A phase I study using bortezomib with weekly idarubicin for treatment of elderly patients with acute myeloid leukemia.
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 1.2 mg/m(2) with once weekly idarubicin 10 mg/m(2) 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 0.8 mg/m(2) and idarubicin 10 mg/m(2)); idarubicin was reduced to 8 mg/m(2) without observing subsequent dose-limiting toxicities. The maximum tolerated dose in this study was bortezomib 1.2 mg/m(2) and idarubicin 8 mg/m(2). 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.
Markey Cancer Center, University of Kentucky, Lexington, KY, United States. Electronic address: DSHowa0@uky.edu.
Dianna S
DS
Howard
Jane
J
Liesveld
Gordon L
GL
Phillips
John
J
Hayslip
Heidi
H
Weiss
Craig T
CT
Jordan
Monica L
ML
Guzman
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage; D012074:Remission Induction; D015996:Survival Rate
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D015255:Idarubicin
AML; Acute myeloid leukemia; Bortezomib; DLT; DSMC; Data Safety Monitoring Committee; EMSA; Elderly; FACS; Idarubicin; LSC; MDS; MTD; NF-kB; acute myeloid leukemia; dose-limiting toxicity; electrophoretic mobility shift assay; fluorescence-activated cell sorting; iKBa; inhibitor of NF-kB; leukemic stem cell; maximum tolerated dose; myelodysplastic syndrome; nuclear factor kappa B