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.
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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. / Langenberg, Marlies H G; Herpen, van; Carla, M L; Johann, De Bono; Schellens, Jan H M; Unger, Clemens; Hoekman, Klaas; Fiedler, Walter; Fiedler, Walter; Drevs, Joachim; Florence, Le Maulf; Fielding, Anitra; Robertson, Jane; Voest, Emile E.
in: J CLIN ONCOL, Jahrgang 27, Nr. 36, 36, 2009, S. 6152-6159.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - 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.
AU - Langenberg, Marlies H G
AU - Herpen, van
AU - Carla, M L
AU - Johann, De Bono
AU - Schellens, Jan H M
AU - Unger, Clemens
AU - Hoekman, Klaas
AU - Fiedler, Walter
AU - Fiedler, Walter
AU - Drevs, Joachim
AU - Florence, Le Maulf
AU - Fielding, Anitra
AU - Robertson, Jane
AU - Voest, Emile E
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 27
SP - 6152
EP - 6159
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 36
M1 - 36
ER -
