Abstract
9021 Background: Bortezomib is a 26S proteasome inhibitor that is effective as a single agent for the treatment of multiple myeloma in adults. Bortezomib at a dose of 1.2 mg/m2 is well tolerated as a single agent in pediatric patients with solid tumors. This phase 1 study examined the tolerability and efficacy of bortezomib in pediatric patients with relapsed/refractory leukemia. Methods: Cohorts of 3–6 patients received bortezomib administered twice weekly (days 1, 4, 8 and 11) for two weeks every 21 days. Pharmacokinetics and NF-κB activation status were examined in peripheral blood mononuclear cells (PBMC) at 6, 12, and 24 hours following the first dose of bortezomib, and from bone marrow leukemic cells before treatment and on days 8 and 18 of the first treatment cycle. Results: Twelve patients (4 female, 8 male) (ALL=9, AML=3), median age 11y (range 1–18y), were enrolled at the 1.3 mg/m2 (6 enrolled, 3 evaluable) or 1.7 mg/m2 (6 enrolled, 2 evaluable) dose levels. Patients not fully evaluable for toxicity experienced disease progression prior to completing the first 21-day cycle of therapy. Two DLTs occurred at the 1.7 mg/m2 dose level. One patient had altered mental status and the other patient had febrile neutropenia associated with Grade 3 hypotension, Grade 4 renal insufficiency and hypoxia, followed by death on day 9 of cycle 1. No CRs or PRs were observed in the 10 patients evaluable for response. One patient had SD for 2 cycles. PK analysis (n= 5) revealed a Cl of 0.62 L/min/m2, Vd of 13 L/m2, and a terminal T1/2 of 12.6 h. NF-κB activation was inhibited in the leukemic blasts of 2 patients examined to date. Conclusions: Bortezomib was tolerated at 1.3 mg/m2 in children with relapsed/refractory leukemia. Although bortezomib appeared to inhibit NF-κB activation, it was ineffective as a single agent for pediatric leukemia treatment. No significant financial relationships to disclose.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
