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Aldoxorubicin: a tumor-targeted doxorubicin conjugate for relapsed or refractory soft tissue sarcomas

Authors Gong J, Yan J, Forscher C, Hendifar A

Received 22 November 2017

Accepted for publication 12 March 2018

Published 6 April 2018 Volume 2018:12 Pages 777—786

DOI https://doi.org/10.2147/DDDT.S140638

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Sukesh Voruganti


Jun Gong,1,* Jessica Yan,2,* Charles Forscher,3 Andrew Hendifar4

1Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA; 2Department of Hematology and Oncology, Harbor-UCLA Medical Center, Torrance, CA, USA; 3Sarcoma Program, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 4Gastrointestinal and Neuroendocrine Malignancies, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA

*These authors contributed equally to this work

Abstract: Despite available therapies after initial systemic therapy, prognosis remains poor in relapsed or refractory soft tissue sarcomas (STS). The rational and clinical development of novel agents to improve outcomes in this area of high unmet need is desperately warranted. Aldoxorubicin is a prodrug of doxorubicin that binds to serum albumin immediately after administration through an acid-sensitive hydrazone linker and is subsequently transported to tumor tissues where the acidic environment cleaves the linker and facilitates delivery of a tumor-targeted drug payload. In clinical studies to date, there has been evidence of efficacy and mitigated cardiac toxicity. In this review, we comprehensively detail the clinical development of aldoxorubicin in STS to date. Specifically, we highlight available data on the pharmacokinetics and efficacy from Phase I, Phase II, and Phase III trials in advanced or metastatic STS. We conclude with considerations for future directions of investigation for this promising antitumor agent.

Keywords: aldoxorubicin, albumin conjugate, soft tissue sarcomas, clinical trials, pharmacokinetics, cardiotoxicity
 

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