Pediatric Hematology/Oncology, Department of Pediatrics, University Hospital Tuebingen, Tuebingen, Germany.
Clinic for Anaesthesiology, Critical Care, Emergency Medicine and Pain Management, Klinikum Ludwigsburg, Germany.
Pediatr Hematol Oncol. 2021 Aug;38(5):471-485. doi: 10.1080/08880018.2021.1872748. Epub 2021 Feb 26.
Arsenic trioxide (ATO) has become an established component of treatment protocols for acute promyelocytic leukemia (APL) with excellent efficacy and no relevant sustained toxicity. Part of its action has been attributed to the inhibition of Hedgehog signaling (Hh) which enables a possible therapeutic approach as many pediatric tumor entities have been associated with increased Hh activity. We retrospectively analyzed 31 patients with refractory and relapsed pediatric cancer who were treated with ATO at the University Children's Hospital of Tuebingen. Additionally a literature review on the clinical and preclinical use of ATO in pediatric cancer treatment was performed.ATO alone as well as combinations with other drugs have proven effective and in mouse models of various pediatric malignancies. However, only few data on the clinical use of ATO in pediatric patients besides APL exist. In our patient sample, ATO was overall well tolerated in the treatment of various pediatric cancers, even in combination with other cytostatic drugs. Due to distinct tumor entities, differently progressed disease stages and varying co-medication, no clear statement can be made regarding the efficacy of ATO treatment. However, patients with proven Hh activation in molecular tumor profiling surpassed all other patients, who received ATO in an experimental treatment setting, in terms of survival. As molecular profiling of tumors increases and enhanced Hh activity can be detected at an early stage, ATO might expand its clinical use to other pediatric malignancies beyond APL depending on further clinical studies.
三氧化二砷（ATO）已成为急性早幼粒细胞白血病（APL）治疗方案的重要组成部分，具有良好的疗效且无相关持续毒性。其部分作用归因于 Hedgehog 信号通路（Hh）的抑制，这为治疗提供了一种可能的方法，因为许多儿科肿瘤实体与 Hh 活性增加有关。我们回顾性分析了在图宾根大学儿童医院接受 ATO 治疗的 31 例难治性和复发性儿科癌症患者。此外，还对 ATO 在儿科癌症治疗中的临床和临床前应用进行了文献综述。ATO 单独使用以及与其他药物联合使用已被证明在各种儿科恶性肿瘤的治疗中有效，并且在各种儿科恶性肿瘤的小鼠模型中也有效。然而，除了 APL 之外，关于 ATO 在儿科患者中的临床应用的数据很少。在我们的患者样本中，ATO 在治疗各种儿科癌症时总体上耐受性良好，即使与其他细胞毒性药物联合使用也是如此。由于不同的肿瘤实体、不同进展阶段的疾病和不同的合并用药，因此无法对 ATO 治疗的疗效做出明确的评价。然而，在分子肿瘤分析中证实存在 Hh 激活的患者在生存方面优于所有其他接受 ATO 实验性治疗的患者。随着肿瘤的分子分析增加，并且可以在早期检测到增强的 Hh 活性，根据进一步的临床研究，ATO 可能会将其临床应用扩展到 APL 以外的其他儿科恶性肿瘤。
