Expert review of clinical pharmacology
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Introduction: Advanced cancers that did not respond to chemotherapy were once a death sentence, but now there are newer therapies utilizing the patient's own immune system to fight cancer that are proving effective in chemotherapy-refractory malignancies. However, this success against cancer cells may be accompanied by immune-related adverse events that can affect the kidneys. Areas covered: Using Medline and Scopus, we compiled all publications through February 2019 that pertained to immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor T-cells (CAR T-cells). The focus of this review is the discussion of these new cancer therapies, with attention to the reported kidney-related adverse effects.. ⋯ These self-protective mechanisms have been appropriated by tumor cells as a means of evading immune detection and destruction. New immunotherapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy incite an aggressive immune response directed against tumor cells. This unrestrained activation of the immune system may result in kidney injury via multiple mechanisms.
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Expert Rev Clin Pharmacol · Mar 2019
Review Comparative StudyEncorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations.
Combination treatment with a BRAF inhibitor and MEK inhibitor is the standard of care for patients with advanced BRAFV600 mutation-positive melanoma. With the currently available combinations of dabrafenib plus trametinib and vemurafenib plus cobimetinib, median progression-free survival (PFS) of over 12 months has been achieved. However, treatment resistance and disease recurrence remain a clinical challenge. ⋯ This improved efficacy may be related to the distinct pharmacokinetics of encorafenib, with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class. Increased specificity of encorafenib may also result in better tolerability with less off-target effects, including reduced occurrence of pyrexia and photosensitivity. Encorafenib plus binimetinib seems likely to emerge as a valuable therapeutic alternative to established BRAF/MEK inhibitor combinations.
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Expert Rev Clin Pharmacol · Mar 2019
ReviewLorlatinib for the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer.
Approximately 3-5% of patients with non-small cell lung cancer （NSCLC）belonged to anaplastic lymphoma kinase (ALK)-positive NSCLC. The treatment drugs of ALK-positive NSCLC mainly included crizotinib, ceritinib, alectinib, and brigatinib. Although these drugs had some effects, most of them were usually easy to develop drug resistance. ⋯ Lorlatinib could also pass through the blood-brain barrier, which had a good effect on patients with brain metastasis. Adverse events of lorlatinib were mostly mild and moderate in severity, and patients were easily tolerated. Most common adverse events were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea.
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Expert Rev Clin Pharmacol · Feb 2019
Review Meta AnalysisA meta-analysis of naldemedine for the treatment of opioid-induced constipation.
Opioid-induced constipation (OIC) is a common adverse effect in patients under long-term opioid therapy. Naldemedine is a novel peripherally acting μ-opioid receptor antagonists being developed for the treatment of OIC without affecting central analgesia. This meta-analysis is to assess the current evidence for efficacy and safety of naldemedine for the treatment of OIC. ⋯ The incidence of serious adverse effects (AEs) in naldemedine group was higher than placebo, especially in cancer patient subgroup. The AEs occurred in participants with naldemedine were mild to moderate and well tolerated during treatment. The results of this network meta-analysis will guide the future researchers in evaluating naldemedine for the treatment of OIC.
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Expert Rev Clin Pharmacol · Jan 2019
ReviewNeurologic conditions and disorders of uremic syndrome of chronic kidney disease: presentations, causes, and treatment strategies.
Introduction: Uremic syndrome of chronic kidney disease (CKD) is a term used to describe clinical, metabolic, and hormonal abnormalities associated with progressive kidney failure. It is a rapidly growing public health problem worldwide. Nervous system complications occur in every patient with uremic syndrome of CKD. ⋯ They include (1) accumulation of uremic toxins resulting in neurotoxicity, blood-brain barrier injury, neuroinflammation, oxidative stress, apoptosis, brain neurotransmitters imbalance, ischemic/microvascular changes, and brain metabolism dysfunction (e.g. dopamine deficiency), (2) metabolic derangement (as acidosis, hypocalcemia, hyperphosphatemia, hypomagnesemia, and hyperkalemia); (3) secondary hyperparathyroidism, (4) erythropoietin and iron deficiency anemia, (5) thiamin, vitamin D, and other nutritional deficiencies, (6) hyperhomocysteinemia, and (7) coagulation problems. Expert commentary: Nervous system complications of uremia contribute to the patients' morbidity and mortality. Optimizing renal replacement therapy, correction of associated metabolic and medical conditions, and improved understanding of possible pathogenic mechanisms of these complications is a major target for their prevention and treatment.