Objective: The use of conventional doxorubicin in combination with trabectedin leads to a considerable prolongation of progression-free survival in the treatment of uterine sarcomas but is associated with dose-limiting toxicities. Significant progression-free survival improvement was recently obtained through treatment prolongation with trabectedin single agent. We hypothesize that the therapeutic index of pegylated liposomal doxorubicin combined with trabectedin could be superior to the combination with conventional doxorubicin due to a more favorable toxicity profile.

Methods: In this retrospective cohort study, the clinical outcome was analyzed in patients with advanced or recurrent uterine sarcomas with measurable disease treated with pegylated liposomal doxorubicin 30 mg/m² plus trabectedin 1.5 mg/m² given every 3 weeks between January 2011 and April 2023 at the University Hospital in Innsbruck. Response evaluation was done every three cycles. Toxicity was evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria on 107 administered cycles.

Results: A total of 21 patients were included in the study. In 67% (n=14) of patients, pegylated liposomal doxorubicin plus trabectedin was given as first-line treatment. One patient (5%) achieved a complete response and four (19%) a partial response, resulting in an objective response rate of 24%. Four other patients (19%) had stable disease. The median duration of the response was 14 months (range 3-74). Progression was recorded in 12 patients (57%). Median progression-free survival was 6 months (95% CI 1 to 11 months), while median overall survival was 26 months (95% CI 9 to 43 months). A median of 6 (range 1-11) cycles per patient were administered. Regarding grade ≥3 toxicity, neutropenia was recorded in 29%, thrombocytopenia in 14%, and febrile neutropenia in 19% of patients. Hematologic toxicity was the most frequent reason for dose delays (n=16) and dose reductions (n=5).

Conclusion: Our study found an overall clinical benefit for the combination of pegylated liposomal doxorubicin plus trabectedin in metastatic uterine sarcomas of 43% and appears to exhibit a favorable toxicity profile which allows prolonged administration of this regimen.

Keywords: Gynecology; Sarcoma.

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目标： 传统多柔比星与曲贝替丁联合使用可显著延长子宫肉瘤患者无进展生存期，但会导致剂量限制性毒性。最近通过单药长期应用曲贝替丁获得了明显的无进展生存改善。我们假设，在治疗中使用聚乙二醇化脂质体多柔比星与曲贝替丁的组合相比传统的多柔比星可能具有更优的治疗指数，这得益于其更有利于患者的毒副反应谱。

方法： 在这项回顾性队列研究中，研究人员分析了2011年1月至2023年4月期间在因斯布鲁克大学医院接受聚乙二醇化脂质体多柔比星（剂量为30 mg/m²）加曲贝替丁（剂量为1.5 mg/m²），每三周一次治疗的晚期或复发性子宫肉瘤患者的临床结果。患者疾病可测量的情况下进行评估，每个周期后对疗效进行评价，并根据国家癌症研究所(NCI)通用术语标准，在107个给药周期中对毒副反应进行评定。

结果： 本研究共纳入21名患者。在67%（n=14）的患者中，聚乙二醇化脂质体多柔比星加曲贝替丁被用作一线治疗方案。一名患者（5%）达到完全缓解，四名（19%）患者部分缓解，总客观缓解率为24%。另外四名患者（19%）疾病稳定。中位反应持续时间为14个月（范围3-74）。在12名患者（57%）中记录了进展。无进展生存期的中位数为6个月（95% CI 1至11个月），而总生存期的中位数为26个月（95% CI 9到43个月）。每位患者的平均治疗周期为6次（范围1-11）。在≥3级毒性方面，中性粒细胞减少占29%，血小板减少占14%，发热性中性粒细胞减少占19%。血液学毒副反应是最常见的延迟给药和减量原因。

结论： 我们的研究发现，在转移性子宫肉瘤患者中，聚乙二醇化脂质体多柔比星加曲贝替丁的组合总体上具有临床益处（43%），并且似乎展现出有利于长期治疗的毒副反应谱。

关键词： 妇科；肉瘤。