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Bortezomib in a phase 1 trial for patients with relapsed AL amyloidosis: cardiac responses and overall effects

Background: Bortezomib is approved for the treatment of multiple myeloma and a role has been suggested in the treatment of systemic AL amyloidosis (AL).Methods: In this phase 1 dose-escalation portion of the first prospective study of single-agent bortezomib in AL, 31 patients with relapsed disease,...

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Hauptverfasser: Dubrey, Simon (VerfasserIn) , Reece, D.E. (VerfasserIn) , Sanchorawala, V. (VerfasserIn) , Hegenbart, Ute (VerfasserIn) , Merlini, G. (VerfasserIn) , Palladini, G. (VerfasserIn) , Fermand, J.-P. (VerfasserIn) , Vescio, R.A. (VerfasserIn) , Bladé, J. (VerfasserIn) , Heffner, L.T. (VerfasserIn) , Hassoun, H. (VerfasserIn) , Liu, X. (VerfasserIn) , Enny, C. (VerfasserIn) , Ramaswami, P. (VerfasserIn) , Elsayed, Y. (VerfasserIn) , Van De Velde, H. (VerfasserIn) , Mortimer, S. (VerfasserIn) , Cakana, A. (VerfasserIn) , Comenzo, R.L. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 13 July 2011
In: QJM
Year: 2011, Jahrgang: 104, Heft: 11, Pages: 957-970
ISSN:1460-2393
DOI:10.1093/qjmed/hcr105
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/qjmed/hcr105
Volltext
Verfasserangaben:S.W. Dubrey, D.E. Reece, V. Sanchorawala, U. Hegenbart, G. Merlini, G. Palladini, J.-P. Fermand, R.A. Vescio, J. Bladé, L.T. Heffner, H. Hassoun, X. Liu, C. Enny, P. Ramaswami, Y. Elsayed, H. Van De Velde, S. Mortimer, A. Cakana and R.L. Comenzo for the Velcade Can2007 study group
Beschreibung
Zusammenfassung:Background: Bortezomib is approved for the treatment of multiple myeloma and a role has been suggested in the treatment of systemic AL amyloidosis (AL).Methods: In this phase 1 dose-escalation portion of the first prospective study of single-agent bortezomib in AL, 31 patients with relapsed disease, including 14 (45%) with cardiac involvement, received bortezomib in seven dose cohorts on once-weekly (0.7, 1.0, 1.3, 1.6 mg/m2) and twice-weekly (0.7, 1.0, 1.3 mg/m2) schedules. Electrocardiographic, Holter and echocardiographic studies were evaluated in all patients to determine safety and response.Results: During therapy (median treatment period 210 days), no patient developed significant ventricular or supraventricular rhythm disturbance on 24-h Holter monitoring; however, no patient satisfied study criteria for cardiac response using echocardiographic assessment or New York Heart Association classification. Seven patients (23%) had a ≥10% fall in left ventricular ejection fraction, but only one met criteria for cardiac deterioration. The predominant cardiac adverse events were peripheral edema (23%), orthostatic hypotension (13%) and hypotension (10%). Two patients developed grade 3 congestive heart failure, which resolved following treatment interruption. In this Phase 1 portion, the maximum tolerated dose of bortezomib on either schedule was not reached. Hematologic responses occurred in 14 patients (45%), including seven (23%) complete responses. In non-responders mean left ventricular wall thickness increased during the course of treatment.Conclusions: AL is frequently rapidly progressive; in these patients who had relapsed or progressed following previous conventional therapies, these results suggest that bortezomib may slow the progression of cardiac amyloid with limited toxicity.
Beschreibung:Gesehen am 30.03.2022
Beschreibung:Online Resource
ISSN:1460-2393
DOI:10.1093/qjmed/hcr105

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