Single-Center Experience with Ifosfamide Monotherapy as Second-Line Treatment of Recurrent/Metastatic Osteosarcoma
Single-Center Experience with Ifosfamide Monotherapy as Second-Line Treatment of Recurrent/Metastatic Osteosarcoma
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DOI：
10.1634/theoncologist.2019-0528
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发表时间：
2019-12-19
期刊：
影响因子：
5.8
通讯作者：
Gelderblom, Hans
中科院分区：
文献类型：
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作者：
Verschoor, Arie Jan;Speetjens, Frank M.;Gelderblom, Hans
背景 二线姑息化疗对复发/转移性骨肉瘤患者的有效性尚不明确。几项小型研究（6-19 名患者）报告了异环磷酰胺作为二线治疗。在这项研究中，我们报告了我们在复发/转移性骨肉瘤患者中使用二线异环磷酰胺单一疗法的单中心经验。方法对1978年至2017年期间接受异环磷酰胺治疗的所有骨肉瘤患者进行图表回顾。1997年之前使用5 g/m(2)方案，从1997年起使用9 g/m(2)方案。从开始使用异环磷酰胺起的总生存期 (OS) 是主要终点。还研究了从治疗开始起的无进展生存期（PFS）。为了评估组间生存率的差异，应用了对数秩检验。为了研究异环磷酰胺剂量和世界卫生组织体能状态 (PS) 的影响，我们对 Cox 比例风险回归模型进行了估计。结果 62例复发/转移性骨肉瘤患者接受二线异环磷酰胺单药治疗（剂量5 g/m(2)，n = 26；9 g/m(2)，n = 36）。在单变量分析中，9 g/m(2) 的 OS 明显优于 5 g/m(2)（分别为 10.9 个月 [95% 置信区间 (CI), 9.3-12.6] 与 6.7 个月 [95% CI, 5.9-7.6]）和 PS（中位 OS PS 0、13.0 个月 [95% CI, 2.3-23.8]；PS 1, 8.2 个月 [95% CI，5.4-11.1]；PS >= 2，6.2 个月 [95% CI，2.2-10.3]；未知 PS，5.4 个月 [95% CI，2.2-8.5]）。在多变量分析中，仅 PS 显示出显着差异。 5 和 9 g/m(2) 异环磷酰胺治疗或 PS 之间未发现 PFS 存在差异。结论 本研究表明异环磷酰胺是复发/转移性骨肉瘤患者的有效二线治疗方法。实践意义 异环磷酰胺单一疗法通常用作骨肉瘤的二线治疗，尽管缺乏支持这一点的大系列研究。这项回顾性研究报告了 5 g/m(2) 和 9 g/m(2) 治疗方案的总体生存率和无进展生存率。这项研究无法显示 5 和 9 g/m(2) 之间的生存率存在显着差异，但显示了世界卫生组织的表现状态对总体生存率的重要影响。该研究为与正在开展的多个 II 期研究进行比较设定了标准和参考。
Background The effectiveness of second-line palliative chemotherapy in patients with recurrent/metastatic osteosarcoma is not well defined. Several small studies (6-19 patients) have reported on ifosfamide as second-line treatment. In this study we report our single-center experience with second-line ifosfamide monotherapy in patients treated for recurrent/metastatic osteosarcoma. Methods A chart review was conducted of all patients with osteosarcoma treated with ifosfamide from 1978 until 2017. Until 1997 a 5 g/m(2) regimen was used, and from 1997 onwards a 9 g/m(2) regimen was used. Overall survival (OS) from start of ifosfamide was the primary endpoint. Progression-free survival (PFS) from start of treatment was also studied. To assess difference in survival between groups the log rank test was applied. To investigate the effect of ifosfamide dose and World Health Organization performance status (PS) a Cox proportional hazard regression model was estimated. Results Sixty-two patients were selected with recurrent/metastatic osteosarcoma treated with second-line ifosfamide monotherapy (dose of 5 g/m(2), n = 26; 9 g/m(2), n = 36). OS was significantly better in univariate analysis for 9 g/m(2) compared with 5 g/m(2) (10.9 months [95% confidence interval (CI), 9.3-12.6] vs. 6.7 months [95% CI, 5.9-7.6], respectively) and for PS (median OS PS 0, 13.0 months [95% CI, 2.3-23.8]; PS 1, 8.2 months [95% CI, 5.4-11.1]; PS >= 2, 6.2 months [95% CI, 2.2-10.3]; and unknown PS, 5.4 months [95% CI, 2.2-8.5]). In multivariate analysis only PS showed a significant difference. No difference in PFS was found between 5 and 9 g/m(2) ifosfamide treatment or PS. Conclusion This study suggests that ifosfamide is an effective second-line treatment for patients with recurrent/metastatic osteosarcoma. Implications for Practice Ifosfamide monotherapy is commonly used as second-line treatment in osteosarcoma, although large series to support this are lacking. This retrospective study reports overall and progression-free survival for regimens with 5 g/m(2) and with 9 g/m(2). This study was unable to show a significant difference in survival between 5 and 9 g/m(2) but showed an important impact of World Health Organization performance status on overall survival. This study sets a standard and reference for comparison with the multiple phase II studies under development.