Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: Results of a phase 1 dose-escalation study Journal Article
| Authors: | Reece, D. E.; Sanchorawala, V.; Hegenbart, U.; Merlini, G.; Palladini, G.; Fermand, J. P.; Vescio, R. A.; Liu, X.; Elsayed, Y. A.; Cakana, A.; Comenzo, R. L. |
| Article Title: | Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: Results of a phase 1 dose-escalation study |
| Abstract: | New treatment options are required for primary systemic AL amyloidosis (AL). This phase 1 dose-escalation component of a phase 1/2 study in relapsed AL aimed to determine the maximum tolerated dose (MTD) of bortezomib once weekly (0.7-1.6 mg/m<sup>2</sup>; days 1, 8, 15, and 22; 35-day cycles) and twice weekly (0.7-1.3 mg/m<sup>2</sup>; days 1, 4, 8, and 11; 21-day cycles) and assess preliminary hematologic responses. Thirty-one patients with relapsed AL were enrolled across 7 cohorts. Dose-limiting toxicity included grade 3 congestive heart failure in 2 patients (1 at once weekly, 1.6 mg/m<sup>2</sup>, and 1 at twice weekly, 1.0 mg/m<sup>2</sup>). MTD was not defined for either schedule; the maximum doses of 1.6 mg/m<sup>2</sup>(once weekly) and 1.3 mg/m<sup>2</sup> (twice weekly) are being used in phase 2 evaluation. Most commonly reported toxicities on both schedules included gastrointestinal events, fatigue, and nervous system disorders. Discontinuations and dose reductions for toxicity were reported in 12 and 4 patients, respectively. No treatment-related deaths occurred. Hematologic responses occurred in 15 (50%) of 30 evaluable patients, including 6 (20%) complete responses. Median time to first response was 1.2 months. Once-weekly and twice-weekly bortezomib appear generally well tolerated in relapsed AL, with promising hematologic responses. This study is registered with http://ClinicalTrials.gov under identifier NCT00298766. © 2009 by The American Society of Hematology. |
| Keywords: | adult; clinical article; controlled study; human tissue; treatment outcome; treatment response; aged; middle aged; clinical trial; constipation; fatigue; paresthesia; diarrhea; dose response; drug dose reduction; drug efficacy; drug safety; drug withdrawal; side effect; antineoplastic agents; antineoplastic agent; anorexia; edema; bortezomib; drug eruption; multiple cycle treatment; sensory neuropathy; boronic acids; pyrazines; gastrointestinal symptom; nausea; thrombocytopenia; vomiting; drug administration schedule; orthostatic hypotension; relapse; amyloidosis; dose-response relationship, drug; abdominal pain; arthralgia; asthenia; backache; coughing; dizziness; drug dose escalation; drug fever; dyspnea; pruritus; heart palpitation; hypotension; insomnia; adverse outcome; multicenter study; peripheral edema; xerostomia; anxiety; headache; maximum tolerated dose; phase 1 clinical trial; drug administration; dyspepsia; muscle spasm; influenza; neurologic disease; herpes; boronic acid derivative; pyrazine derivative; congestive heart failure; bronchitis; upper respiratory tract infection; night sweat; hypesthesia; sore throat; abdominal distension; hyperhidrosis; rhinopharyngitis |
| Journal Title: | Blood |
| Volume: | 114 |
| Issue: | 8 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2009-08-20 |
| Start Page: | 1489 |
| End Page: | 1497 |
| Language: | English |
| DOI: | 10.1182/blood-2009-02-203398 |
| PUBMED: | 19498019 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 30 November 2010" - "CODEN: BLOOA" - "Source: Scopus" |
