Neiman Zachary M, Legasto Carlo S, Chin Alan K, Guan Tiffany, Schulte Brian C
School of Medicine, University of California San Francisco, San Francisco, CA, United States.
Department of Pharmaceutical Services, University of California San Francisco, San Francisco, CA, United States.
Front Oncol. 2025 Jul 16;15:1621409. doi: 10.3389/fonc.2025.1621409. eCollection 2025.
Dexrazoxane (DZR) has been used to prevent cardiotoxicity from doxorubicin (DOX), particularly in younger patients with cancer and those with pre-existing cardiac dysfunction. Herein, we sought to further define the role of DZR by evaluating its capacity to mitigate cardiotoxicity in patients actively receiving DOX, while also assessing concomitant toxicities.
We conducted a retrospective, propensity-matched cohort study at a single academic center, comparing outcomes between patients treated with DZR plus DOX and those who received DOX alone. Patients were matched by age, sex, and cumulative lifetime dose of DOX. Cardiotoxicity was assessed as the change in ejection fraction (EF) during and after treatment. To evaluate associations between DZR and other toxicities, we utilized the Common Terminology Criteria for Adverse Events, Version 5 (CTCAE).
A total of 152 patients were included across both groups. The DOX alone and DOX + DZR groups had median ages of 36 and 28 (ranges 18-68 and 18-69), with median cumulative DOX doses of 375 mg/m (ranges 75-525 and 75-600), respectively. Patients were followed up with their last measured EF at a median of -3 and 18.5 days after their final DOX dose, respectively. The median change in EF was -2% in the DOX alone group and -0.7% in the DOX + DZR group (p = 0.9174). Grade 4 anemia occurred in 16 patients in the DOX alone group and in 41 patients in the DOX + DZR group (p = 0.0002). Similarly, grade 4 neutropenia was observed in 15 and 50 patients, respectively (p = 0.0013).
The addition of DZR to DOX did not result in a statistically significant change in EF during the treatment window. Given the limitations of the dataset, this may suggest a lack of substantial immediate benefit from the co-administration of DZR with DOX. An increased rate of high-grade neutropenia and anemia was observed in patients receiving the combination, although this may be due to confounding factors. Further analysis is warranted, ideally through larger multi-institutional or prospective studies.
右丙亚胺（DZR）已被用于预防阿霉素（DOX）引起的心脏毒性，特别是在年轻癌症患者和已有心脏功能障碍的患者中。在此，我们试图通过评估其减轻正在接受DOX治疗患者心脏毒性的能力，并同时评估伴随毒性，来进一步明确DZR的作用。
我们在一个学术中心进行了一项回顾性、倾向评分匹配队列研究，比较接受DZR加DOX治疗的患者与仅接受DOX治疗的患者的结局。根据年龄、性别和DOX的累积终身剂量对患者进行匹配。将治疗期间和治疗后的射血分数（EF）变化作为心脏毒性的评估指标。为了评估DZR与其他毒性之间的关联，我们采用了《不良事件通用术语标准》第5版（CTCAE）。
两组共纳入152例患者。仅接受DOX治疗组和DOX + DZR组的中位年龄分别为36岁和28岁（范围分别为18 - 68岁和18 - 69岁），DOX的中位累积剂量分别为375 mg/m（范围分别为75 - 525和75 - 600）。患者在最后一次DOX剂量后的中位-3天和18.5天分别进行最后一次EF测量随访。仅接受DOX治疗组的EF中位变化为-2%，DOX + DZR组为-0.7%（p = 0.9174）。仅接受DOX治疗组有16例患者发生4级贫血，DOX + DZR组有41例患者发生4级贫血（p = 0.0002）。同样，分别有15例和50例患者观察到4级中性粒细胞减少（p = 0.0013）。
在治疗期间，DOX联合使用DZR并未导致EF出现统计学上的显著变化。鉴于数据集的局限性，这可能表明DOX与DZR联合使用缺乏显著的即时益处。接受联合治疗的患者中观察到高级别中性粒细胞减少和贫血的发生率增加，尽管这可能是由于混杂因素所致。需要进一步分析，理想情况下通过更大规模的多机构或前瞻性研究进行。
