Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Nursing Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Medicine (Baltimore). 2023 Aug 18;102(33):e34902. doi: 10.1097/MD.0000000000034902.
Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess the benefits and risks of NFO monotherapy or in combination with doxorubicin (DOX) versus single-drug DOX in previously untreated patients with advanced soft-tissue sarcoma (ASTS).
Online PubMed, Web of Science, Embase, and Cochrane CENTRAL databases were systematically searched on April 26, 2022. Objective response rate and disease control rate were primary outcomes. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events were secondary outcomes.
In all, 3 randomized clinical trials with a total of 1207 ASTS patients were eligible. DOX plus NFO combination therapy showed higher risk ratios of objective response rate (1.50, 95% CI 1.20-1.68, P = .0003) and disease control rate (1.15, 95% CI 1.05-1.27, P = .0030) compared with DOX monotherapy. Nevertheless, NFO-based monotherapy and combination therapy were found no improvements on OS (hazard ratio 0.93, 95% CI 0.52-1.65, P = .8050) and PFS (hazard ratio 0.88, 95% CI 0.54-1.43, P = .6088) against DOX. More incidences of grade 3 or worse anemia, thrombocytopenia, stomatitis, diarrhea, constipation, and febrile neutropenia were observed in NFO-based treatments.
Adding NFO to DOX as first-line therapy improved the responses in ASTS patients but did not prolong OS and PFS. Grade 3 or worse treatment-related adverse events should be treated with caution during the NFO-based therapies.
新型膦酰胺类化合物（NFOs）属于异环磷酰胺的活性代谢物，可绕过有毒副产物的产生。在这项分析中，我们旨在全面评估 NFO 单药或联合多柔比星（DOX）与单药 DOX 治疗未经治疗的晚期软组织肉瘤（ASTS）患者的获益和风险。
我们于 2022 年 4 月 26 日系统地检索了在线 PubMed、Web of Science、Embase 和 Cochrane CENTRAL 数据库。主要结局为客观缓解率和疾病控制率。次要结局为总生存期（OS）、无进展生存期（PFS）和≥3 级治疗相关不良事件。
共有 3 项随机临床试验，共纳入 1207 例 ASTS 患者，符合纳入标准。与 DOX 单药治疗相比，DOX 联合 NFO 治疗方案的客观缓解率（1.50，95%CI 1.20-1.68，P=.0003）和疾病控制率（1.15，95%CI 1.05-1.27，P=.0030）的风险比更高。然而，NFO 单药和联合治疗方案在 OS（风险比 0.93，95%CI 0.52-1.65，P=.8050）和 PFS（风险比 0.88，95%CI 0.54-1.43，P=.6088）方面未显示出改善。NFO 治疗方案中更常见 3 级或更高级别的贫血、血小板减少、黏膜炎、腹泻、便秘和发热性中性粒细胞减少症。
将 NFO 联合 DOX 作为一线治疗可改善 ASTS 患者的缓解率，但不能延长 OS 和 PFS。在 NFO 治疗中应谨慎处理 3 级或更高级别的治疗相关不良事件。
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