ISSN: | 0732-183X |
| DOI: | 10.1200/JCO.2009.22.2273 |
| Popis: | Purpose Hypertension is a commonly reported adverse effect after administration of vascular endothelial growth factor (VEGF) inhibitors. Cediranib is a highly potent and selective VEGF signaling inhibitor of all three VEGFRs. This study prospectively investigated hypertension management to help minimize dose interruptions/reductions to maximize cediranib dose intensity. Patients and Methods Patients (n = 126) with advanced solid tumors were randomly assigned to one of four groups: cediranib 30 or 45 mg/d with or without antihypertensive prophylaxis. All patients developing hypertension on cediranib treatment were treated with a standardized, predefined hypertension management protocol. Results Cediranib was generally well tolerated, and all groups achieved high-dose intensities in the first 12 weeks (> 74% in all groups). Antihypertensive prophylaxis did not result in fewer dose reductions or interruptions. Increases in blood pressure, including moderate and severe readings of hypertension, were seen early in treatment in all groups and successfully managed. Severe hypertension occurred in one patient receiving prophylaxis versus 18 in the nonprophylaxis groups. Overall, there were nine partial responses, and 38 patients experienced stable disease ≥ 8 weeks. Conclusion To our knowledge, this is the first prospective investigation of hypertension management during administration of a VEGF signaling inhibitor. All four regimens were well tolerated with high-dose intensities and no strategy was clearly superior. The current cediranib hypertension management protocol appears to be effective in managing hypertension compared with previous cediranib studies where no plan was in place, and early recognition and treatment of hypertension is likely to reduce the number of severe hypertension events. This protocol is included in all ongoing cediranib clinical studies. |
| Databáze: | OpenAIRE |
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