Glasdegib plus low-dose cytarabine for acute myeloid leukemia: Practical considerations from advanced practitioners and pharmacists.

OBJECTIVE: 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).Data Sources: 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.Data Summary: 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, p = 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. CONCLUSIONS: 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.

Paradoxical effect of capecitabine in 5-fluorouracil-induced cardiotoxicity: A case vignette and literature review.

5-fluorouracil is a chemotherapeutic agent that plays an important role in the treatment of various cancers including head and neck and gastrointestinal malignancies. Therapy with 5-fluorouracil is rarely associated with cardiotoxic effects including angina, heart failure, myocardial infarction and cardiac arrest, resulting in discontinuation at the expense of sub-optimal treatment of the targeted malignancy. In this article, we review the literature reported on 5-fluorouracil-associated cardiotoxicity and present a case of a patient who experienced chest pain on 5-fluorouracil. The cardiac symptoms subsided after initiation of capecitabine, the oral formulation of 5-fluorouracil. To our knowledge, this is only the second reported case where 5-fluorouracil was successfully replaced by capecitabine without recurrence of cardiac symptoms. Capecitabine may be a viable option for patients who develop 5-fluorouracil-induced chest pain. However, large clinical trials are warranted to confirm these findings. Currently, there is insufficient evidence to recommend an optimal approach for safe and effective alternative treatment for patients who experience 5-fluorouracil-induced cardiac adverse events.

The use of brincidofovir for the treatment of mixed dsDNA viral infection.

Double-stranded DNA (dsDNA) viral infections constitute a major complication following solid organ and stem cell transplantation. Few therapeutic options are currently available for the treatment of such infections in highly immunocompromised hosts. Brincidofovir is an oral investigational drug with broad antiviral activity against dsDNA viruses in vitro, but clinical experience is limited. Here we report a young female who developed a mixed infection with adenovirus, cytomegalovirus, Epstein-Barr virus and BK polyomavirus after an allogeneic stem cell transplant, and was successfully treated with brincidofovir.

Overview of Pharmacological Treatment Options for Pediatric Patients with Refractory Kawasaki Disease.

Kawasaki disease is an autoimmune disease found predominantly in children under the age of 5 years. Its incidence is higher in those who live in Asian countries or are of Asian descent. Kawasaki disease is characterized as an acute inflammation of the vasculature bed affecting mainly the skin, eyes, lymph nodes, and mucosal layers. Although the disease is usually self-limiting, patients may develop cardiac abnormalities that can lead to death. The exact cause of the disease is unknown; however, researchers hypothesize that an infectious agent is responsible for causing Kawasaki disease. Initial treatment options with intravenous immune globulin and aspirin are sufficient to cure most patients who acquire this disease. Unfortunately, in up to one-quarter of patients, the disease will be refractory to initial therapy and will require further management with corticosteroid, immunomodulatory, or cytotoxic agents. The lack of randomized, controlled trials makes treatment of refractory disease difficult to manage. Until larger randomized, controlled trials are published to give more guidance on therapy for this stage of disease, clinicians should use the data available from observational studies and case reports in conjunction with their clinical expertise to make treatment decisions.