ABSTRACT
Introduction: Liposarcomas (LPS) are a heterogeneous group of adipocytic soft tissue sarcomas with limited treatment options in the advanced/metastatic setting. Pazopanib is a multi-target tyrosine kinase inhibitor (TKI) with anti-angiogenic and antitumorigenic properties. Whilst targeted agents including TKIs have been extensively studied in other solid tumors and the sarcoma subtype gastrointestinal stromal tumor (GIST), we currently lack effective treatments for the liposarcoma subtype. Several phase II and III studies of oral TKIs in soft tissue sarcomas have excluded liposarcoma because of a reported lack of activity following the EORTC 62043 study. Areas: We review the use of pazopanib in advanced intermediate and high-grade liposarcomas where complete surgical resection is not possible. Expert opinion: The current clinical and pharmacological data demonstrate the efficacy of pazopanib in soft tissue sarcomas, but new data suggest that anti-angiogenic agents may have limited activity in liposarcoma. Anti-angiogenic TKIs are generally well tolerated and liposarcomas vary in their response to systemic chemotherapy; hence, there is a role for further exploration of the efficacy of this treatment amongst the histological subtypes of liposarcoma. This affords further understanding of biomarkers which may be associated with response to pazopanib and other anti-angiogenic TKI treatments.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Liposarcoma/drug therapy , Pyrimidines/therapeutic use , Sulfonamides/therapeutic use , Angiogenesis Inhibitors/pharmacology , Animals , Biomarkers, Tumor/metabolism , Humans , Indazoles , Liposarcoma/pathology , Neoplasm Grading , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/pharmacology , Sulfonamides/pharmacology , Treatment OutcomeABSTRACT
Aldoxorubicin is a prodrug formulation of doxorubicin currently under investigation for the treatment of soft tissue sarcomas. Early studies have demonstrated a promising reduction in the cardiotoxicity of aldoxorubicin compared with equivalent doses of doxorubicin leading to an increase in the equivalent cumulative dose of aldoxorubicin. The current clinical and pharmacological data available for aldoxorubicin are extremely promising for its use in the treatment of advanced and metastatic soft tissue sarcomas compared with equivalent doses of doxorubicin although Phase III data are lacking. We review aldoxorubicin for the treatment of advanced and metastatic soft tissue sarcomas and discuss the impact it may have in the future.
