Aldoxorubicin for the treatment of advanced soft tissue sarcoma

Introduction: Soft tissue sarcomas (STS) comprise a group of uncommon mesenchymal tumors of heterogeneous differentiation. For advanced STS, single-agent doxorubicin or doxorubicin-based combinations are commonly used, but at serious risk of cumulative cardiotoxicity. In addition, doxorubicin is the sheet anchor drug for many malignancies, both solid and hematologic. Areas covered: Aldoxorubicin, a doxorubicin prodrug currently in development, was designed to bind covalently to serum albumin and remains conjugated until transported to an acidic environment, such as the tumor site. We review the novel mechanism of action and the published pharmacokinetic, safety and efficacy data from Phase I, Ib/II and II clinical studies of aldoxorubicin in patients with advanced solid tumors, including advanced STS. Expert opinion: Chemical modification of doxorubicin, an effective but cardiotoxic chemotherapy drug, to aldoxorubicin has yielded a notable improvement in patient outcomes. This small step in drug chemistry may provide a giant leap in the future of cancer treatment. With its improved efficacy and low incidence of acute cardiotoxicity, aldoxorubicin may supersede doxorubicin as the treatment of choice for STS and other malignancies.