Adding Oral Pioglitazone to Standard Induction Chemotherapy of Acute Myeloid Leukemia: A Randomized Clinical Trial

Abstract Background The hypothesis of an effect by thiazolidinedione on leukemia cells was proposed 2 decades ago, but there is little clinical evidence regarding its efficacy. We evaluated the safety and efficacy of adding pioglitazone to standard induction chemotherapy in patients with acute myeloid leukemia (AML). Patients and Methods In this randomized clinical trial, newly diagnosed AML patients were randomized to 1 of 2 groups. Patients in both groups received cytarabine (100 mg/m 2 per day for 7 days) and daunorubicin (60 mg/m 2 per day for 3 days). Patients in the pioglitazone group additionally received oral pioglitazone (45 mg per day). The 2 groups were compared according to remission rate, laboratory findings, and adverse events during treatment. Results Forty patients were evaluated, 20 patients in each group. The complete remission rate was 20% more in the pioglitazone group compared to the control group ( P  = .202). Complications due to pioglitazone discontinuation were observed in 2 cases. The mean serum alanine aminotransferase in the fourth treatment week was significantly more in pioglitazone group compared to the control group (65.5 vs. 33.6 mg/dL, P  = .039). The mean serum creatinine in all treatment phases was significantly higher in the pioglitazone group compared to the control group ( P P > .05). Conclusion Adding pioglitazone to cytarabine and daunorubicin increased the remission rate in AML patients compared to control subjects. Although this difference in remission rate between the 2 groups was not statistically significant, it could be important in the clinical setting. Pioglitazone may provide benefits as an adjuvant therapy for AML patients without causing serious adverse events.