In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 6526-6526
Abstract:
6526 Background: We conducted a clinical trial to determine the complete remission (CR) rate in older AML patients treated with bortezomib (Bz) plus daunorubicin and cytarabine induction therapy and the maximal tolerated dose (MTD) of Bz when added to Int-DAC consolidation therapy. Methods: Ninety-five adults (60-75 yrs old; median, 67) with previously untreated AML (including therapy-related and prior MDS) received Bz 1.3 mg/m 2 IV on days 1, 4, 8 and 11 with daunorubicin 60 mg/m 2 on days 1-3 and cytarabine 100 mg/m 2 by continuous IV infusion on days 1-7. Patients who achieved a CR received 2 courses of consolidation chemotherapy with cytarabine 2 gm/m 2 over 3 hours on days 1-5 (Int-DAC) with Bz administered on days 1, 4, 8 and 11. Three cohorts with escalating dose levels of Bz were tested (0.7, 1.0, and 1.3 mg/m 2 ). Dose limiting toxicities were assessed during the first cycle of consolidation. Predictors of response, including CD74 expression, were assessed. Results: The CR frequency was 65% (62/95). An additional 4% (4/95) achieved CR with incomplete platelet recovery. The CR rate according to ELN Genetic Groups was 90% (9/10) for favorable, 71% (12/17) for Int-I, 52% (17/33) for Int-II, and 46% (5/11) for adverse. Six patients had grade 3 sensory neuropathy. There were 6 treatment-related deaths during cycle 1 of induction and 2 during cycle 2. Bz plus Int-DAC proved tolerable at the highest dose tested. The median disease-free (DFS) and overall survivals (OS) for patients on this study were 8.2 and 12.1 months, respectively. Lower CD74 expression was associated with CR/CRp (p=.04) but not with DFS or OS. Conclusions: The addition of Bz 1.3 mg/m 2 IV on days 1, 4, 8, and 11 to standard “3 + 7” daunorubicin and cytarabine induction chemotherapy for AML is well tolerated and results in a remission rate at least as high as would be expected with ”3+7” alone in older patients. The maximum tested dose of Bz given in combination with Int-DAC for remission consolidation was 1.3 mg/m 2 and proved to be tolerable. Further testing of this regimen in a phase III study is planned.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.6526
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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