Expert review of clinical pharmacology
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Expert Rev Clin Pharmacol · Jun 2018
ReviewGemtuzumab ozogamicin for the treatment of acute myeloid leukemia.
Gemtuzumab ozogamicin (GO) is an antibody-drug conjugate consisting of a monoclonal antibody targeting CD33 linked to a cytotoxic derivative of calicheamicin. Despite the known clinical efficacy in relapsed/refractory acute myeloid leukemia (AML), GO was withdrawn from the market in 2010 due to increased early deaths witnessed in newly diagnosed AML patients receiving GO + intensive chemotherapy. In 2017, new data on the clinical efficacy and safety of GO administered on a fractionated-dosing schedule led to re-approval for newly diagnosed and relapsed/refractory AML. ⋯ Expert commentary: GO represents the first drug-antibody conjugate approved (twice) in the United States for AML. Its re-emergence adds a valuable agent back into the armamentarium for AML. The approval of GO as well as three other agents for AML in 2017 highlights the need for rapid cytogenetic and molecular characterization of AML and incorporation into new treatment algorithms.
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Expert Rev Clin Pharmacol · Apr 2018
ReviewPD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that lacks durable responses to traditional chemotherapy. Areas covered: After MCC was shown to be an immunogenic tumor, small trials revealed high objective response rates to PD-1/PD-L1 checkpoint inhibitors. The JAVELIN Merkel 200 (NCT02155647) trial tested the use of avelumab, a human IgG1 monoclonal antibody against PD-L1, in metastatic MCC. ⋯ Additional studies will assess the utility and safety of adjuvant checkpoint blockade in patients with excised MCC. How to increase response rates by combining PD-1/PD-L1 blockade with other treatment approaches needs to be explored. In addition, treatment options for MCC patients who fail or do not respond to avelumab need to be identified.
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Until recently considered as a minor health problem, the role of bronchiectasis is now increasingly recognized. New specific drugs are being approved for treatment of bronchiectasis. Possibly they will offer better perspectives to bronchiectatic subjects with evolving course. ⋯ Macrolides are a currently preferred option. Inhaled antibiotics are gaining importance and are the object of ongoing research interest. Practical challenges of inhaled antibiotic treatment remain the need of defining the best therapeutic regimen and optimizing true adherence.
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Expert Rev Clin Pharmacol · Nov 2017
ReviewPimavanserin, a novel antipsychotic for management of Parkinson's disease psychosis.
Parkinson's disease psychosis (PDP) may develop in up to 60% of Parkinson's patients and is associated with increased morbidity and mortality. It also correlates with depression and dementia, and can contribute to caregiver stress and burnout. Pimavanserin is the first FDA approved drug for the treatment of hallucinations and delusions associated with PDP. ⋯ Expert commentary: Pimavanserin, a 5HT2A receptor inverse agonist, is the first FDA approved drug for the treatment of PDP which has been shown to reduce psychosis in PD through its unique mechanism of action. Pimavanserin, does not worsen PD motor symptoms and has an acceptable safety profile. The development of pimavanserin as an antipsychotic opened a new therapeutic avenue in the treatment of PDP as well as targeting psychosis in other disorders such as Alzheimer's disease.
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Expert Rev Clin Pharmacol · Nov 2017
ReviewTo which extent can we decrease antibiotic duration in critically ill patients?
Inadequate empirical antibiotic therapy is associated with higher mortality in critically ill patients with severe infections. Nevertheless, prolonged duration of antibiotic treatment is also potentially harmful. Development of new infections with more resistant pathogens is one of the arguments against the administration of prolonged courses of antibiotics. ⋯ We summarize the available information about the optimal duration of antimicrobial therapy in critically ill patients with severe infections including community-acquired pneumonia, intra-abdominal infections, bacteremia, meningitis and urinary-tract infections as well as the clinical consequences of short antimicrobial courses in certain severe infections. The utility of procalcitonin to reduce the duration of antibiotics is also discussed. Finally, we give clear recommendations about the length of treatment for the most common infections in critically ill patients.