The New England journal of medicine
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Randomized Controlled Trial Multicenter Study
Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.
The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). ⋯ Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those receiving placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT01958021 .).
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Randomized Controlled Trial
Acute Neurologic Disorder from an Inhibitor of Fatty Acid Amide Hydrolase.
Background A decrease in fatty acid amide hydrolase (FAAH) activity increases the levels of endogenous analogues of cannabinoids, or endocannabinoids. FAAH inhibitors have shown analgesic and antiinflammatory activity in animal models, and some have been tested in phase 1 and 2 studies. In a phase 1 study, BIA 10-2474, an orally administered reversible FAAH inhibitor, was given to healthy volunteers to assess safety. ⋯ One patient remained asymptomatic. Conclusions An unanticipated severe neurologic disorder occurred after ingestion of BIA 10-2474 at the highest dose level used in a phase 1 trial. The underlying mechanism of this toxic cerebral syndrome remains unknown.