Drugs of today
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Lorlatinib is a novel third-generation tyrosine kinase inhibitor (TKI) which targets anaplastic lymphoma kinase (ALK) as well as receptor tyrosine kinase c-ros oncogene 1 (ROS1). A critical limitation of conventional ALK/ROS TKIs is their association with acquired resistance mutations (particularly ALK G1202R and ROS1 G2032R) in the ALK or ROS1 gene, although these are not the only resistance mechanisms. Another limitation of this class of drugs is their inadequate efficacy against central nervous system metastasis, likely attributable to the blood-brain barrier (BBB). ⋯ In September 2018, Japan became the first country where lorlatinib received approval for treating patients with ALK-rearranged non-small cell lung cancer. Eventually, the FDA approved lorlatinib (Lorbrena; Pfizer) in November 2018. Lorlatinib use is expected to increase in importance, owing to its promising efficacy in clinical trials.
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Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder typically caused by mutations in genes for lipoprotein lipase (LPL), apolipoprotein C-II (Apo-CII), apolipoprotein A-V (Apo-AV), lipase maturation factor 1 (LMF1) and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1). FCS is associated with severe morbidity that includes recurrent pancreatitis and other problems. Effective treatment to reliably prevent complications has been unavailable, so there is a quest to identify novel interventions to achieve sustained triglyceride lowering and prevention of pancreatitis. ⋯ It is being developed for treatment of patients with FCS and refractory hypertriglyceridemia. Data from a variety of clinical trials have been very encouraging, with documentation of excellent triglyceride-lowering efficacy, but there have been concerns about the risk of drug-related thrombocytopenia and bleeding that contributed to the recent decision by the Food and Drug Administration (FDA) to not approve the drug for clinical use. Clinical trials testing the safety and efficacy of volanesorsen are ongoing, so there is hope that the drug ultimately will be approved and available for treatment of high-risk patients with FCS.
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Patients with recurrent, nonmetastatic prostate cancer after curative intent therapy can experience a heterogeneous clinical course ranging from indolent disease that can be observed for years to a rapidly progressive disease that is metastatic in a relatively short time. Patients with short prostate-specific antigen (PSA) doubling times are at risk for early development of metastatic disease and are frequently placed on androgen deprivation therapy. ⋯ Apalutamide is a nonsteroidal antiandrogen agent that binds directly to the ligand-binding domain of the androgen receptor, preventing androgen receptor translocation, DNA binding and androgen receptor-mediated transcription. Apalutamide showed improved metastasis-free survival and prolonged time to symptomatic progression in men with nonmetastatic castration-resistant prostate cancer with a short PSA doubling time.
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Carcinoid tumors are rare and usually slow-growing. Some patients with advanced metastatic disease however can develop symptoms of carcinoid syndrome, which results in debilitating diarrhea and flushing. Many treatments including chemotherapy were tried unsuccessfully in the past to treat this syndrome. ⋯ The discovery that the production of this hormone can be inhibited by somatostatin led to the development of somatostatin analogues octreotide and lanreotide, which differ from native somatostatin in that they have a longer half-life. These compounds have shown dramatic responses in symptom control and reduction of serotonin metabolites including urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. This review researches the origins of carcinoid tumors, the development of lanreotide as a treatment and future directions for the treatment of carcinoid syndrome.
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The opioid pain market is a lucrative one, but is experiencing significant challenges in the U. S. as the country grapples with prescription opioid addiction, overdose and fatalities. ⋯ The development of abuse-deterrent prescription opioids is one such measure, but although abuse-deterrent formulations of opioids reduce drug liking and abuse, concerns have been highlighted by an Institute of Clinical and Economic Review (ICER) report regarding the insufficiency of currently available data to determine the effects of these formulations at the population level. However, the low abuse liability but effective analgesic efficacy reported for drugs such as NKTR-181 and difelikefalin highlight the potential of novel abuse-deterrent opioids.