Aldoxorubicin for the treatment of soft tissue sarcoma

Expert Opin Investig Drugs. 2017 Oct;26(10):1175-1179. doi: 10.1080/13543784.2017.1371134. Epub 2017 Aug 28.

Abstract

Intoduction: Soft tissue sarcomas (STS) encompass a group of rare tumors arising from mesenchymal tissue. Traditionally, anthracycline-based chemotherapy, with doxorubicin, is the main treatment for advanced STS. Areas covered: Aldoxorubicin is a doxorubicin derivative containing a carboxylic hydrazone and serves as a prodrug of doxorubicin. It covalently binds to albumin in the blood until reaching the acidic tumor environment, which dissolves the hydrazone linker, thus releasing doxorubicin into the tissue. In this review paper, we analyze the pharmacokinetics, current phase I, phase II, and phase III trials, as well as adverse effect profile of aldoxorubicin in patients with advanced STS. Expert opinion: Aldoxorubicin represents a promising drug for treatment of sarcomas. The drug has minimal cardiac toxicity, which represents a significant advantage to doxorubicin. Preliminary phase 3 study results demonstrate PFS advantage in patients with leiomyosarcoma and liposarcoma. However, more studies are needed to establish the role of aldoxorubicin in sarcoma treatment.

Keywords: Albumin; DOXO-EMCH; INNO-206; aldoxorubicin; doxorubicin derivative; doxorubicinol; leiomyosarcoma; liposarcoma; soft tissue sarcoma.

Publication types

  • Review

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacokinetics
  • Drug Design
  • Humans
  • Hydrazones / administration & dosage*
  • Hydrazones / adverse effects
  • Hydrazones / pharmacokinetics
  • Sarcoma / drug therapy*
  • Sarcoma / pathology
  • Tissue Distribution

Substances

  • Antibiotics, Antineoplastic
  • Hydrazones
  • Doxorubicin
  • DOXO-EMCH