The abundance of orally formulated chemotherapy agents reflects the expanding role of oral chemotherapy in the care of patients with cancer. Many oral chemotherapy agents have been used for a number of years, and several have been developed recently. Newer agents include the prodrugs capecitabine and temozolomide, the retinoid bexarotene, the immunomodulatory agent thalidomide, the protein kinase inhibitor imatinib, and the epidermal growth factor receptor inhibitors gefitinib and erlotinib. Each agent has unique pharmacologic properties, dosing, and side-effect profiles. This article reviews these agents from a pharmacology perspective.
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Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.
N Engl J Med
January 2025
From Médecins Sans Frontières (L.G., F.V.), Sorbonne Université, INSERM Unité 1135, Centre d'Immunologie et des Maladies Infectieuses (L.G.), Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Universitaire Sorbonne Université, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (L.G.), and Epicentre (M.G., E. Baudin), Paris, and Translational Research on HIV and Endemic and Emerging Infectious Diseases, Montpellier Université de Montpellier, Montpellier, Institut de Recherche pour le Développement, Montpellier, INSERM, Montpellier (M.B.) - all in France; Interactive Development and Research, Singapore (U.K.); McGill University, Epidemiology, Biostatistics, and Occupational Health, Montreal (U.K.); UCSF Center for Tuberculosis (G.E.V., P.N., P.P.J.P.) and the Division of HIV, Infectious Diseases, and Global Medicine (G.E.V.), University of California at San Francisco, San Francisco; the National Scientific Center of Phthisiopulmonology (A.A., E. Berikova) and the Center of Phthisiopulmonology of Almaty Health Department (A.K.), Almaty, and the City Center of Phthisiopulmonology, Astana (Z.D.) - all in Kazakhstan; Médecins Sans Frontières (C.B., I.M.), the Medical Research Council Clinical Trials Unit at University College London (I.M.), and St. George's University of London Institute for Infection and Immunity (S.W.) - all in London; MedStar Health Research Institute, Washington, DC (M.C.); Médecins Sans Frontières, Mumbai (V. Chavan), the Indian Council of Medical Research Headquarters-New Delhi, New Delhi (S. Panda), and the Indian Council of Medical Research-National AIDS Research Institute, Pune (S. Patil) - all in India; the Centre for Infectious Disease Epidemiology and Research (V. Cox) and the Department of Medicine (H. McIlleron), University of Cape Town, and the Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine (S.W.) - both in Cape Town, South Africa; the Institute of Tropical Medicine, Antwerp, Belgium (B. C. J.); Médecins Sans Frontières, Geneva (G.F., N.L.); Médecins Sans Frontières, Yerevan, Armenia (O.K.); the National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia (N.K.); Partners In Health (M.K.) and Jhpiego Lesotho (L.O.) - both in Maseru; Socios En Salud Sucursal Peru (L.L., S.M.-T., J.R., E.S.-G., D.E.V.-V.), Hospital Nacional Sergio E. Bernales, Centro de Investigacion en Enfermedades Neumologicas (E.S.-G.), Hospital Nacional Dos de Mayo (E.T.), Universidad Nacional Mayor de San Marcos (E.T.), and Hospital Nacional Hipólito Unanue (D.E.V.-V.) - all in Lima; Global Health and Social Medicine, Harvard Medical School (L.L., K.J.S., M.L.R., C.D.M.), Partners In Health (L.L., K.J.S., M.L.R., C.D.M.), the Division of Global Health Equity, Brigham and Women's Hospital (K.J.S., M.L.R., C.D.M.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, (L.T.), and Harvard T.H. Chan School of Public Health (L.T.) - all in Boston; and the Indus Hospital and Health Network, Karachi, Pakistan (H. Mushtaque, N.S.).
Background: For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis.
Methods: We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z).
First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial.
J Clin Oncol
January 2025
Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Chinese University of China, Shatin, Hong Kong Special Administrative Region, China.
Purpose: Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2: ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of ex20ins+ advanced/metastatic NSCLC.
View Article and Find Full Text PDFQuality assessment of clinical guidelines in the care of laryngitis and pharyngitis according to AGREE II.
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Departamento de Farmácia, Universidade de Brasília - UnB - Brasília (DF), Brasil.
Purpose: The study aimed to identify and assess the methodological quality of essential clinical guidelines for the management of laryngitis and pharyngitis.
Methods: A systematic search of clinical guidelines for the management of laryngitis and pharyngitis was performed in three databases. Methodological quality was assessed according to AGREE II, in which each item in its domains was scored by four independent evaluators.
New PPARα Agonist A190-Loaded Microemulsion for Chemotherapy-Induced Peripheral Neuropathy.
Mol Pharm
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Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of anticancer agents with limited effective preventive or therapeutic interventions. Although fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, has demonstrated neuroprotective and analgesic properties, its clinical utility is hindered by low receptor affinity, poor subtype selectivity, and suboptimal bioavailability. A190, a highly selective and potent nonfibrate PPARα agonist, offers a promising alternative but is limited by poor aqueous solubility, resulting in reduced oral bioavailability and therapeutic efficacy.
View Article and Find Full Text PDFEarly-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models.
Sci Transl Med
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University of Strasbourg, INSERM, Strasbourg Translational Neuroscience & Psychiatry STEP-CRBS, UMR-S 1329, 67000 Strasbourg, France.
Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS). This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic and mutation carriers exhibited increased wakefulness and reduced non-rapid eye movement sleep.
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