Aldoxorubicin: a tumor-targeted doxorubicin conjugate for relapsed or refractory soft tissue sarcomas.
Aldoxorubicin: a tumor-targeted doxorubicin conjugate for relapsed or refractory soft tissue sarcomas.
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DOI：
10.2147/dddt.s140638
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Hendifar A
中科院分区：
文献类型：
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作者：
Gong J;Yan J;Forscher C;Hendifar A
尽管最初的全身治疗后可用的治疗，预后仍然很差，复发性或难治性软组织肉瘤（STS）。迫切需要合理和临床开发新药，以改善这一高度未满足需求领域的结局。Aldoxorubicin是多柔比星的前药，其在给药后立即通过酸敏感性腙接头与血清白蛋白结合，随后转运至肿瘤组织，在肿瘤组织中酸性环境切割接头并促进肿瘤靶向药物有效载荷的递送。在迄今为止的临床研究中，已有证据表明其有效性和减轻的心脏毒性。在这篇综述中，我们全面详细介绍了aldoxorubicin在STS的临床发展。特别是，我们强调了在晚期或转移性STS中I期、II期和III期试验的药代动力学和疗效的可用数据。最后，我们考虑未来的研究方向，这种有前途的抗肿瘤药物。
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.