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Blood, 20 August 2009, Vol. 114, No. 8, pp. 1489-1497. Prepublished online as a Blood First Edition Paper on June 4, 2009; DOI 10.1182/blood-2009-02-203398.
CLINICAL TRIALS AND OBSERVATIONS Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study1 Princess Margaret Hospital, Toronto, ON; 2 Boston University Medical Center, MA; 3 Amyloidosis Center, University of Heidelberg, Heidelberg, Germany; 4 Center for Amyloidosis, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, University of Pavia, Pavia, Italy; 5 Hôpital Saint Louis, Paris, France; 6 Cedars-Sinai Medical Center, Los Angeles, CA; 7 Johnson & Johnson Oncology Research & Development, Raritan, NJ; 8 Johnson & Johnson Oncology Research & Development, High Wycombe, United Kingdom; and 9 Memorial Sloan-Kettering Cancer Center, New York, NY 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/m2; days 1, 8, 15, and 22; 35-day cycles) and twice weekly (0.7-1.3 mg/m2; 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/m2, and 1 at twice weekly, 1.0 mg/m2). MTD was not defined for either schedule; the maximum doses of 1.6 mg/m2 (once weekly) and 1.3 mg/m2 (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 [ClinicalTrials.gov] .
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