Bortezomib in a phase 1 trial for patients with relapsed AL amyloidosis: Cardiac responses and overall effects Journal Article
| Authors: | Dubrey, S. W.; Reece, D. E.; Sanchorawala, V.; Hegenbart, U.; Merlini, G.; Palladini, G.; Fermand, J. P.; Vescio, R. A.; Blade, J.; Heffner, L. T.; Hassoun, H.; Liu, X.; Enny, C.; Ramaswami, P.; Elsayed, Y.; van de Velde, H.; Mortimer, S.; Cakana, A.; Comenzo, R. L. |
| Article Title: | Bortezomib in a phase 1 trial for patients with relapsed AL amyloidosis: Cardiac responses and overall effects |
| Abstract: | 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. © The Author 2011. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. |
| Keywords: | adult; clinical article; treatment outcome; treatment response; aged; middle aged; prednisone; fatigue; disease classification; drug safety; drug withdrawal; hypertension; side effect; treatment duration; antineoplastic agents; prospective studies; edema; bortezomib; multiple cycle treatment; boronic acids; pyrazines; drug administration schedule; cohort analysis; relapse; amyloidosis; kidney failure; dose-response relationship, drug; asthenia; dizziness; drug dose escalation; dyspnea; syncope; heart palpitation; hypotension; thorax pain; disease progression; heart failure; patient safety; peripheral edema; single drug dose; nausea and vomiting; liver diseases; interstitial lung disease; maximum tolerated dose; phase 1 clinical trial; echocardiography; heart left ventricle ejection fraction; brain ischemia; neurologic disease; gastrointestinal disease; electrocardiography; congestive heart failure; peripheral nervous system diseases; bronchitis; heart diseases; falling; paraproteinemias; kidney diseases; heart left ventricle hypertrophy; escherichia coli infection; holter monitoring; lobar pneumonia; orthostatic hypertension; primary systemic light chain amyloidosis; staphylococcal bacteremia |
| Journal Title: | QJM: An International Journal of Medicine |
| Volume: | 104 |
| Issue: | 11 |
| ISSN: | 1460-2725 |
| Publisher: | Oxford University Press |
| Date Published: | 2011-11-01 |
| Start Page: | 957 |
| End Page: | 970 |
| Language: | English |
| DOI: | 10.1093/qjmed/hcr105 |
| PROVIDER: | scopus |
| PUBMED: | 21752867 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 February 2012" - "Art. No.: hcr105" - "CODEN: QMJPF" - "Source: Scopus" |
