We report the results of a phase I study with four dose levels of bortezomib in combination with idarubicin. Eligible patients were newly diagnosed with acute myeloid leukemia (AML) age ≥60 years, or any adult with relapsed AML. Bortezomib was given twice weekly at 0.8, 1.0, or 1.2mg/m2 with once weekly idarubicin 10mg/m2 for four weeks. Twenty patients were treated: 13 newly diagnosed (median age 68, range 61-83) and 7 relapsed (median age 58, range 40-77). Prior myelodysplastic syndrome (MDS) was documented in 10/13 (77%) newly diagnosed and 1/7 (14%) relapsed patients; the three newly diagnosed patients without prior MDS had dyspoietic morphology. Two dose-limiting toxicities occurred at the initial dose level (bortezomib 0.8mg/m2 and idarubicin 10mg/m2); idarubicin was reduced to 8mg/m2 without observing subsequent dose-limiting toxicities. The maximum tolerated dose in this study was bortezomib 1.2mg/m2 and idarubicin 8mg/m2. Common adverse events included: neutropenic fever, infections, constitutional symptoms, and gastrointestinal symptoms. No subjects experienced neurotoxicity. Most patients demonstrated hematologic response as evidenced by decreased circulating blasts. Four patients (20%) achieved complete remission. There was one treatment-related death. The combination of bortezomib and idarubicin in this mostly poor-risk, older AML group was well tolerated and did not result in high mortality. This trial was registered at www.clinicaltrials.gov as #NCT00382954.
|Number of pages||7|
|State||Published - Nov 2013|
Bibliographical noteFunding Information:
Funding : This study was supported by Millennium Pharmaceuticals and NIH/NCI grant R21 CA108162-01A1 , neither of which were involved in the study design, collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.
- Acute myeloid leukemia
ASJC Scopus subject areas
- Cancer Research