Older patients with untreated acute myeloid leukemia (AML) may benefit from having bortezomib added to daunorubicin and cytarabine during induction therapy and to consolidation intermediate-dose cytarabine (Int-DAC), the results of a US study indicate.
The team, led by Eyal Attar, from Massachusetts General Hospital in Boston, says: "We demonstrated that the combination of bortezomib with 3 + 7 chemotherapy results in an encouraging remission frequency, that bortezomib 1.3 mg/m2 has acceptable toxicity with Int-DAC in consolidation."
For the study, 95 patients aged 60-75 years were given bortezomib 1.3 mg/m2 intravenously on days 1, 4, 8, and 11 with daunorubicin 60 mg/mm2 on days 1-3 and cytarabine 100 mg/m2 by continuous intravenous (iv) infusion on days 1-7. Patients achieving complete remission were given two courses of cytarabine 2 mg/m2 on days 1-5 with bortezomib, again on days 1, 4, 8, and 11.
Complete remission (CR) was achieved by 65% of patients, with an additional 4% achieving CR with incomplete platelet recovery, defined as a platelet count below 100,000 µl. Of the 31% of patients who received a second induction cycle, 59% achieved CR. Response rates were unaffected by type of AML.
Of the 62 patients who achieved CR, 41 received at least one cycle of consolidation chemotherapy, of whom 25 received two cycles. There were no cases of dose-limiting toxicity, aside from one case of grade 3 sensory neuropathy.
Grade 4 hematologic toxicity was experienced by 96% of patients during induction, in addition to which there were 51 patients with grade 3 and three patients with grade 4 febrile neutropenia. There were eight deaths during induction.
During consolidation, 98% of patients had grade 4 hematologic toxicity, plus 15 patients had grade 3 and one patient grade 4 febrile neutropenia, and 12 patients had grade 3 and two patients grade 4 clinically documented infections. There was one treatment-related death.
The researchers observe in the Journal of Clinical Oncology: "Strategies such as altering the route of administration of bortezomib from IV to subcutaneous, changing the schedule from twice to once per week, or using other proteasome inhibitors with less neurotoxicity, such as carfilzomib, may reduce neurotoxicity without sacrificing clinical efficacy; these approaches warrant investigation in future clinical studies."
Median follow up for 34 surviving patients was 22 months. Median disease-free survival was 8 months, while medial overall survival was 12 months.
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