Extemporaneous compounding of dabrafenib and trametinib for cancer patients with feeding tubes.

INTRODUCTION: Dabrafenib and trametinib are oral targeted agents indicated for BRAF mutated non-small cell lung cancer and melanoma. There is little data to support the administration of these two agents via enteral feeding tube. This case series describes three patients who received compounded dabrafenib and trametinib suspensions through enteral feeding tubes. CASE REPORT: We present three patients who required dabrafenib and trametinib to be prepared as a non-standard compound for the medications to be administered via feeding tube. The patients were diagnosed with with BRAF mutated cancers including melanoma, non-small-cell lung carcinoma, and anaplastic thyroid cancer. In all three cases, there was evidence of initial disease response on imaging, and there were no unexpected toxicities secondary to dabrafenib and trametinib. DISCUSSION: There are patients that are unable to tolerate medications by mouth due to dysphagia, anatomical malfunctions, or other digestive disorders. There is limited literature that describes preparation of trametinib and dabrafenib into an enteral suspension. Identifying a safe and efficacious method of administering these two medications via feeding tube ensures that these patients continue to be able to receive them as part of their anti-cancer therapy. CONCLUSION: Despite the lack of available data, compounding of dabrafenib and trametinib may be clinically appropriate when benefits outweigh the risk of unconventional administration. Further studies are warranted to assess for the pharmacokinetics, pharmacodynamics, stability, and storage for these liquid medications.

Management of Steroid-Refractory Gastrointestinal Immune-Related Adverse Events.

BACKGROUND: Immune checkpoint inhibitors (ICIs) cause inflammatory immune-related adverse events (irAEs), which are often effectively managed with steroids. Less is known about the best management of irAEs refractory to steroid treatment. OBJECTIVE: We aimed to assess the efficacy of second-line medications used to treat gastrointestinal (GI) irAEs. METHODS: This study was a single-center, retrospective medical record review of patients who received steroids for an ICI GI irAE and at least one dose of infliximab, vedolizumab, or adalimumab for irAE treatment from March 25, 2011 to September 20, 2019, approved by Yale University's Institutional Review Board. Our primary objective was to assess the efficacy of second-line treatment, measured by the change in the Common Terminology Criteria for Adverse Events Version 5.0 grading system. RESULTS: A total of 39 patients met inclusion criteria. Treatment for steroid-refractory GI irAEs demonstrated a high response rate, with irAE resolution seen in 89.7% of patients. Patients who were specifically initiated on infliximab within 14 days of starting steroids had a higher percent resolution seen in 94.4% of patients. The average time to response, defined as the average days from second-line therapy to reported symptom resolution, was 17 days. CONCLUSION AND RELEVANCE: Steroid-refractory GI irAEs can be managed effectively in most patients with immunosuppressive therapy, such as infliximab. Furthermore, initiating second-line immunosuppressive therapy within 14 days of steroid failure resulted in a higher rate of symptom resolution.

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab.

INTRODUCTION/BACKGROUND: Durvalumab is a programmed cell death ligand 1 (PD-L1) inhibitor indicated for stage III, unresectable non-small cell lung cancer (NSCLC) consolidation therapy following concurrent platinum-based chemoradiation based on results of the PACIFIC trial. Safety data of durvalumab demonstrates an increased risk of immune-related adverse effects (irAEs), most notably pneumonitis. Pneumonitis is a serious and potentially fatal complication of immunotherapy. It is important to investigate the incidence of pneumonitis in clinical practice to evaluate the generalizability of published data. The objective of this study is to assess and characterize real-world incidence of pneumonitis in patients with NSCLC receiving durvalumab. MATERIALS AND METHODS: This retrospective study included patients who were initiated on durvalumab for unresectable stage III NSCLC from February 2018 through November 2019. The data analysis utilized descriptive statistics to determine the incidence of pneumonitis associated with durvalumab. RESULTS: Of the 83 patients who were evaluated, 21 patients (25.3%) experienced pneumonitis, with 5 cases (6%) being grade 3/4. Seven patients were re-challenged with durvalumab, while 14 patients permanently discontinued durvalumab. There were no clearly identifiable risk factors leading to an increased incidence of pneumonitis. CONCLUSION: The results of this study indicate that real-world incidence of pneumonitis in stage III NSCLC patients receiving durvalumab consolidation therapy is congruent with the incidence reported in the PACIFIC trial.

Etoposide phosphate for pediatric orthopedic malignancies after intravenous etoposide hypersensitivity.

BACKGROUND: Hypersensitivity reactions to etoposide have been reported and patients have been safely transitioned to etoposide phosphate for continued therapy. However, the safety and efficacy of substituting etoposide phosphate for etoposide has not been well established in pediatric orthopedic malignancies. The aim of this study is to determine whether etoposide phosphate can be substituted for etoposide in pediatric orthopedic malignancies. METHODS: A chart review of pediatric patients who developed hypersensitivity reactions to etoposide while being treated for orthopedic malignancies was performed at a large academic medical center. Three patients were identified, two with Ewing sarcoma and one with an osteosarcoma. All three patients experienced hypersensitivity reactions to their first doses of etoposide and were switched to etoposide phosphate for further therapy. RESULTS: After premedication, all three patients tolerated full doses of etoposide phosphate without a graded dose challenge or desensitization. Two of the patients were premedicated with diphenhydramine alone, while the third received diphenhydramine and dexamethasone. CONCLUSIONS: Etoposide phosphate is a potentially safe alternative for pediatric patients with orthopedic malignancies who experience etoposide hypersensitivity. However, caution is needed as there are cases of etoposide phosphate hypersensitivity.

Lorcaserin: a novel serotonin 2C agonist for the treatment of obesity.

BACKGROUND: Obesity has become an epidemic in the United States and its prevalence continues to increase. Adjunctive treatment with pharmacotherapy is often reserved for individuals who fail to achieve their intended weight goals with diet and exercise alone. Current approved therapies for weight loss include phentermine, diethylpropion, orlistat, and phentermine/topiramate. The objective of this paper was to review the place of lorcaserin, a novel serotonin 2C agonist, which was FDA approved in July 2012. Unlike contemporary lipase inhibitors and sympathomimetic amines, lorcaserin is purported to reduce food consumption and increase satiety. SCOPE: A systematic review of the literature for all relevant articles was performed through January 2013 using MEDLINE, Web of Science, and International Pharmaceutical Abstracts using key words related to lorcaserin. FINDINGS: Three phase III clinical studies have been published evaluating the efficacy and safety of lorcaserin in various obese populations. A higher proportion of patients receiving lorcaserin (∼47%) lost more than 5% body weight from baseline in comparison with the placebo group (∼25%; p < 0.05 in all studies). Those receiving the recommended dose of lorcaserin 10 mg twice daily lost on average ∼6 kg of body weight from baseline versus ∼3 kg with placebo. Patients with diabetes mellitus also saw significant reductions in their HbA1c with lorcaserin (∼0.9%) versus placebo (∼0.4%; p < 0.001). Lorcaserin is generally well tolerated with the most commonly experienced adverse events being nausea, dizziness, headache, upper respiratory tract infections, and nasopharyngitis. Cardiovascular evaluations showed no appreciable increase in valvulopathy with lorcaserin use versus placebo. CONCLUSION: For now, pharmacists should continue to recommend the use of lorcaserin as a complement to, not in lieu of, ongoing lifestyle and behavioral modification.