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Invited Commentary
December 2015

Aldoxorubicin in Sarcoma: Teaching an Old Drug New Tricks

Author Affiliations
  • 1Division of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor

Copyright 2015 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Oncol. 2015;1(9):1280-1281. doi:10.1001/jamaoncol.2015.3221

Improving the outcomes of patients with sarcoma has been stunted by the dearth of effective drugs in this diverse group of cancers. Some progress has been made over the past 2 decades in identifying new agents with activity in specific sarcomas, such as imatinib mesylate in gastrointestinal stromal tumor and dermatofibrosarcoma protuberans, trabectedin and eribulin mesylate in liposarcoma and leiomyosarcoma, paclitaxel in angiosarcoma, and gemcitabine hydrochloride combinations and pazopanib hydrochloride in soft-tissue sarcomas. Nonetheless, doxorubicin hydrochloride and ifosfamide remain the most active agents across a broad array of sarcoma subtypes. Both cytotoxics yield relatively low single-agent objective response rates approximating 15% and are associated with substantial toxicity. Although the hunt for novel agents with activity in sarcoma continues, increasingly, antineoplastic strategies have involved redesigning the old drugs with a goal of improving the therapeutic index. This is not a new effort; epirubicin hydrochloride, mitoxantrone hydrochloride, and liposomal doxorubicin are earlier examples that were developed into commercial products. Recent efforts in sarcoma have included development of palifosfamide and evofosfamide, each of which alleviates much of the neurotoxicity, nephrotoxicity, and urothelial toxicity of ifosfamide.