Drugs
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Post-stroke lower limb spasticity impairs balance and gait leading to reduced walking speed, often increasing wheelchair use and caregiver burden. Several studies have shown that appropriate treatments for lower limb spasticity after stroke include injections of botulinum toxin type A (BoNT-A), phenol or alcohol, surgical correction and a rehabilitation program. In the present article, we review the safety and effectiveness of BoNT-A for the treatment of lower limb spasticity after stroke, with a focus on higher doses of BoNT-A. ⋯ Studies of high doses of BoNT-A also showed a greater reduction of severe post-stroke spasticity. In stroke survivors with spasticity of the ankle plantar-flexor muscles, a combined approach between surgery and BoNT-A can be indicated. However, controversy remains about improvement in motor function relative to post-stroke spasticity reduction after BoNT-A treatment.
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Larotrectinib (VITRAKVI®) is an orally administered, small molecule, highly-selective, tropomyosin receptor kinase (TRK) inhibitor that was developed by Loxo Oncology in collaboration with Bayer AG as a treatment for adult and paediatric patients whose cancers harbour neurotrophic receptor tyrosine kinase (NTRK) gene fusions. In November 2018 larotrectinib received its first global approval in the USA for the treatment of adult and paediatric patients with solid tumours that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. A registration application for the use of larotrectinib in paediatric and adult patients with locally advanced or metastatic solid tumours with NTRK gene fusion proteins has been submitted in the EU. This article summarizes the milestones in the development of larotrectinib leading to its first approval for the treatment of adult and paediatric patients with solid tumours that have NTRK gene fusion.
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Lorlatinib is an oral small molecule inhibitor of anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (ROS1) kinase developed by Pfizer for the treatment of ALK-positive non-small cell lung cancer (NSCLC). Based on results from a phase I/II trial, lorlatinib received approval in Japan in September 2018 and in the USA in November 2018 for the treatment of ALK-positive NSCLC. This article summarizes the milestones in the development of lorlatinib leading to the first global approval for this indication.
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Immune checkpoint blockade has revolutionised the treatment of multiple cancers including melanoma, non-small cell lung cancer, urothelial and renal cell cancers. For patients with chemorefractory gastroesophageal cancer, treatment with anti-PD-1 therapy results in modest benefits in overall survival; nivolumab and pembrolizumab have been licenced in Japan and the USA, respectively, for this indication. ⋯ Combining anti-PD-1 with cytotoxic chemotherapy and targeted therapies also shows promise to extend the benefit of immune checkpoint blockade to a larger proportion of gastroesophageal cancer patients. In this review we discuss recently reported and ongoing clinical research in immunotherapy for gastroesophageal cancer, and consider molecular biology associated with sensitivity and resistance to immune checkpoint blockade in gastroesophageal cancer patients.
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Paratek Pharmaceuticals are developing omadacycline (NUZYRA™), a first-in-class orally active aminomethylcycline antibacterial, as a treatment for various bacterial infections. The drug, which is available in intravenous and oral formulations, has a broad spectrum of antibacterial activity and was recently approved in the USA as a treatment for the treatment of community acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults. This article summarizes the milestones in the development of omadacycline leading to this first global approval for the treatment of CABP and ABSSSI.