Long-Term Follow-up of a Randomized Study of Oral Etoposide versus Viscum album Fermentatum Pini as Maintenance Therapy in Osteosarcoma Patients in Complete Surgical Remission after Second Relapse.

Q2 Medicine

Sarcoma Pub Date : 2020-04-26 eCollection Date: 2020-01-01 DOI:10.1155/2020/8260730

Alessandra Longhi, Marilena Cesari, Massimo Serra, Erminia Mariani

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Abstract

Background: In relapsed osteosarcoma, the 5-yr postrelapse disease-free survival (PRDFS) rate after the second relapse is <20%. In June 2007, a randomized study was started comparing oral etoposide vs Viscum album fermentatum Pini (an extract derived from the parasitic plant Viscum album L., European mistletoe) as maintenance therapy in patients with metastatic osteosarcoma in complete surgical remission after the second relapse. The primary endpoint was the PRDFS rate at 12 months (compared to the historical control rate). This is a long-term updated result. Patients and Methods. 10 patients received oral etoposide 50 mg/m² daily for 21 days every 28 days for 6 months, and 9 patients received Viscum album fermentatum Pini 3 times/wk subcutaneously for 1 year. The study closed early in July 2011 due to insufficient recruitment. Lymphocyte subpopulations were analyzed at T0, T3, T6, T9, and T12 months.

Results: On 30 June 2019, at a median follow-up ITT of 83 months (range 3-144 ms), a median PRDFS of 106 ms (2-144) was observed in the Viscum arm with 5/9 patients who never relapse vs a PRDFS of 7 months (3-134) in the etoposide arm (all patients in the Etoposide arm relapsed) (hazard ratio HR = 0.287, 95% CI: 0.076-0.884, p=0.03). Model forecast 10-yr overall survival rates as 64% in the Viscum arm and 33% in the etoposide arm. Lymphocyte subpopulation counts (CD3, CD4, and CD56) showed an increase in the Viscum arm while a decrease was observed in the etoposide arm during treatment.

Conclusions: After 12 years from the start of the trial, the patients in the Viscum arm continue to show a considerably longer PRDFS compared to oral etoposide, and a trend for an advantage in OS is evident even if the number of treated patients is too small to draw conclusions. Viscum as maintenance treatment after complete surgical remission in relapsed osteosarcoma should be further investigated and compared with other drugs.

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骨肉瘤患者第二次复发后完全手术缓解期口服依托泊甙与白花蛇舌草作为维持疗法的随机研究的长期随访。

背景：在复发的骨肉瘤患者中，将Viscum album fermentatum Pini（一种从寄生植物Viscum album L.（欧洲槲寄生）中提取的提取物）作为手术完全缓解的转移性骨肉瘤患者第二次复发后的维持疗法，可提高其复发后5年的无病生存率（PRDFS）。主要终点是12个月后的PRDFS率（与历史对照组相比）。这是一项长期更新结果。患者和方法10名患者口服依托泊苷50毫克/平方米，每天21天，每28天一次，共6个月；9名患者皮下注射白花蛇舌草，3次/周，共1年。由于招募人数不足，该研究于 2011 年 7 月提前结束。在T0、T3、T6、T9和T12个月时对淋巴细胞亚群进行了分析：2019年6月30日，中位随访ITT为83个月（范围3-144毫秒），观察到Viscum治疗组的中位PRDFS为106毫秒（2-144），其中5/9的患者从未复发，而依托泊苷治疗组的PRDFS为7个月（3-134）（依托泊苷治疗组的所有患者均复发）（危险比HR=0.287，95% CI：0.076-0.884，P=0.03）。模型预测粘杆菌素治疗组的 10 年总生存率为 64%，依托泊苷治疗组为 33%。在治疗期间，粘杆菌素治疗组的淋巴细胞亚群计数（CD3、CD4和CD56）有所上升，而依托泊苷治疗组则有所下降：在试验开始 12 年后，与口服依托泊苷相比，Viscum 治疗组患者的 PRDFS 持续时间更长，而且 OS 优势的趋势也很明显，尽管接受治疗的患者人数太少而无法得出结论。Viscum作为复发性骨肉瘤手术完全缓解后的维持治疗药物，应进一步研究并与其他药物进行比较。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Sarcoma Medicine-Radiology, Nuclear Medicine and Imaging

CiteScore

5.00

自引率

0.00%

发文量

审稿时长

14 weeks

期刊介绍： Sarcoma is dedicated to publishing papers covering all aspects of connective tissue oncology research. It brings together work from scientists and clinicians carrying out a broad range of research in this field, including the basic sciences, molecular biology and pathology and the clinical sciences of epidemiology, surgery, radiotherapy and chemotherapy. High-quality papers concerning the entire range of bone and soft tissue sarcomas in both adults and children, including Kaposi"s sarcoma, are published as well as preclinical and animal studies. This journal provides a central forum for the description of advances in diagnosis, assessment and treatment of this rarely seen, but often mismanaged, group of patients.