Xie Lu, Ji Tao, Guo Wei
Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing 100044, P.R. China.
Oncol Rep. 2017 Aug;38(2):625-636. doi: 10.3892/or.2017.5735. Epub 2017 Jun 21.
Osteosarcomas (OS), especially those with metastatic or unresectable disease, have limited treatment options. The greatest advancement in treatments occurred in the 1980s when multi-agent chemotherapy, including doxorubicin, cisplatin, high-dose methotrexate, and, in some regimens, ifosfamide, was demonstrated to improve overall survival compared with surgery alone. However, standard chemotherapeutic options have been limited by poor response rates in patients with relapsed or advanced cases. It has been reported that VEGFR expression correlates with the outcome of patients with osteosarcoma and circulating VEGF level has been associated with the development of lung metastasis. At present, it seems to us that progress has not been made since Grignani reported a phase II cohort trial of sorafenib and sorafenib combined with everolimus for advanced osteosarcoma, which, in a sense, have become a milestone as a second-line therapy for osteosarcoma. Although the recognization of muramyltripepetide phosphatidyl-ethanolamine has made some progress based on its combination with standard chemotherapy, its effect on refractory cases is controversial. Personalized comprehensive molecular profiling of high-risk osteosarcoma up to now has not changed the therapeutic prospect of advanced osteosarcoma significantly. Thus, how far have we moved forward and what therapeutic strategy should we prefer for anti-angiogenesis therapy? This review provides an overview of the most updated anti-angiogenesis therapy in OS and discusses some clinical options in order to maintain or even improve progression-free survival.
骨肉瘤（OS），尤其是那些伴有转移或无法切除疾病的骨肉瘤，治疗选择有限。治疗方面最大的进展发生在20世纪80年代，当时多药联合化疗，包括阿霉素、顺铂、大剂量甲氨蝶呤，以及在某些方案中使用的异环磷酰胺，被证明与单纯手术相比可提高总生存率。然而，标准的化疗选择受到复发或晚期病例患者低反应率的限制。据报道，VEGFR表达与骨肉瘤患者的预后相关，循环VEGF水平与肺转移的发生有关。目前，在我们看来，自从Grignani报道了一项索拉非尼以及索拉非尼联合依维莫司用于晚期骨肉瘤的II期队列试验以来，进展甚微，从某种意义上说，该试验已成为骨肉瘤二线治疗的一个里程碑。尽管基于其与标准化疗联合使用，对胞壁酰三肽磷脂酰乙醇胺的认识已取得一些进展，但其对难治性病例的效果仍存在争议。迄今为止，高危骨肉瘤的个性化综合分子分析并未显著改变晚期骨肉瘤的治疗前景。那么，我们在抗血管生成治疗方面取得了多大进展，应该优先选择何种治疗策略呢？本综述概述了骨肉瘤中最新的抗血管生成治疗，并讨论了一些临床选择，以维持甚至改善无进展生存期。
