2017 Volume 32 Issue 2 Pages 100-108
The standard therapy of acute myeloid leukemia is a combination of cytarabine and daunorubicin. The standard doses of these drugs are 100 - 200mg/sqm for consecutive 7 days, and 90 mg/sqm for 3 injections, respectively, against younger patients, and 100 - 200mg/sqm for consecutive 7 days, and 45 mg/sqm for 3 injections, against elderly patients. There are debates on the doses of these agents. As cytarabine has a short half time of serum level when injected subcutaneously or intravenously, continuous intravenous injection was preferentially used. Intra-cellular ara-CTP, which is an active derivative of cytarabine, which exerts as killing activity in leukemic cells, is saturated when intravenous shot of as much as 3000 mg/sqm of cytarabine, high dose ara-CTP is another standard dose utilized for consolidation or maintenance therapy. The most effective dose of daunorubicin has been determined by clinical trials comparing the dose. In younger patients, 90 mg/sqm x 3 days had longer EFS than 45 mg/sqm in patients younger than 60 years, while there was no difference among patients older than 60 years old. CPX-351 is a liposomal formulation of cytarabine:daunorubicin designed to deliver synergistic drug ratios to leukemia cells. The drug is infused over 90 minutes on days 1, 3, and 5. Phase I and II study has shown the efficacy in patients with secondary AML. Recently, a phase III data were presented in ASCO meeting 2016. The study compared CPX-351 with a combination of cytarabine and daunorubicin. The doses of these two agents were, 100 mg/sqm for consecutive 7 days, and 60 mg/sqm for three days, respectively. The phase III result showed that OS, an endpoint of this study as well as EFS, and CR rate was significantly higher in the CPX-351. Although, there is a dispute on the selectin of the control arm in the dose of cytarabine and daunorubicin, this is a remarkable result that showed better OS than standard therapy for the first time in this decade.
