BACKGROUND The role of high-dose chemotherapy in relapsing osteosarcomas has not been established. We evaluated the efficacy and tolerance of high-dose thiotepa (HDTp) after standard chemotherapy (SCT) in patients with relapsed osteosarcoma. PATIENTS AND METHODS This randomised open-label phase II study enrolled patients 1-50 years, with local or metastatic relapse of a high-grade osteosarcoma, not progressive after two cycles of SCT, for whom a complete surgery can be achievable following treatment. The trial assigned enrolled patients in a 1:1 ratio to receive two additional courses of SCT + HDTp and autologous transplantation (Arm A), or SCT alone (Arm B). Surgery for complete resection was scheduled as soon as feasible. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS) and safety. RESULTS From September 2009 to November 2016, 44 patients were randomised (A:22; B:22). In total, 54.5% were males, and the median age was 16 years (9-32years). The two-year OS rate was 66.7% (95% CI 42.5-82.5) (SCT + HDTp, Arm A) versus 50.0% (95% CI 28.2-68.4) for SCT alone (Arm B). Median OS was 27.4 and 24.8 months, respectively (hazard ratio [HR] 0.826, 95% CI 0.393-1.734; p = 0.6123). Median PFS was 15.6 (8.9-24.9) months in Arm A versus 7.2 (4.8-33.3) months in Arm B, p = 0.3845. Among the 22 patients treated with SCT + HDTp, 16 (72.7%) experienced at least one grade ≥3 adverse events versus 18/22 (81.8%) patients treated with SCT. No toxic death occurred. CONCLUSION Adjuvant HDTp failed to significantly improve OS and PFS in resectable relapsed osteosarcomas. Despite a trend of prolonged survival and an acceptable toxicity, thiotepa cannot be recommended. KEY MESSAGE HDTp and autologous transplantation added to SCT did not improve OS and PFS in patients with resectable relapsed osteosarcomas. Despite a trend of prolonged survival, thiotepa cannot be recommended.

中文翻译：

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一项多中心随机II期临床试验，评估可切除的复发性骨肉瘤患者中大剂量的thiotepa作为标准化疗的辅助治疗。

背景技术尚未确定大剂量化学疗法在复发性骨肉瘤中的作用。我们评估了标准化疗（SCT）后骨肉瘤复发患者的大剂量硫替太帕（HDTp）的疗效和耐受性。患者和方法这项随机开放标签的II期随机研究招募了1至50岁，局部或转移性高级别骨肉瘤复发的患者，在两个SCT周期后并未进展，对其进行治疗后可以完成手术。该试验以1：1的比例分配入组患者，以接受另外两个疗程的SCT + HDTp和自体移植（Arm A），或单独接受SCT（Arm B）。计划尽快进行完全切除手术。主要终点是总体生存期（OS）。次要目标包括无进展生存期（PFS）和安全性。结果从2009年9月至2016年11月，随机分配了44例患者（A：22; B：22）。男性总计54.5％，中位年龄为16岁（9-32岁）。两年的OS率为66.7％（95％CI 42.5-82.5）（SCT + HDTp，A组），而单独使用SCT（Arm B）的50.0％（95％CI 28.2-68.4）。中位OS分别为27.4和24.8个月（危险比[HR] 0.826，95％CI 0.393-1.734； p = 0.6123）。A组的PFS中位数为15.6（8.9-24.9）个月，B组的中位PFS为7.2（4.8-33.3）个月，p = 0.3845。在22名接受SCT + HDTp治疗的患者中，有16名（72.7％）经历了至少一种≥3级不良事件，而18/22（81.8％）名患者接受了SCT。没有发生中毒死亡。结论佐剂HDTp不能显着改善可切除的复发性骨肉瘤的OS和PFS。尽管有延长生存期和可接受毒性的趋势，不推荐使用thiotepa。关键信息在可切除的复发性骨肉瘤患者中，将HDTp和自体移植添加到SCT中并不能改善OS和PFS。尽管有延长生存期的趋势，但不建议使用噻替帕。