Division of Hematology/Oncology, Tufts Medical Center, Boston, MA, USA.
Department of Pharmacy, The University of Arizona Cancer Center, Tucson, AZ, USA.
J Oncol Pharm Pract. 2021 Apr;27(3):658-672. doi: 10.1177/1078155220973737. Epub 2020 Nov 20.
Acute myeloid leukemia (AML) is primarily a disease of older adults. These patients may not be candidates for intensive treatment, and there has been an ongoing need for treatment options for this group. We review the use of glasdegib, a hedgehog-pathway inhibitor available for use in combination with low-dose cytarabine (LDAC). PubMed and relevant congress abstracts were searched using the term "glasdegib". In addition, based on our experience with glasdegib, we considered treatment aspects of particular relevance to pharmacists and advanced practitioners. In a randomized phase II study, the combination of glasdegib plus LDAC demonstrated superior overall survival versus LDAC alone (hazard ratio 0.51, 80% confidence interval 0.39-0.67, = 0.0004). The trial reported adverse events (AEs) of special relevance for older patients, such as hematologic events, gastrointestinal toxicity, and fatigue, as well as AEs associated with Hh-pathway inhibitors (alopecia, muscle spasms, dysgeusia). Educating patients about typical AEs can facilitate adherence as well as early AE identification and proactive management. For LDAC, which is a long-established therapy in AML, various stages of delivery need consideration, with attention to individual circumstances. Practical measures such as dispensing a longer supply can reduce the number of return clinic visits, providing a meaningful difference for many patients.
Pharmacists and advanced practitioners play important roles in treatment with glasdegib plus LDAC. Ultimately, framing plans for treatment delivery within the individual circumstances of each patient may enable them to stay on therapy longer, giving them the greatest potential to achieve benefit.
急性髓系白血病（AML）主要发生于老年人。这些患者可能不适合接受强化治疗，因此一直需要为这一群体提供治疗选择。我们回顾了 hedgehog 通路抑制剂吉西他滨与低剂量阿糖胞苷（LDAC）联合应用的相关数据。检索PubMed 和相关大会摘要时使用的术语为“glasdegib”。此外，根据我们使用 glasdegib 的经验，我们考虑了药师和高级从业者特别关注的治疗相关内容。在一项随机的 II 期研究中，glasdegib 联合 LDAC 相较于 LDAC 单药治疗显示出更好的总生存期（风险比 0.51，95%置信区间 0.39-0.67，P=0.0004）。该试验报告了一些对老年患者特别重要的不良事件（AE），如血液学事件、胃肠道毒性和疲劳，以及与 hedgehog 通路抑制剂相关的 AE（脱发、肌肉痉挛、味觉障碍）。向患者教育典型 AE 可以促进患者的依从性，同时还可以更早地识别和主动管理 AE。对于 LDAC，作为 AML 的一种长期确立的治疗方法，需要考虑其各个阶段的应用，同时关注患者的个体情况。例如，提供更长的药物供应可以减少患者返回诊所的次数，这对许多患者来说是一个有意义的差异。
药师和高级从业者在 glasdegib 联合 LDAC 治疗中发挥着重要作用。最终，在每位患者的个体情况下制定治疗方案可以使他们更长时间地接受治疗，从而最大程度地提高获益的可能性。
