Liu Wenshuai, Jiang Quan, Zhou Yuhong
Department of General Surgery, Shanghai Public Health Clinical Center, Zhongshan Hospital (South Branch), Fudan University, Shanghai 200032, China.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Chin Clin Oncol. 2018 Aug;7(4):42. doi: 10.21037/cco.2018.08.02.
Soft-tissue sarcoma (STS) is a group of rare but highly heterogeneous neoplasms. Systemic treatment with cytotoxic chemotherapy and targeted agents is one of the main therapeutic modalities in patients with unresectable or metastatic disease, while adjuvant and neoadjuvant chemotherapy for adult-type sarcomas remain controversial. Although an anthracycline (doxorubicin) and ifosfamide remain the cornerstone for chemotherapy, advances have been made recently to exceed its limited efficacy, other agents such as trabectedin, eribulin have been approved. In a recent study, the addition of platelet-derived growth factor receptor (PDGFR) antibody-olaratumab to doxorubicin resulted in prolongation of progression-free survival and overall survival, which really means a breakthrough for STS. There is more emerging evidence of different sensitivity to treatment for different histological subtypes, second-line treatment for advanced sarcoma is being increasingly driven by histology. Cytotoxic drugs such as dacarbazine, gemcitabine, and taxanes have shown moderate activity in specific subtypes. Tyrosine kinase inhibitors (TKIs), including pazopanib and anlotinib, appear to be the promising targeted therapies. Other signal pathway inhibitors as CDK4/CDK6 inhibitor, imatinib, mTOR inhibitors, ALK inhibitor has shown some preliminary effect that need to be verified in the future trials. Checkpoint inhibitors as anti-PD-1 and CTLA-4 monoclonal antibodies have been used as a single agent or in combination in the early clinical trials, while further research needs to focus on better patient selection and new combinational strategies. In this review, we aim to summarize the advances of chemotherapy, targeted therapy and immunotherapy in the management of STS.
软组织肉瘤（STS）是一组罕见但高度异质性的肿瘤。细胞毒性化疗和靶向药物的全身治疗是不可切除或转移性疾病患者的主要治疗方式之一，而成人型肉瘤的辅助化疗和新辅助化疗仍存在争议。尽管蒽环类药物（多柔比星）和异环磷酰胺仍然是化疗的基石，但最近已经取得了进展以超越其有限的疗效，其他药物如曲贝替定、艾日布林已获批准。在最近的一项研究中，在多柔比星中添加血小板衍生生长因子受体（PDGFR）抗体奥拉单抗可延长无进展生存期和总生存期，这对STS来说确实意味着一个突破。越来越多的证据表明不同组织学亚型对治疗的敏感性不同，晚期肉瘤的二线治疗越来越受组织学驱动。达卡巴嗪、吉西他滨和紫杉烷等细胞毒性药物在特定亚型中显示出中等活性。酪氨酸激酶抑制剂（TKIs），包括帕唑帕尼和安罗替尼，似乎是有前景的靶向治疗方法。其他信号通路抑制剂如CDK4/CDK6抑制剂、伊马替尼、mTOR抑制剂、ALK抑制剂已显示出一些初步效果，需要在未来试验中进行验证。检查点抑制剂如抗PD-1和CTLA-4单克隆抗体已在早期临床试验中作为单药或联合使用，而进一步的研究需要专注于更好的患者选择和新的联合策略。在本综述中，我们旨在总结化疗、靶向治疗和免疫治疗在STS管理中的进展。
