CPX-351 in acute myeloid leukemia: can a new formulation maximize the efficacy of old compounds?

Expert Rev Hematol. 2017 Oct;10(10):853-862. doi: 10.1080/17474086.2017.1369400. Epub 2017 Aug 24.

Abstract

The management of Acute Myeloid Leukemia (AML) (with the exception of acute promyelocytic leukemia) has remained largely unchanged over the past 40 years. In particular, patients defined as high-risk, according to the 2017 European Leukemia Net recommendations, represent a subgroup with poor response to current therapies that are frequently associated with high-grade toxicity and potentially fatal complications. Areas covered: Preliminary results from an ongoing phase III clinical trial suggest that CPX-351 could represent an interesting treatment option in both induction and 'bridge-to-transplant' settings. In particular, 60- to 75-year-old patients with secondary AML, when treated with CPX-351, exhibit superior overall survival (HR = 0.69; P = 0.005; median OS 9.56 vs. 5.95 months), event free survival (HR = 0.74; P = 0.021), and composite response rate (47.7% vs. 33.3%; P = 0.016) as compared to standard '7 + 3' therapy. Herein, we detail the main pharmacological features of CPX-351 and review updated results of clinical trials investigating its employment in AML. Expert commentary: Novel liposome-based drugs display a high therapeutic index and represent a promising alternative to unencapsulated drugs, especially when high-risk features complicate the use of standard treatments. Further efforts in both understanding AML biology and improving nanodrug design are needed.

Keywords: Acute myeloid leukemia; CPX-351; cytarabine; daunorubicin; drug delivery; liposome; nanomedicine; nanoparticles.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Drug Compounding
  • Drug Discovery
  • Drug Evaluation, Preclinical
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Liposomes
  • Nanomedicine
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Liposomes