Clinical activity of mTOR inhibition in combination with cyclophosphamide in the treatment of recurrent unresectable chondrosarcomas
Clinical activity of mTOR inhibition in combination with cyclophosphamide in the treatment of recurrent unresectable chondrosarcomas
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DOI：
10.1007/s00280-012-1968-x
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发表时间：
2012-12-01
影响因子：
3
通讯作者：
Merimsky, Ofer
中科院分区：
文献类型：
--
作者：
Bernstein-Molho, Rinat;Kollender, Yehuda;Merimsky, Ofer
软骨肉瘤（CS）是一组异质性的罕见肉瘤，对化疗或放疗反应不良。当复发性或转移性疾病的局部治疗用尽时，化疗起着边缘作用。不同的分子途径已被证明在CS中被激活。在这项回顾性研究中，我们总结了使用西罗莫司（SIR）和环磷酰胺（CTX）联合治疗一组复发性不可切除CS患者的经验。2007年至2012年期间，连续10例不可切除CS患者接受了SIR和CTX的超说明书治疗。分析肿瘤反应、无进展生存期（PFS）、不良事件和其他相关临床数据。患者年龄中位数为49岁（范围28-68岁）。自初步诊断以来的中位无病期为22.5个月。由于额外的局部手术治疗、转移瘤切除或缓慢的无症状进展，从疾病复发到开始SIR和CTX治疗的中位时间为21.7个月。观察到1例（10%）客观缓解，6例（60%）患者病情稳定至少6个月。3例患者出现疾病进展。中位PFS为13.4个月（范围3-30.3）。虽然晚期CS仍然是一种无法治愈的疾病，但我们的经验表明SIR和CTX的组合耐受性良好，并且可能具有有意义的临床活性，疾病控制率为70%。进一步的前瞻性研究是必要的。
Chondrosarcomas (CS) represent a heterogeneous group of rare sarcomas, poorly responsive to chemotherapy or radiotherapy. When local therapies in recurrent or metastatic disease are exhausted, chemotherapy plays a marginal role. Different molecular pathways have been shown to be activated in CS. In this retrospective study, we summarize our experience in treating a cohort of patients with recurrent unresectable CS with a combination of sirolimus (SIR) and cyclophosphamide (CTX).Ten consecutive patients with unresectable CS were offered off-label treatment with SIR and CTX between 2007 and 2012. Tumor response, progression-free survival (PFS), adverse events, and other relevant clinical data were analyzed.The median patients' age was 49 (range 28-68). Median disease-free interval since the primary diagnosis was 22.5 months. Median time from the disease recurrence to initiation of SIR and CTX treatment was 21.7 months due to additional local surgical treatments, excision of metastases, or slow asymptomatic progression. One (10 %) objective response was observed, and six (60 %) patients had stabilization of disease for at least 6 months. Three patients had progressive disease. Median PFS was 13.4 months (range 3-30.3). No significant adverse events were observed.Although advanced CS remains an incurable disease, our experience suggests that a combination of SIR and CTX is well tolerated and may have meaningful clinical activity with disease control rate of 70 %. Further prospective studies are warranted.