Sheel Ankur, Bae Junu, Asada Ashlee, Otterson Gregory A, Baliga Ragavendra R, Koenig Kristin L
Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Cardiooncology. 2023 Jan 18;9(1):4. doi: 10.1186/s40959-023-00153-6.
Hypomethylating agents (HMAs) have shown efficacy in the treatment of hematological malignancies and are indicated for the treatment of chronic myelomonocytic leukemia (CMML). While the HMA decitabine, in its intravenous formulation, has been used since 2006 for the treatment of CMML, use of its oral formulation has been limited by poor bioavailability due to first-pass metabolism by the enzyme cytidine deaminase. The dose of intravenous decitabine is limited by toxicities such as cardiomyopathy and heart failure. Therefore, cedazuridine was developed as an inhibitor of cytidine deaminase. Cedazuridine decreases the first-pass metabolism of oral decitabine allowing therapeutic levels to be achieved at lower doses, and thus, the novel oral combination of cedazuridine with decitabine was developed. While cardiomyopathy and heart failure are well-established adverse effects associated with intravenous decitabine alone, there to our knowledge there have been no documented incidences of reversible cardiomyopathy in the literature or in patients who participated in the phase 2 and phase 3 clinical trials of oral decitabine-cedazuridine.
This case study presents an 85 year-old Caucasian female with CMML who developed cardiomyopathy and heart failure with reduced ejection fraction after completing 5 cycles of therapy with decitabine/cedazuridine. Furthermore, her symptoms and cardiac function recovered upon discontinuation of the drug.
We present an occurrence of reversible cardiomyopathy in a patient who completed 5 cycles of decitabine/cedazuridine, an oral combination therapy developed to enhance oral bioavailability of decitabine thereby limiting its adverse effects. As the decitabine/cedazuridine combination therapy rises in popularity due to its convenient oral formulation, more trials are needed to understand the prevalence of cardiomyopathy with this drug and to discover preventative strategies for cardiotoxic effects.
去甲基化药物（HMAs）已显示出对血液系统恶性肿瘤的治疗效果，并被用于治疗慢性粒单核细胞白血病（CMML）。自2006年以来，静脉注射用的去甲基化药物地西他滨一直用于治疗CMML，但其口服制剂因胞苷脱氨酶的首过代谢导致生物利用度差而使用受限。静脉注射地西他滨的剂量受到心肌病和心力衰竭等毒性的限制。因此，开发了西扎珠苷作为胞苷脱氨酶抑制剂。西扎珠苷可减少口服地西他滨的首过代谢，使较低剂量就能达到治疗水平，从而开发出西扎珠苷与地西他滨的新型口服组合制剂。虽然心肌病和心力衰竭是单独使用静脉注射地西他滨时公认的不良反应，但据我们所知，文献中或参与口服地西他滨 - 西扎珠苷2期和3期临床试验的患者中均未记录到可逆性心肌病的发生率。
本病例研究介绍了一名85岁的患有CMML的白种女性，她在完成5个周期的地西他滨/西扎珠苷治疗后出现了心肌病和射血分数降低的心力衰竭。此外，停药后她的症状和心脏功能恢复。
我们报告了一名患者在完成5个周期的地西他滨/西扎珠苷治疗后出现可逆性心肌病，该口服联合疗法旨在提高地西他滨的口服生物利用度，从而限制其不良反应。由于地西他滨/西扎珠苷联合疗法因其方便的口服制剂而越来越受欢迎，因此需要更多试验来了解该药物导致心肌病的发生率，并发现预防心脏毒性作用的策略。
Zotero 插件